title: The preparedness of emergency medical services against occupationally acquired communicable diseases in the prehospital environment in South Africa.

text: BACKGROUND Emergency medical care is performed in an uncontrolled environment and involves invasive procedures and life support measures. The performance of these duties places emergency care practitioners (ECPs) at risk of occupationally acquired injuries and communicable diseases. Although legislative guidelines exist for the protection of healthcare workers, little is known about the protective measures available for and utilised by ECPs in the pre-hospital environment in South Africa. OBJECTIVES To review the availability and implementation of emergency medical services (EMS)-specific infection control policies and standard operating procedures in the pre-hospital environment. METHODS Interviews with key informants were used to collect data concerning policies on communicable diseases and infection control in the EMS, the operational aspects of these policies, and educational programmes on communicable diseases and infection control for ECPs. RESULTS There is no national policy on communicable diseases and infection control in EMS. Only KwaZulu-Natal, Eastern Cape and Gauteng have EMS-specific standard operating procedures for communicable diseases and infection control. Formal education and in-service training is limited. CONCLUSIONS A national communicable disease and infection control policy specific to the EMS needs to be developed together with an accredited training module on communicable diseases and infection control for EMS in the pre-hospital environment.


Editorial: Spread of colds.


title: Expanding role for the apelin/APJ system in physiopathology.

text: Apelin is a bioactive peptide known as the ligand of the G protein-coupled receptor APJ. Diverse active apelin peptides exist under the form of 13, 17 or 36 amino acids, originated from a common 77-amino-acid precursor. Both apelin and APJ mRNA are widely expressed in several rodent and human tissues and have functional effects in both the central nervous system and peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular functions, fluid homeostasis, vessel formation and cell proliferation. More recently, apelin has been described as an adipocyte-secreted factor (adipokine), up-regulated in obesity. By acting as circulating hormone or paracrine factor, adipokines are involved in physiological regulations (fat depot development, energy storage, metabolism or eating behavior) or in the promotion of obesity-associated disorders (type 2 diabetes and cardiovascular dysfunctions). In this regard, expression of apelin gene in adipose tissue is increased by insulin and TNFalpha. This review will consider the main roles of apelin in physiopathology with particular attention on its role in energy balance regulation and in obesity-associated disorders.


title: Viral infection of the lungs through the eye.

text: Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.


title: Evaluation of reverse transcription-PCR assays for rapid diagnosis of severe acute respiratory syndrome associated with a novel coronavirus.

text: The reverse transcription (RT)-PCR protocols of two World Health Organization (WHO) severe acute respiratory syndrome (SARS) network laboratories (WHO SARS network laboratories at The University of Hong Kong [WHO-HKU] and at the Bernhard-Nocht Institute in Hamburg, Germany [WHO-Hamburg]) were evaluated for rapid diagnosis of a novel coronavirus (CoV) associated with SARS in Hong Kong. A total of 303 clinical specimens were collected from 163 patients suspected to have SARS. The end point of both WHO-HKU and WHO-Hamburg RT-PCR assays was determined to be 0.1 50% tissue culture infective dose. Using seroconversion to CoV as the "gold standard" for SARS CoV diagnosis, WHO-HKU and WHO-Hamburg RT-PCR assays exhibited diagnostic sensitivities of 61 and 68% (nasopharyngeal aspirate specimens), 65 and 72% (throat swab specimens), 50 and 54% (urine specimens), and 58 and 63% (stool specimens), respectively, with an overall specificity of 100%. For patients confirmed to have SARS CoV and from whom two or more respiratory specimens were collected, testing the second specimen increased the sensitivity from 64 and 71% to 75 and 79% for the WHO-HKU and WHO-Hamburg RT-PCR assays, respectively. Testing more than one respiratory specimen will maximize the sensitivity of PCR assays for SARS CoV.


title: The immunobiological and clinical role of vitamin D in obstructive lung diseases.

text: Vitamin D is a fat-soluble vitamin, which is obtained by conversion of 7-dehydrocholesterol in the skin by UV ray and by diet. Its role on bone mineralization has been known for over two hundred years, while its non-skeletal effects have been acknowledged only in the last few years. The discovery of important vitamin D properties on the innate and adaptive immune system created a lot of interest in a potential role of vitamin D on diseases characterized by heightened inflammation and oxidative response, and impaired antimicrobial response, such as asthma and chronic obstructive pulmonary disease (COPD). Recent studies have demonstrated that vitamin D and its deficiency have a number of biological effects which are potentially important in altering the pathogenesis and severity of both asthma and COPD. Vitamin D may improve lung function and response to steroids therapy, reduce airway remodeling and disease exacerbations. The aim of this study is to review the role of Vitamin D in asthma and COPD.


Early qualitative risk assessment of the emerging zoonotic potential of animal diseases.


title: Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents. The Group Health Medical Associates.

text: Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.


title: [Recommendations on bladder cancer Management during COVID-19 pandemia: lessons learned and future plans.]

text: OBJECTIVES The guidelines and recommendation sof good clinical practice have been disrupted by new and urgent policies, marked by the COVID-19 pandemic. Urothelial carcinoma has a significant prevalence in Spain, whose population has been greatly affected by COVID-19, directly by the disease and indirectly by the confinement. The objective of this work is to offer recommendations on protocols and guidelines adjusted to different phases of the pandemic. MATERIAL AND METHODS: This document on the management of bladder carcinoma is based on few evidence on urological oncological practice during the first months of the pandemic and on the authors' experience in this pathology during the crisis of COVID-19. Hospital experts in infectious disseases and radiology have participated to design a common strategy to reorganize the activity. RESULTS: Different proposals for treatment and follow-up of patients diagnosed with bladder cancer adjusted for oncological risk and the different phases of the pandemic are presented. CONCLUSIONS: The pandemic's spread was unimaginable just a few months ago. Health systems have been shaken by the disease in the most critical phases. It is necessary, at this time, to make an additional effort to develop tools that can facilitate the care of bladder carcinoma and minimize the impact and risks for patients and health professionals in the future.


title: Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill Adults.

text: OBJECTIVE To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults. DESIGN A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows. SETTING Medical ICU in a tertiary, academic medical center. PATIENTS Critically ill patients 18 years old or older. INTERVENTIONS Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation. MEASUREMENTS AND MAIN RESULTS Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator's previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95% CI, 0.82-5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy. CONCLUSIONS In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications.


title: Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family.

text: The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. The complex includes an RNA endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus, making it a genetic marker of this virus order. NendoU (nsp15) is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Neither biochemical nor sequence homology criteria allow a classification of nsp15 into existing endonuclease families. Here, we report the crystal structure of the severe acute respiratory syndrome coronavirus nsp15 at 2.6-A resolution. Nsp15 exhibits a unique fold and assembles into a toric hexamer with six potentially active, peripheric catalytic sites. The structure and the spatial arrangement of the catalytic residues into an RNase A-like active site define a separate endonuclease family, endoU, and represent another spectacular example of convergent evolution toward an enzymatic function that is critically involved in the coronavirus replication cycle.


title: Synthesis of novel test compounds for antiviral chemotherapy of severe acute respiratory syndrome (SARS).

text: This contribution reviews the synthesis of a range of experimental drugs designed for and aiming at antiviral chemotherapy of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)-induced human disease conditions. The selection of 25 test materials includes eleven trioxa-adamantane-triols (TATs) [BN, IBNCA, ABNCA, VANBA, ethylVANBA, euBN, euVANBA, ansaBN, Ehrlich BN, [6]prismaneBN, nitrodiBN], trivially termed bananins, one trioxa-adamantan-ol (TAO) THYMOBA, one bis-bananin pi-bananin (piBN), one triazaadamantane delta-bananin (deltaBN), seven potential nucleic acid-binding drugs (XBQC, INDO, PivINDO, AZTRION, AZADO, AZOCYS, AZOGALL), one potential antiviral interferon-inducer and distant nucleoside analog diazon, one potential HIV protein Vif antagonist AZODIAZON, one folic acid-diazon condensate DIAZONOFOL, and one special nucleoside analog (fructoinosine/fructovir). Four of the eleven bananins (BN, IBNCA, VANBA, euBN) were already demonstrated to constitute effective inhibitors of SARS-CoV NSP10/nsp13 RNA/DNA helicase/NTPase protein ATPase enzymatic function. Bananin (BN) was an effective inhibitor of both SARS-CoV RNA/DNA helicase nucleic acid unwinding function and SARS-CoV (Coronaviridae, Coronavirus) RNA-viral replication in cell culture. In summary, at least one selected compound of the synthesized test materials represents an interesting drug candidate for treatment of SARS-CoV-induced human disease (SARS). Viewed in aspects of organic chemistry [6]prismaneBN and nitrodiBN are the first true hexaprismane derivatives synthesized, and all reported compounds are entirely new.


title: Immunoglobulin A as an early humoral responder after mucosal avian coronavirus vaccination.

text: Infectious bronchitis virus (IBV) is a highly contagious coronavirus prevalent in all countries with an extensive poultry industry and continues to cause economic losses. IBV strains of the Ark serotype are highly prevalent in the Southeastern United States despite extensive vaccination. One explanation for this observation is the high genetic variability of IBV. In addition, IBV Ark-type vaccines may induce suboptimal mucosal immune responses, contributing to the prevalence and persistence of the Ark serotype. To test this hypothesis, chickens were ocularly vaccinated with a commercially available live attenuated IBV Ark-Delmarva Poultry Industry vaccine strain and both mucosal and systemic antibody responses were measured. The highest immunoglobulin A (IgA) spot-forming cell (SFC) response was observed in the Harderian glands (HG) and to a lesser extent in the spleen and conjunctiva-associated lymphoid tissues, while a limited IgG SFC response was observed in either the mucosal or systemic immune compartment. Interestingly, the peak IgA SFC response occurred 2 days earlier in spleen than in the head-associated lymphoid tissues despite ocular vaccination. Furthermore, IgA IBV-specific antibody levels significantly increased over controls 3 days earlier in tears and 4 days earlier in plasma than did IgG antibodies. IgA antibody levels were higher than IgG antibody levels throughout the primary response in tears and were similar in magnitude in plasma. In addition, a very early increase in IgA antibodies on day 3 postvaccination was observed in tears; such a response was not observed in plasma. This early increase is consistent with a mucosal T-independent IgA response to IBV. In the secondary response the IBV antibody levels significantly increased over controls starting on day 1 after boosting, and the IgG antibody levels were higher than the IgA antibody levels in both tears and plasma. In summary, ocular vaccination induced higher IgA antibodies in the primary IBV response, while the memory response is dominated by IgG antibodies. Thus, lower mucosal IgA antibody levels are observed upon secondary exposure to IBV, which may contribute to vulnerability of host epithelial cells to infection by IBV and persistence of the Ark serotype.


title: [Study on the correlation between positive rates of SARS RNA in clinical confirmed SARS patients and the appearance of RNA in relation to the development of the disease].

text: OBJECTIVES To study the correlation between positive rates of RNA in clinical confirmed severe acute respiratory syndrome (SARS) patients and its appearance in relation to the development of the disease in order to provide scientific basis for early diagnosis, effective prevention and treatment of the disease. METHODS One-step reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify the SARS RNA in the clinical specimens from different courses of the disease. The representative amplicons were then sequenced. Chi-square for trend test was performed to study the correlation between positive rates of RT-PCR and at different periods after the onset of the disease. RESULTS The fragments amplified from the sputum specimens of SARS patients were shown to share 100% homology with the published SARS-associated coronavirus. Of the different clinical specimens, positive rate in the stools appeared to be the highest (21.55%). Chi-square for trend test revealed that the positive rates of stools and sputa of SARS patients decreased with the development of the disease (chi(2) for trend = 12.55 and 16.408, P = 0.0004 and P = 0.000 05 respectively). CONCLUSION One-step RT-PCR proved to be an effective method for the detection of SARS-associated coronavirus from clinical specimens. Data as indicated that the positive rates of SARS coronavirus were decreasing in SARS patients along with the disease progression.


Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies.


docid: abpfvubf

title: Chlamydia screening among sexually active young female enrollees of health plans--United States, 1999-2001.

text: Chlamydia trachomatis infection is the most commonly reported sexually transmitted disease (STD) in the United States, with the highest rates among adolescent females and young women. Approximately 5%-14% of routinely screened females aged 16-20 years and 3%-12% of women aged 20-24 years are infected with chlamydia. Because up to 70% of chlamydial infections in women are asymptomatic, routine screening and treatment of infected persons is essential to prevent pelvic inflammatory disease, infertility, ectopic pregnancy, and perinatal infections. Since the 1990s, CDC, the U.S. Preventive Services Task Force, and several clinical organizations have recommended routine screening for chlamydial infection for all sexually active women aged <26 years and for pregnant women of all ages. To evaluate rates of chlamydia screening among sexually active young females, CDC analyzed 1999-2001 data from the Health Plan Employer Data and Information Set (HEDIS) reported by commercial and Medicaid health insurance plans. This report summarizes the results of that analysis, which determined that screening rates were low despite slight increases in screening covered both by commercial and Medicaid plans during 1999-2001. Increased screening by health-care providers and coverage of screening by health plans will be necessary to reduce substantially the burden of chlamydial infection in the United States.


title: Enteric pathogens in intensively reared veal calves.

text: Observations were made on development of diarrhea in special-fed calves (n = 460) on 8 commercial facilities during 2 successive 16-week production cycles at weeks 0, 2, 4, 8, 12, and 16. A total of 23% were affected, with peak number of calves with diarrhea observed at week 0. Suspected enteropathogens were identified in 86% of these calves, most commonly cryptosporidia, coronavirus, and rotavirus. Identified potential zoonotic pathogens included Giardia and Salmonella spp and verotoxigenic Escherichia coli. Noncytopathic bovine viral diarrhea virus was isolated from 6 calves that had repeated bouts of illness. Only 22% of calves entering the veal facilities had adequate transfer of passive immunity. At week 0, serum IgG concentration in calves that subsequently died or had diarrhea was lower (P < 0.001) than that in healthy calves. All calves that died (n = 6) during the first 4 weeks of production had complete failure of transfer of passive immunity.


title: Pathogenic relationships of rotavirus, Escherichia coli, and other agents in mixed infections in calves.

text: Infection with agents interpreted as causing or contributing to diarrhea (rotavirus, coronavirus, enterotoxigenic Escherichia coli, and cryptosporidia) were demonstrated in 24 of 32 newborn calves that had naturally occurring diarrheal disease. The calves were from 12 herds in Iowa. Infections as well as enteric lesions and hypoglobulinemia occurred more frequently among diarrheal calves than among nondiarrheal calves from these same herds. In most calves, infections were mixed; ie, both viruses, one or both viruses plus cryptosporidia, or rotavirus plus enterotoxigenic E coli.


What are the economic implications of COVID-19.


docid: zgkiauzj

title: Role of air distribution in SARS transmission during the largest nosocomial outbreak in Hong Kong.

text: UNLABELLED Severe acute respiratory syndrome (SARS) is primarily transmitted by bio-aerosol droplets or direct personal contacts. This paper presents a detailed study of environmental evidence of possible airborne transmission in a hospital ward during the largest nosocomial SARS outbreak in Hong Kong in March 2003. Retrospective on-site inspections and measurements of the ventilation design and air distribution system were carried out on July 17, 2003. Limited on-site measurements of bio-aerosol dispersion were also carried out on July 22. Computational fluid dynamics simulations were performed to analyze the bio-aerosol dispersion in the hospital ward. We attempted to predict the air distribution during the time of measurement in July 2003 and the time of exposure in March 2003. The predicted bio-aerosol concentration distribution in the ward seemed to agree fairly well with the spatial infection pattern of SARS cases. Possible improvement to air distribution in the hospital ward was also considered. PRACTICAL IMPLICATIONS Our study revealed the need for the development of improved ventilation and air-conditioning systems in an isolation ward or a general hospital ward for infectious respiratory diseases. The outbreak in Ward 8A, which was in a general hospital and could house nearly 40 patients, demonstrated the cross-infection risks of respiratory infectious diseases in hospitals if a potential highly infectious patient was not identified and isolated. Our example simulation, which extended the SARS Busters' design for an isolation room to Ward 8A, demonstrated that there was room for improvement to minimize cross-infection in large general hospital wards.


docid: eppzwzhw

title: Awareness of stroke warning signs--17 states and the U.S. Virgin Islands, 2001.

text: Stroke is the third leading cause of death in the United States and a major cause of disabilities among adults. Since 1900, the number of stroke deaths has declined, and substantial advances have been made in the diagnosis and treatment of ischemic stroke during the previous decade; however, the proportion of deaths that occur before patients are transported to hospitals has increased to nearly half of all stroke deaths. One of the national health objectives for 2010 is to increase the proportion of persons who are aware of the early warning symptoms and signs of stroke (objective no. 12.8). To assess public awareness and knowledge of the proper emergency response, CDC analyzed 2001 data from the Behavioral Risk Factor Surveillance System (BRFSS) in 17 states and the U.S. Virgin Islands (USVI). This report summarizes the results of that analysis, which indicated that public awareness of several stroke signs is high, but the ability to recognize the five major warning signs is low. Education campaigns are needed to increase public awareness of stroke signs and the necessity of calling 911 when persons are suffering a possible stroke.


title: Total mesorectal excision with radiofrequency in rectal cancer: open versus laparoscopy approach.

text: AIM The aim of this study was to compare the safety, efficacy and oncologic results in the low rectal resection with total mesorectal excision with radiofrequency (Ligasure™, Covidien, Boulder, CO, USA) in laparoscopic surgery. METHODS From July 2005 to December 2008, 227 patients underwent colorectal resection for cancer at S. Martino Hospital in Genoa. Sixty-one patients underwent curative rectal resection for mid or low rectal cancer using Ligasure™ device applied on smaller vessels and for the execution of total mesorectal excision. Forty-six patients underwent open laparotomy (OL), 15 laparoscopic surgery. There were no differences concerning demographics data and diagnosis, but only regarding staging (P=0.009). Primary goal was to evaluate major complications, operating time, hospital stay, distal margin of the tumor and number of nodes harvested in specimen. Secondary goal was to assess the average time of survival in the short period. RESULTS The mean operative times were shorter in the OL group (188 vs. 246 min) overall. This difference was significant (P=0.004). In particular two parameters of specimens were analyzed: the total number of nodes and distal clearing from cancer, excluding abdominoperineal resection. An average number of 16.6 nodes in the OL group and 13.9 in the VL group (P=ns) were detected; mean distal clearing in the OL group was 30.7 mm and 48.1 mm in the VL group (P=ns). There were no differences concerning major complications in either group. The hospital stay in the VL group was shorter than in the OL group, but the differences were not significant. CONCLUSION The Ligasure™ device does not reduce operating time in laparoscopy rectal cancer resection but it allows to get correct oncologic results in patients submitted to total mesorectal excision.


title: Canine viral enteritis.

text: Canine viral enteritis should be suspected in dogs with an acute onset of vomiting and diarrhea, especially in puppies and where several animals are affected simultaneously. Definitive diagnosis requires laboratory confirmation, most often detection of viral particles in the stool. No diagnostic test is entirely specific or absolutely sensitive, however, and laboratory findings should be weighed accordingly. Immunization is the key to successful control. Effective vaccines for canine parvovirus are available. Maternal antibody suppresses response to vaccination in young pups and is the major problem in the control of infection. Vaccines against canine rotavirus and coronavirus are not available. The need for such vaccines and the feasibility of their effective use have not yet been clearly demonstrated.


title: Current challenges in lower respiratory infections in children.

text: PURPOSE OF REVIEW Lower respiratory infections threaten the health of children worldwide. Streptococcus pneumoniae remains the most common bacterial cause of lower respiratory infection in children, whereas viral pathogens dominate as a more common cause of lower respiratory infection illness in infants and children overall. The diagnosis and clinical management of lower respiratory infections pose challenges to pediatric health providers as new technology is developed and new pathogens emerge in the spectrum of clinical disease. RECENT FINDINGS Human metapneumovirus is now recognized as a cause of lower respiratory infection disease in children, and coronavirus has been linked to epidemics of severe acute respiratory syndrome. Respiratory syncytial virus continues to be a major source of viral lower respiratory infection illness in children and can lead to childhood asthma. Treatment for respiratory syncytial virus bronchiolitis depends largely on the severity of disease and the course of clinical symptoms. The diagnosis of bacterial lower respiratory infection disease remains a clinical challenge, but new methods to detect S. pneumoniae, or Chlamydia pneumoniae and Mycoplasma pneumoniae may facilitate the clinical management of these illnesses. As immunization against S. pneumoniae becomes more widely used, the complications of bacterial lower respiratory infections will diminish markedly. SUMMARY Future progress in the clinical management of lower respiratory infection diseases will entail improved methods of early diagnosis, broader options for treatment, and better defined clinical parameters for triage and follow-up of children with lower respiratory infections.


title: Aberrant expression of CC and CXC chemokines and their receptors in patients with asthma.

text: This study further elucidates the roles of selected chemokines (IP-10, MIG, and RANTES) and their receptors (CCR3, CCR5, and CXCR3) in asthma. We compared their profiles in six groups of participants-atopic cohort and nonatopic cohort (each including controls and asthmatic patients with or without steroid therapy). Plasma concentration of IP-10 was significantly lower while that of RANTES and the expression of CCR3 were higher in asthmatic patients (all p < 0.05). Plasma RANTES correlated positively with the GINA severity score in all asthmatic patients (r=0.27, p < 0.05), and with IL-13 in nonatopic asthmatic patients (r=0.46, p < 0.05). In asthmatic patients, the ex vivo release of IP-10 and MIG was attenuated in PBMC activated with allergen, mitogens and IL-18 (p < 0.05). In conclusion, plasma RANTES may be a surrogate marker for asthma and the diminished Th1 related CXC chemokine production may contribute to Th2 predominance in asthma.


title: Prevalence of thermophilic Campylobacter species in cats and dogs in two animal shelters in Ireland.

text: Rectal swabs or faecal samples for the isolation of Campylobacter species were taken from 120 dogs and cats in an animal shelter in which only one kitten showed signs of gastrointestinal disease, and rectal swabs were taken from 46 dogs, 22 of which showed signs of gastrointestinal disease, in another shelter. At the first shelter, the swabs from 24 of 47 dogs (51.1 per cent) and 36 of 48 cats (75 per cent) yielded a Campylobacter species. The rate of isolation was significantly higher from dogs and cats less than six months old, and significantly higher from cats than from dogs (P< or =0.05). At the second shelter Campylobacter species were isolated from 40 of 46 dogs (87 per cent), but there was no significant difference between the age groups. Campylobacter species were isolated from 19 (86.4 per cent) of the 22 dogs with signs of gastrointestinal disease and from 21 (87.5 per cent) of the 24 unaffected dogs. Several culture methods were applied to the samples collected from both shelters, and the combination significantly increased the recovery of Campylobacter species.


title: [Morphological study of severe acute respiratory syndrome (SARS)].

text: OBJECTIVE Seven cases of autopsy from SARS patients are studied to investigate the pathogenesis and the pathologic changes of the major organs. METHODS Detailed gross and microscopic examination of the autopsy specimen is performed, including lung, heart, liver, kidney, spleen and lymph nodes. RESULTS All of the lungs are markedly enlarged and consolidated. Microscopically, pulmonary edema is a prominent finding, especially at the early stage of the disease (5 days after the onset). The alveolar spaces are filled with fibrinous exudates and lined with hyaline membrane. In 5 cases that undergo over 3 weeks of the course, the main pattern is organization of intra-alveolar deposit, along with fibroblastic proliferation in the alveolar septa, which leads to obliteration of alveolar space and pulmonary fibrosis. All of the lungs show bronchopneumonia, scattered hemorrhage, and proliferation of alveolar epithelial cells with desquamation. Microthrombi are seen in 6 cases. Fungal infection is noted in 2 cases. One of them is disseminative, involving bilateral lungs, heart, and kidney; the other one is diagnosed in hilar lymph nodes. In immune system, hilar and abdominal lymph nodes are usually congested and hemorrhagic, with depletion of lymphocytes, and accompanied with subcapsular sinus histiocytosis. One of the cases shows enlargement of abdominal lymph nodes, which have reduced number of germinal centers. Spleen exhibits atrophy of white pulps, and even lost of white pulps in some areas. The red pulp is markedly congested and hemorrhagic. In 5 cases, cardiomegale is prominent. Thrombosis (2 cases), focal myocarditis (1 case), and fungal myocarditis (1 case) are observed. In addition, liver shows massive necrosis (1 case) and nodular cirrhosis (1 case). CONCLUSIONS Lung is the major organ affected by SARS, demonstrated as diffuse alveolar damage. It is postulated that viral infection induces severe damage of alveolar epithelial and capillary endothelial cells, leads to pulmonary edema, intra-alveolar fibrin deposit, and hyaline membrane formation. Consequently, intra-alveolar organization and alveolar septal fibrosis causes loss of alveolar spaces, eventually, pulmonary fibrosis and atelectasis. The immune system is often affected, and presented as depletion of lymphoid tissue in lymph nodes and spleen. Secondary infection is a common complication, which should be paid close attention in the management of SARS patients.


title: [Coronaviruses in pathology].

text: The crown-like projections on the surface of the particles permits differentiation of coronaviruses from other riboviruses and their individualization as a distinct family. Recognition of their role in the aetiology of respiratory, enteral and encephalitic infections has promoted investigations for the finding of preventive vaccines. Selection of the strains showed that their immunogenicity depends upon the density and salience of the crown-like projections, the antigenic relationship of the projections determining cross serologic reactions between different species. At present experiments are being carried out on animals with vaccines prepared with antigenically related heterologous cornavirus species, not pathogenic for the host, and with subunitary vaccines prepared from the projections of the homologous species. The Coronaviridae family established on morphologic criteria is thus confirmed by the immunologic relationship and specificity of its members.


When isn't the cause of acute respiratory distress syndrome important?


title: Functional analysis of cell surface-expressed hepatitis C virus E2 glycoprotein.

text: Hepatitis C virus (HCV) glycoproteins E1 and E2, when expressed in eukaryotic cells, are retained in the endoplasmic reticulum (ER). C-terminal truncation of E2 at residue 661 or 715 (position on the polyprotein) leads to secretion, consistent with deletion of a proposed hydrophobic transmembrane anchor sequence. We demonstrate cell surface expression of a chimeric glycoprotein consisting of E2 residues 384 to 661 fused to the transmembrane and cytoplasmic domains of influenza A virus hemagglutinin (HA), termed E2661-HATMCT. The E2661-HATMCT chimeric glycoprotein was able to bind a number of conformation-dependent monoclonal antibodies and a recombinant soluble form of CD81, suggesting that it was folded in a manner comparable to "native" E2. Furthermore, cell surface-expressed E2661-HATMCT demonstrated pH-dependent changes in antigen conformation, consistent with an acid-mediated fusion mechanism. However, E2661-HATMCT was unable to induce cell fusion of CD81-positive HEK cells after neutral- or low-pH treatment. We propose that a stretch of conserved, hydrophobic amino acids within the E1 glycoprotein, displaying similarities to flavivirus and paramyxovirus fusion peptides, may constitute the HCV fusion peptide. We demonstrate that influenza virus can incorporate E2661-HATMCT into particles and discuss experiments to address the relevance of the E2-CD81 interaction for HCV attachment and entry.


title: [Diagnosis of bovine coronaviruses using mouse erythrocyte suspensions stabilized with formalin].

text: Bovine coronavirus isolated from calf faeces diseased with gastroenteritis and passaged to colostrum-free calves agglutinated mouse and rat erythrocytes. The agglutination reaction depended on temperature and took place only at a temperature of 4 degrees C. At a temperature of 37 degrees C the agglutinate broke down within 15 minutes. The coronavirus could be detected by the haemagglutination test in the contents of the small and large intestines and in the faeces of experimentally and naturally infected calves. The agglutination capacity of mouse erythrocytes was not affected by careful fixation of these erythrocytes with formalin and subsequent lyophilization and remained unchanged for as long as 52 weeks of storage at a temperature of 4 degrees C. It was demonstrated by a comparative examination of 182 samples of the faeces of calves suffering from diarrhoea that haemagglutination test was as sensitive as electron microscopy.


title: The silent revolution: RNA interference as basic biology, research tool, and therapeutic.

text: RNA interference (RNAi) is an evolutionarily conserved mechanism for silencing gene expression. In primitive organisms, RNAi protects the genome from viruses and other insertable genetic elements and regulates gene expression during development. The antisense (guide) strand of short double-stranded RNAs is incorporated into an RNA-induced silencing complex that can either suppress protein expression or direct degradation of messenger RNAs that contain homologous sequence(s). The discovery that RNAi works in mammalian cells has sparked intense investigation into its role in normal mammalian cell function, its use as a tool to understand or screen for genes functioning in cellular pathways in healthy and diseased cells and animals, and its potential for therapeutic gene silencing. RNAi may provide an important new therapeutic modality for treating infection, cancer, neurodegenerative disease, and other illnesses, although in vivo delivery of small interfering RNAs into cells remains a significant obstacle.


title: Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5'-triphosphatase activities.

text: The human coronavirus 229E (HCoV-229E) replicase gene-encoded nonstructural protein 13 (nsp13) contains an N-terminal zinc-binding domain and a C-terminal superfamily 1 helicase domain. A histidine-tagged form of nsp13, which was expressed in insect cells and purified, is reported to unwind efficiently both partial-duplex RNA and DNA of up to several hundred base pairs. Characterization of the nsp13-associated nucleoside triphosphatase (NTPase) activities revealed that all natural ribonucleotides and nucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed most efficiently. Using the NTPase active site, HCoV-229E nsp13 also mediates RNA 5'-triphosphatase activity, which may be involved in the capping of viral RNAs.


title: A serosurvey of viral infections in lions (Panthera leo), from Queen Elizabeth National Park, Uganda.

text: Serum samples from 14 lions (Panthera leo) from Queen Elizabeth National Park, Uganda, were collected during 1998 and 1999 to determine infectious disease exposure in this threatened population. Sera were analyzed for antibodies against feline immunodeficiency virus (FIV), feline calicivirus (FCV), feline herpesvirus 1 (feline rhinotracheitis: FHV1), feline/canine parvovirus (FPV/CPV), feline infectious peritonitis virus (feline coronavirus: FIPV), and canine distemper virus (CDV) or for the presence of feline leukemia virus (FeLV) antigens. Ten lions (71%) had antibodies against FIV, 11 (79%) had antibodies against CDV, 11 (79%) had antibodies against FCV, nine (64%) had antibodies against FHV1, and five (36%) had antibodies against FPV. Two of the 11 CDV-seropositive lions were subadults, indicating recent exposure of this population to CDV or a CDV-like virus. No lions had evidence of exposure to FeLV or FIPV. These results indicate that this endangered population has extensive exposure to common feline and canine viruses.


Inhaled Nebulized Sodium Pyruvate Use in COVID-19 Patients.


title: Influenza-associated pediatric deaths--United States, September 2010-August 2011.

text: Influenza-associated pediatric mortality has been a nationally notifiable condition since October 2004. This report summarizes the 115 cases of influenza-associated pediatric mortality reported to CDC that occurred from September 1, 2010, through August 31, 2011. Deaths occurred in 33 states. Nearly half of the deaths (46%) occurred in children aged <5 years. Of the children who died, 49% had no known Advisory Committee on Immunization Practices (ACIP)-defined high-risk medical conditions, and 35% died at home or in the emergency department. Of the 74 children aged ≥6 months for whom vaccination data were available, 17 (23%) had been fully vaccinated. ACIP recommends that all children aged ≥6 months receive vaccination against influenza annually. These findings underscore the importance of vaccinating children to prevent influenza virus infection and its potentially severe complications. Health-care providers should develop a comprehensive strategy to increase vaccination coverage among children.


title: A randomized controlled study of botulinum toxin A in the treatment of hemiplegic shoulder pain associated with spasticity.

text: OBJECTIVES To assess the effects of botulinum toxin A (BT-A) on hemiplegic shoulder pain associated with spasticity. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Outpatient clinic of a rehabilitation department. PARTICIPANTS Patients, more than three months post stroke, with hemiplegic shoulder pain associated with shoulder adductor and elbow flexor spasticity, randomly assigned to BT-A or placebo. INTERVENTION One-time injection of BT-A (500 units) into the pectoralis major and biceps brachii on the hemiplegic side. MAIN MEASURES Visual analogue scale of shoulder pain (0 -10), shoulder adductor and elbow flexor tone using the Ashworth Scale and passive range of shoulder abduction. These were assessed at baseline, four weeks, eight weeks and 12 weeks post injection. RESULTS Seventeen patients were enrolled, eight in the BT-A group and nine in the placebo group. At baseline, the median visual analogue scale score for shoulder pain was 6, the median Ashworth Scale shoulder adductor and elbow flexor spasticity score was 2 and the median range of shoulder abduction 76 degrees. Subjects who received BT-A showed significantly greater improvements in median shoulder adductor and elbow flexor Ashworth Scale scores than placebo at week 4 (P B / 0.01) but not at week 8 and 12. For shoulder pain and passive shoulder abduction range, all subjects showed postinjection improvements and no difference could be demonstrated between the two groups. DISCUSSION Possible reasons for the negative finding in this study include the small sample size and the presence of causes of shoulder pain not related to spasticity which could have confounded outcome.


title: Bluetongue in the United Kingdom and northern Europe in 2007 and key issues for 2008.

text: As predicted, bluetongue arrived in the UK in 2007. Here, John Gloster and colleagues investigate the meteorological parameters that allowed this incursion into the UK and discuss key issues related to the disease's possible re-establishment in 2008.


Erratum to: Alphacoronavirus in urban Molossidae and Phyllostomidae bats, Brazil.


title: Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders.

text: The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer's disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson's disease, and Huntington's chorea. The neuromodulatory actions at CB₁ receptors by endogenous agonists ('endocannabinoids'), of which anandamide and 2-arachidonoylglycerol are the two most studied representatives, allows them to counteract the neurochemical unbalances arising during these disorders. In contrast, the immunomodulatory effects of these lipophilic mediators at CB₂ receptors regulate the activity and function of glia and microglia. Indeed, the level of expression of CB₁ and CB₂ receptors or of enzymes controlling endocannabinoid levels, and hence the concentrations of endocannabinoids, undergo time- and brain region-specific changes during neurodegenerative and neuroinflammatory disorders, with the initial attempt to counteract excitotoxicity and inflammation. Here we discuss this plasticity of the endocannabinoid system during the aforementioned central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB₁ and CB₂ receptors for the treatment of the symptoms or progression of these diseases.


title: Quasispecies development by high frequency RNA recombination during MHV persistence.

text: Recent studies suggest that infectious viruses and particularly persisting viral RNAs often exist as diverse populations or "quasispecies". We have developed an approach to characterize populations of the murine coronavirus mouse hepatitis virus (MHV) generated during persistent infection which has allowed us to begin to address the role of the viral quasispecies in MHV pathogenesis. We analyzed the population of persisting viral RNAs using reverse-transcription polymerase chain reaction amplification (RT-PCR) of the S1 "hypervariable" region of the spike gene followed by differential colony hybridization to identify spike deletion variants (SDVs) from acute and persistently infected mice. Sequence analysis revealed that mice with the most severe chronic paralysis harbored the most complex quasispecies. Mapping of the SDVs to the predicted RNA secondary structure of the spike RNA revealed that an isolated stem loop structure is frequently deleted. Overall, these results are consistent with high frequency recombination at sites of RNA secondary structure contributing to expansion of the viral quasispecies and persisting viral pathogenesis.


title: [Detection of RNA of SARS coronavirus in hospital sewage].

text: OBJECTIVE In order to explore the existence of SARS coronavirus (Co-V) and/or its RNA in sewage of hospitals administered SARS patients. METHODS A novel electropositive filter was used to concentrate the SARS-CoV from the sewage of two hospitals administered SARS patients in Beijing, including twelve 2,500 ml sewage samples from the hospitals before disinfection, and ten 25,000 ml samples after disinfection; as well as cell culture, RT-PCR and sequencing of gene to detect and identify the viruses from sewage. RESULTS There was no live SARS-CoV detected in the sewage in this study. The nucleic acid of SARS-CoV had been found in the 12 sewage samples before disinfection from both hospitals by semi-nested PCR. After disinfection, SARS-CoV RNA could only be detected from the samples from the 309th Hospital, and the others were negative. CONCLUSION It provides evidence that there is no live SARS-Cov in the sewage from hospitals with SARS patients though SARS-CoV RNA can be detected.


title: [Digital surveillance tools for contact tracking of infected persons by SARS-CoV-2.]

text: BACKGROUND In times of pandemic, case management and tracking people with contact can be differential elements for controlling the spread. The objective of this review was to evaluate the digital tools used to track contacts of people infected with SARS-CoV-2. METHODS A systematic exploratory review was conducted in the electronic databases Pubmed, Scopus and Web of Science on May 29, 2020 through the descriptors: coronavirus, digital surveillance and contact tracing. A total of 11 studies were finally selected. RESULTS The results showed that some countries are implementing digital tools for contact tracking through mobile apps that allow user data to be shared via the device's GPS and/or Bluetooth. The terms on the privacy and confidentiality of the population data are, in some cases, questionable. CONCLUSIONS The use of digital surveillance tools to track contacts of people infected with an infectious disease, such as SARS-CoV-2, can be key to reducing the number of people infected and reducing the spread of the virus.


title: Veterinary geographic information systems applications in Nigeria: limitations, challenges and needs.

text: In developed countries, the application of geographic information systems (GIS) and other geo-information technologies in facilitating epizootiological studies of animal disease outbreaks, disease reporting, monitoring, surveillance, prediction and intervention (prevention, treatment and control) programmes, has been in vogue for decades. Although not yet in the curricula of any of Nigeria's five veterinary schools, Veterinary geo-information technologies have been promoted and applied at the Faculty of Veterinary Medicine, University of Ibadan, Nigeria, since 2001. Limitations encountered in the course of its application include poor, rudimentary and inconsistent disease reporting procedures, non-computerised (manual) disease recording techniques, raw unanalysed data, poor information networking and poor awareness of the role of geo-informatics in veterinary medicine. The major challenge is the development of sufficient and relevant veterinary databases. Major needs include the training and retraining of personnel involved in the use of GIS for veterinary medicine, the acquisition of relevant hardware and software and the funding of a Nigerian unit/centre devoted to GIS application to veterinary medicine. While Nigeria necessarily develops a national (veterinary) spatial data infrastructure, multilateral training and funding assistance is needed for a developing country like Nigeria to use developed country geo-information technologies to reduce the impact of animal diseases on animal and human populations.


title: Emerging respiratory and novel coronavirus 2012 infections and mass gatherings.

text: Mass gatherings are attended by an increasingly global audience and thus raise the concern of possible acute public health risks not normally encountered by the host population. The potential acute risks to individual and population health include communicable diseases. The communicable disease risks include emerging and re-emerging diseases in host and visiting populations. In this review, we provide an overview ofthe literature on respiratory infections at mass gatherings, then describe the impact of novel coronavirus 2012 (nCoV), an emerging respiratory disease virus, on the preparations for mass gathering. Although, nCoV emerged prior to the 2012 Hajj pilgrimage season, Muslims completed their religious duty without acquiring infections by nCoV. Clearly, the global nature of mass gatherings and their potential risks to international health make it imperative that research on such events and guidelines produced for their management are relevant to diverse contexts and are a collaborative effort between global experts.


title: [Study on the psychosocial status and related factors in three universities during severe acute respiratory syndrome epidemic in Beijing].

text: OBJECTIVE To investigate the psychosocial status and related factors among university students during severe acute respiratory syndrome (SARS) epidemic in Beijing. METHODS By means of stratified cluster sampling, symptom checklist-90 (SCL-90) and questionnaire on general information were applied among 6800 students in three universities in Beijing. RESULTS There were 6280 valid questionnaires gathered. In order to control and prevent SARS, strict management was conducted in three universities which providing various social supports. Out of the 6280 students, 460 had SCL-90 positive symptoms with a rate of 7.3%. Risk factors of SCL-90 positive symptom were found as follows: major in arts (OR = 2.00), misconception on the control and prevention of SARS (OR = 1.91), considering measures non-effective (OR = 2.25), and do not believe that SARS can be under control (OR = 3.57). Protective factors of SCL-90 positive symptom would include as: being female (OR = 0.77), being graduate students (OR = 0.38), and being not much influenced on study and daily life during the period of strict management (OR = 0.54). CONCLUSION Psychosocial status of students was influenced by their knowledge and attitude on SARS. Various social supports might keep the university students to having a healthy psychosocial status.


Electron microscopic studies of coronavirus.


title: Structural basis for 2'-5'-oligoadenylate binding and enzyme activity of a viral RNase L antagonist.

text: UNLABELLED Synthesis of 2'-5'-oligoadenylates (2-5A) by oligoadenylate synthetase (OAS) is an important innate cellular response that limits viral replication by activating the latent cellular RNase, RNase L, to degrade single-stranded RNA. Some rotaviruses and coronaviruses antagonize the OAS/RNase L pathway through the activity of an encoded 2H phosphoesterase domain that cleaves 2-5A. These viral 2H phosphoesterases are phylogenetically related to the cellular A kinase anchoring protein 7 (AKAP7) and share a core structure and an active site that contains two well-defined HΦ(S/T)Φ (where Φ is a hydrophobic residue) motifs, but their mechanism of substrate binding is unknown. Here, we report the structures of a viral 2H phosphoesterase, the C-terminal domain (CTD) of the group A rotavirus (RVA) VP3 protein, both alone and in complex with 2-5A. The domain forms a compact fold, with a concave β-sheet that contains the catalytic cleft, but it lacks two α-helical regions and two β-strands observed in AKAP7 and other 2H phosphoesterases. The cocrystal structure shows significant conformational changes in the R loop upon ligand binding. Bioinformatics and biochemical analyses reveal that conserved residues and residues required for catalytic activity and substrate binding comprise the catalytic motifs and a region on one side of the binding cleft. We demonstrate that the VP3 CTD of group B rotavirus, but not that of group G, cleaves 2-5A. These findings suggest that the VP3 CTD is a streamlined version of a 2H phosphoesterase with a ligand-binding mechanism that is shared among 2H phosphodiesterases that cleave 2-5A. IMPORTANCE The C-terminal domain (CTD) of rotavirus VP3 is a 2H phosphoesterase that cleaves 2'-5'-oligoadenylates (2-5A), potent activators of an important innate cellular antiviral pathway. 2H phosphoesterase superfamily proteins contain two conserved catalytic motifs and a proposed core structure. Here, we present structures of a viral 2H phosphoesterase, the rotavirus VP3 CTD, alone and in complex with its substrate, 2-5A. The domain lacks two α-helical regions and β-strands present in other 2H phosphoesterases. A loop of the protein undergoes significant structural changes upon substrate binding. Together with our bioinformatics and biochemical findings, the crystal structures suggest that the RVA VP3 CTD domain is a streamlined version of a cellular enzyme that shares a ligand-binding mechanism with other 2H phosphodiesterases that cleave 2-5A but differs from those of 2H phosphodiesterases that cleave other substrates. These findings may aid in the future design of antivirals targeting viral phosphodiesterases with cleavage specificity for 2-5A.


title: Counting Coronavirus Disease 2019 (COVID-19) Cases: Case Definitions, Screened Populations and Testing Techniques Matter.

text: While counting cases of disease appears straightforward, there are issues to consider when enumerating disease counts during an epidemic. For example, for Coronavirus Disease-2019 (COVID-19), how is a case defined? Hubei province in China changed its case definition twice in a fortnight-from laboratory-confirmed cases to clinically-confirmed cases without laboratory tests, and back to laboratory-confirmed cases. This caused confusion in the reported number of cases. If a confirmed case requires laboratory testing, what is the population who are laboratory-tested? Due to limited laboratory testing capacity in the early phase of an emerging epidemic, only "suspected cases" are laboratory-tested in most countries. This will result in underdiagnosis of confirmed cases and also raises the question: how is a "suspect case" defined? With the passage of time and increased capability to perform laboratory tests, more people can be screened and the number of confirmed cases will increase. What are the technical considerations of laboratory testing? This includes specimen collection (variable collection methods), samples collected (upper or lower respiratory tract biospecimens), time of collection in relation to course of disease, different laboratory test methods and kits (not all of which may be standardised or approved by authorities such as the Food and Drug Administration). Are approved laboratory facilities and trained manpower available, and how are test results interpreted and false-negatives excluded? These issues will affect the accuracy of disease counts, which in turn will have implications on how we mount an appropriate response to the outbreak.


title: Processing of the human coronavirus 229E replicase polyproteins by the virus-encoded 3C-like proteinase: identification of proteolytic products and cleavage sites common to pp1a and pp1ab.

text: Replicase gene expression by the human coronavirus 229E involves the synthesis of two large polyproteins, pp1a and pp1ab. Experimental evidence suggests that these precursor molecules are subject to extensive proteolytic processing. In this study, we show that a chymotrypsin-like enzyme, the virus-encoded 3C-like proteinase (3CLpro), cleaves within a common region of pp1a and pp1ab (amino acids 3490 to 4068) at four sites. trans-cleavage assays revealed that polypeptides of 5, 23, 12, and 16 kDa are processed from pp1a/pp1ab by proteolysis of the peptide bonds Q3546/S3547, Q3629/S3630, Q3824/N3825, and Q3933/A3934. Relative rate constants for the 3CLpro-mediated cleavages Q2965/A2966, Q3267/S3268, Q3824/N3825, and Q3933/A3934 were derived by competition experiments using synthetic peptides and recombinant 3CLpro. The results indicate that coronavirus cleavage sites differ significantly with regard to their susceptibilities to proteolysis by 3CLpro. Finally, immunoprecipitation with specific rabbit antisera was used to detect the pp1a/pp1ab processing end products in virus-infected cells, and immunofluorescence data that suggest an association of these polypeptides with intracellular membranes were obtained.


title: Persistent excretion of rotavirus by pregnant cows.

text: In a study of the epizootiology and prevalence of enteropathogens which may be involved in neonatal calf diarrhoea, 10 in-calf cows from a herd with a history of rotavirus-induced calf diarrhoea were monitored over a period of six to seven months. All the cows excreted rotavirus intermittently without showing any clinical signs, and 21.8 per cent of faecal samples contained rotavirus. Reoviruses were isolated from 87 per cent of the samples from the cows, and from all the 10 calves born to them. However, rotavirus was detected in only one calf, and diarrhoea developed only in this calf even though the calves were housed in communal pens. Campylobacter jejuni was isolated from six of the 10 dams and from five of the 10 calves, not including the calf with diarrhoea. Other potential enteropathogens such as cryptosporidium, salmonella, Clostridium difficile, coronavirus and other viruses were not found, but two cows and two calves shed enterotoxigenic Escherichia coli.


title: Quality of life in patients with chronic kidney disease: focus on end-stage renal disease treated with hemodialysis.

text: The proper measures for assessing quality of life (QOL) in patients with chronic kidney disease (CKD) remain unclear. QOL measures are subjective or objective, functional or satisfaction-based, and generic or disease-specific. Treatment of end-stage renal disease with transplantation and treatment of anemia with erythropoietin in patients with CKD have been associated with dramatic improvements of QOL. Other factors such as age, ethnic or national background, stage of CKD, modality of dialytic therapy, exercise interventions, sleep disturbances, pain, erectile dysfunction, patient satisfaction with care, depressive affect, symptom burden, and perception of intrusiveness of illness may be associated with differential perception of QOL. Recent studies showed an association between assessment of QOL and morbidity and mortality in end-stage renal disease patients, suggesting the measures do matter. Further studies are necessary in patients with early stages of CKD and in children. QOL measures should include validated psychosocial measures of depressive affect, perception of burden of illness, and social support. The challenge for the next decade will be to continue to devise interventions that meaningfully increase the QOL of patients with CKD at all stages.


title: Alphavirus M1 induces apoptosis of malignant glioma cells via downregulation and nucleolar translocation of p21WAF1/CIP1 protein.

text: Alphavirus, a genus of arthropod-borne togavirus, is well-known for its pro-apoptotic capability. However, the underlying mechanism remains to be further clarified. Here, we have identified that M1, an alphavirus isolated in 1960s, targeted C6 malignant glioma cells for apoptosis. Flow cytometry analysis showed that more cells enter S-phase post M1 infection, and subsequently undergo a classic apoptosis. To elucidate the mechanism of S-phase arrest and its relationship to apoptosis, we tested the expression of several critical cell cycle regulatory proteins and found elevated phosphorylation of cyclin-dependent kinase 2 (CDK2), decreased expression of cyclin A and proliferating cell nuclear antigen (PCNA). Notably, the protein level of p21(WAF1/CIP1) was downregulated earliest and most effectively among all tested changes of cell cycle regulators, though its mRNA level was strongly upregulated. To evaluate the role of p21(WAF1/CIP1) in S-phase accumulation and subsequent apoptosis, we confirmed that exogenous p21(WAF1/CIP1) overexpression or treatment with roscovitine (a selective chemical inhibitor of CDK2) efficiently protected against apoptosis with a reduced S-phase accumulation. Thus, it is indicated that the downregulation of p21(WAF1/CIP1) mediated C6 apoptosis via overactivation of CDK2. In addition, confocal microscopy showed that p21(WAF1/CIP1) totally translocated to nucleolus during M1-induced C6 apoptosis. Altogether, downregulation and nucleolar translocation of the p21(WAF1/CIP1) protein played an active role in M1-induced C6 apoptosis.


title: Small molecules targeting severe acute respiratory syndrome human coronavirus.

text: Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).


title: Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents.

text: Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination.


title: Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1.

text: Immunocytochemistry on serial paraffin sections was used to monitor the production dynamics of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) and viral antigens in the trigeminal ganglion (TG) and the central side of the dorsal root entry zone (DRE) of mice, following infection of the cornea with herpes simplex virus type 1. In normal TG, scattered satellite cells were TNF-alpha+ and in the DRE, TNF-alpha+ and/or low numbers of IL-6+ cells were detected. On day 3 after infection, foci of TG neurons with viral antigens were surrounded by large numbers of TNF-alpha+ and/or IL-6+ cells and low numbers of IFN-gamma+ cells. IL-2+ and/or IL-4+ cells appeared later, when viral antigens had almost cleared. In the TG, the most striking changes occurred with TNF-alpha, with respect to its source (satellite cells, Schwann cells and infiltrating cells) and the extent and long duration of its production. TNF-alpha was the predominant cytokine throughout acute and latent infection and even by day 30, numbers of satellite cells expressing this cytokine were three times higher than those in normal ganglia. Moreover, in the DRE, TNF-alpha was the only cytokine detected during virus clearance and again, its production continued, along with that of IL-6, on days 20 to 30, in both infiltrating cells and astrocytes. Thus, cytokines, particularly TNF-alpha and perhaps IL-6, from infiltrating cells and resident glial cells may have a role both in virus clearance and in normal homeostatic mechanisms in the nervous system such as repair and protection of neurons from damage.


title: Rhinovirus infection in hospitalized children in Hong Kong: a prospective study.

text: OBJECTIVES To analyze the clinical features and estimate the hospitalization disease burden of rhinovirus infection in children in Hong Kong. METHODS In this prospective study, nasopharyngeal aspirates were taken from children aged <18 years with symptoms of acute respiratory infection admitted to Queen Mary Hospital on one fixed day of the week during August 2001-July 2002 for detection of common respiratory viruses by immunofluorescence, viral culture, and for rhinovirus, human metapneumovirus, and coronaviruses by reverse transcription polymerase chain reaction. The clinical features of rhinovirus infections were analyzed and hospitalization disease burden was estimated. RESULTS Altogether 239 of the 426 nasopharyngeal aspirates (56.1%) were positive for respiratory viruses, including 151 patients with rhinovirus (35.4%). The median age was 2.34 years. Upper respiratory infection, asthma exacerbation, pneumonia, and acute bronchiolitis were diagnosed in 44.4%, 19.9%, 11.3%, and 7.9%, respectively. The most common symptoms were cough (81.5%), runny nose (76.8%), and fever (68.9%). Shortness of breath, wheezes, and crepitation were present in 25.8%, 29.1%, and 18.5%, respectively. Fifty-five of 99 patients (55.6%) had chest radiographic abnormalities, most commonly perihilar streakiness. Children with chronic diseases were more likely to have lower respiratory tract infection and these children required longer hospitalization (mean 0.6 days longer). Coinfection with other respiratory pathogens was common (33.1%). CONCLUSION Rhinovirus is frequently associated with asthmatic exacerbations and lower respiratory tract infection, especially in children with chronic diseases and is potentially an important contributor to hospitalization in children in Hong Kong.


title: [MERS-CoV: a new virus from Saudi Arabia].

text: Since about a year, a new pulmonary pathology occurred in Saudi Arabia and some cases are imported in Europa. This disease is due to a coronavirus named MERS-CoV (Middle East Respiratory Syndome Coronavirus). The main symptoms are fever, pulmonary and digestive troubles, with a risk of nosocomial transmission and a mortality of about 42%. The reservoir is probably the dromedary camel and the bat is the vector. There is no specific treatment or vaccine.


Rapid review of COVID-19.


title: Complete genome characterization and phylogenetic analysis of WU polyomavirus in Thai pediatric patients with respiratory tract infections in 2013.

text: BACKGROUND The WU polyomavirus (WUPyV) is a small DNA virus (family Polyomaviridae) that contains a circular double-stranded DNA genome, approximately 5 kb in length. WUPyV was first discovered in the respiratory tract of children with acute respiratory symptoms. OBJECTIVE This study focuses on the complete genome characterization and phylogenetic analysis of WUPyV obtained from Thai patients with respiratory diseases in 2013. MATERIAL AND METHOD DNA was extracted from nasopharyngeal (NP) suction specimens (n = 614) from patients with respiratory tract infections. WUPyV was detected by using semi-nested PCR and then characterized by whole genome sequencing. The nucleotides and deduced amino acid sequences were analyzed by multiple sequences alignment and phylogenetic tree. RESULTS Analysis revealed that 0.16% (1/614) of the sample was positive for WUPyV. Phylogenetic trees demonstrated that WUPyV(isolate CU_Chonburi 3) was closely related to previously described WUPyV. Moreover, whole genome sequences alignment of WUPyV showed several nucleotide variations within non-coding regions and amino acid changes in VP1 (position S347T); VP2 (positions L40V, G120R, Y121I, P123R, G127S, L137F, Q287R, and A327V); LTAg (positions Q357P, V369E, E377K, D378V, A381T, R382E, R383G, and D389G); and, STAg (positions R139S, K141E, R148K, and W153C). CONCLUSION Nucleotide variations within non-coding regions and critical amino acid substitutions in viral proteins may affect the rate of viral replication and viral adaptation; factors that may be linked to the susceptibility and severity of viral infection. Data obtained from this study may be useful in better understanding the genetic characterization and mutation patterns of WUPyV.


Outbreak of diarrhoea and milk drop in cows infected with bovine group B rotavirus.


title: Respiratory viral threats.

text: PURPOSE OF REVIEW To assess new information from peer-reviewed publications in 2005 regarding emerging respiratory viral threats. RECENT FINDINGS The expanding epizootic of avian A/H5N1 influenza and increasing number of human cases heighten concern regarding the threat of pandemic influenza. Studies of the 1918 pandemic virus have shown the potential for direct interspecies transmission from an avian host. In the absence of an effective vaccine, antiviral agents could provide an important response measure. Inadequate supplies and potential antiviral resistance are limiting factors. Seasonal influenza heavily affects infants and young children, who also serve to foster transmission at the community level, findings that indicate the need for broader immunization strategies in pediatric populations. Like avian influenza, the severe acute respiratory syndrome coronavirus was a zoonotic infection, perhaps derived from related coronaviruses in bats. Molecular diagnostic techniques have led to the recent identification of several new coronaviruses and a respiratory parvovirus. It has also helped to define the impact of previously described ones such as human metapneumovirus and rhinoviruses, which account for the majority of asthma exacerbations and frequent lower respiratory tract illnesses. SUMMARY Progress has been made in development of possible specific interventions for influenza and possibly severe acute respiratory syndrome coronavirus, but effective antivirals and vaccines for most other respiratory viruses are currently lacking.


title: Typing infectious bronchitis virus strains using reverse transcription-polymerase chain reaction and restriction fragment length polymorphism analysis to compare the 3' 7.5 kb of their genomes.

text: Typing infectious bronchitis virus (IBV) strains is useful for implementation of control measures and for understanding the epidemiology and evolution of IBV. The aim of the work reported here was to develop a rapid and sensitive method for typing isolates of IBV, if possible directly from tissues of infected birds. A procedure was developed for differentiation of IBV strains by restriction endonuclease fragment length polymorphism (RFLP) analysis of a 7.5 kb DNA fragment amplified from their genome by reverse transcription-polymerase chain reaction (RT-PCR). This fragment encompassed all of the genes encoding the structural proteins of the virus. Viral RNA was extracted either directly from tissues of diseased birds or from virus propagated in embryonated eggs, and was subjected to RT-PCR. Three different restriction endonucleases, AluI, Sau3AI and MnlI, were used to digest the 7.5 kb PCR product from different IBV strains and the resultant RFLP patterns were compared. Patterns obtained with all three enzymes grouped IBV strains belonging to the same serotype in the same cluster. These results show that the RT-PCR-RFLP system described here can be used as a quick and inexpensive tool for differentiating IBV strains.


title: Idiopathic CD4 lymphocytopenia.

text: PURPOSE OF REVIEW A severe decrease of CD4 T cells predisposes humans to opportunistic infections. In adults, HIV is certainly the most common cause of CD4 lymphocytopenia, but other causes, such as infections, autoimmune diseases, immunosuppressive therapy, lymphoma and idiopathic forms need to be considered. This review summarizes the current knowledge of the poorly understood syndrome of idiopathic CD4 lymphocytopenia. RECENT FINDINGS Little research has tried to systematically dissect this probably heterogeneic syndrome after its initial description in 1992. Numerous cases presenting with opportunistic infections have been reported. Disturbed differentiation of stem cell precursors may contribute to CD4 lymphocytopenia. Because infections and lymphoma may also cause CD4 lymphocytopenia, the distinction between cause and effect may evolve only during follow-up. SUMMARY The manifestation of opportunistic infections calls for the evaluation of the immune system for CD4 lymphocytopenia. The differential diagnosis of this condition in adults comprises primarily HIV infection and less often other diseases or drugs. Idiopathic CD4 lymphocytopenia is very rare. The clinical significance of low CD4 cell counts in HIV negative patients still awaits its systematic analysis. Prophylaxis of opportunistic infections is oriented at the recommendations of HIV-infected individuals and causal treatment remains experimental.


title: Localization of astrovirus in experimentally infected turkeys as determined by in situ hybridization.

text: Twenty-one 3-day-old turkey poults from British United Turkeys of America were orally inoculated with a recently characterized astrovirus, TAstV-2, isolated from turkeys with poult enteritis and mortality syndrome. At 1, 2, 3, 4, 5, 7, and 9 days postinfection (dpi), three inoculated birds were euthanatized, and tissues (intestines, spleen, bursa, and thymus) were collected immediately into 10% neutral buffered formalin. Inoculated birds were diarrheic by 3 dpi, and frothy feces persisted throughout the experimental period. Histologically, there was only slight evidence of enteric damage, which was characterized by mild epithelial necrosis, lamina propria infiltrates, minimal villus atrophy, and mild crypt hyperplasia. In situ hybridization, using a negative sense digoxigenin-labeled riboprobe to the capsid gene of TAstV-2, revealed viral RNA in intestinal epithelial cells at the basal margins of the villi, in distal small intestine, and in cecum at 2 dpi, with subsequent extension to epithelium of the large intestine and proximal small intestine (3-5 dpi). Minimal virus remained by 9 dpi.


title: Inhalational induction with "vasoparalytic" sevoflurane: are we "hyperoxygenating" while anesthetizing developing brains? A case series discussion.

text: BACKGROUND The concerns for hyperoxia-related brain tissue injury are well known to the medical community. The cerebro-vasodilatory properties of sevoflurane may create relative cerebral tissue "hyperoxia" during inhalational induction as compared to a propofol-based intravenous induction of anesthesia. STUDY OBJECTIVES The objective for this case series discussion was to identify any differences in cerebral tissue oxygenation secondary to induction of anesthesia with sevoflurane versus propofol. METHODS/STUDY PROCEDURES: After institutional review board approval, the computer data of tissue cerebral oximetry of pediatric patients (1-18 years age group) undergoing non-cardiac surgeries was comparatively analyzed for changes over time between the groups of children who received sevoflurane induction versus propofol induction of anesthesia. "Hyperoxia" ("hyperoxygenation") was defined as significant percent changes from the baseline values as recorded in tissue cerebral oximetry. RESULTS In this case series, seven patients underwent inhalational (INH) induction with high concentrations (8%) sevoflurane with nitrous oxide in 33% oxygen and four patients underwent intravenous (i.v.) induction with 2 mg/kg propofol and nitrous oxide in 33% oxygen. As compared to propofol, significant cerebral tissue "hyperoxia" occurred with sevoflurane induction (p = 0.003). This did not resolve over time. CONCLUSION As compared to intravenous induction with propofol, inhalational induction with "vasoparalytic" sevoflurane "hyperoxygenates" developing brains. This observation requires validation in larger trials to conclude appropriate effect on our practice of pediatric anesthesia and pediatric patient safety under anesthesia.


title: Efficacy and safety of psychostimulants for amphetamine and methamphetamine use disorders: a systematic review and meta-analysis.

text: BACKGROUND Amphetamine and methamphetamine use disorders are associated with severe health and social consequences. No pharmacological therapy has been approved for the treatment of these disorders. Psychostimulants can act as maintenance-like therapies for managing substance use among these patients. The aim of this study is to evaluate the literature examining the efficacy and safety of psychostimulant agents for increasing abstinence and treatment retention among patients with amphetamine and methamphetamine use disorders. METHODS We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central, and CINAHL from inception to August 2016. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. We conducted meta-analyses to provide a pooled summary estimate for included trials and report the review according to PRISMA guidelines. RESULTS We identified and selected 17 studies with 1387 participants. Outcome reporting across trials was inconsistent, and the overall quality of evidence was very low due to high risk of bias and indirectness. A meta-analysis of five trials (642 participants) found no effect of psychostimulants for end-of-study abstinence (odds ratio = 0.97, 95% confidence interval 0.65 to 1.45). Additionally, the pooled estimate from 14 studies (1184 participants) showed no effect of psychostimulants for treatment retention (odds ratio = 1.20, 95% confidence interval = 0.91 to 1.58). The incidence of serious adverse events did not differ between intervention and placebo groups based on qualitative reports from trials. CONCLUSIONS Quantitative analyses showed no effect of psychostimulants for sustained abstinence or treatment retention. We also identified the need for more rigorous studies in this research area with clinician and patient important outcomes.


title: 'Primer alignment-and-extension': a novel mechanism of viral RNA recombination responsible for the rescue of inactivated poliovirus cDNA clones.

text: In the course of experiments designed to assess the potential role of alternative open reading frames (ORF) present in the 5'-terminal untranslated region (5'-UTR) of poliovirus type 1 (Mahoney strain) genomic RNA, we came across a double mutation that completely abrogated the infectivity of full-length cDNA clones. The infectivity was rescued in trans by cotransfecting COS-1 cells with short RNA transcripts of the wild-type 5'-UTR of poliovirus type 2 Lansing, provided a free 3'-OH was available. Direct sequencing of the viral RNA revealed that the infectious viruses recovered were recombinants Lansing/Mahoney, with variable points of 'crossing-over'. A novel mechanism of RNA-RNA recombination, which we propose to call 'primer alignment-and-extension', is described that would explain the high rate of recombination of RNA viruses observed in natural conditions.


title: The safety and usefulness of the single incision, transabdominal pre-peritoneal (TAPP) laparoscopic technique for inguinal hernia.

text: BACKGROUND The safety and usefulness of the SILS-TAPP (transabdominal pre-peritoneal) procedure remain unclear. The aim of this study was to clarify the safety and usefulness of the SILS-TAPP procedure compared with standard laparoscopic TAPP and TEPP (totally extra-peritoneal pre-peritoneal) procedures. PATIENTS AND METHODS 85 patients underwent laparoscopic inguinal hernia repairs (TEPP, 30 patients; TAPP, 20 patients; SILS-TAPP, 35 patients) from 2007 to 2011. The operative outcomes of the three groups were compared. RESULTS There was no difference in the patients' characteristics among the three groups. The TEPP Group had a longer operation time. One patient in the SILS-TAPP group had an intraoperative complication. One patient in the TAPP group had a postoperative complication, and one patient had ileus and one had an umbilical hernia in the SILS-TAPP group. The postoperative hospital stay was not significantly different among the three groups. There were no recurrences in the TEPP group, 1 case of recurrence (5.0%) in the TAPP group, and 1 case (2.9%) in the SILS-TAPP group. CONCLUSIONS The present findings show that the SILS-TAPP repair is safe and feasible for the repair of adult inguinal hernia.


title: [COVID-19 in the intensive care unit. Analysis of the experience during the first month of pandemic].

text: This is an analysis of clinical characteristics, images findings, laboratory variables and respiratory mechanics in patients with coronavirus disease 2019 (COVID-19) during the first month of the pandemic outbreak in Buenos Aires. In this descriptive case study of a single-centre, we included all confirmed cases of COVID-19 hospitalized in intensive care unit (ICU). All cases were confirmed by reverse transcription polymerase chain reaction. A total of 7 patients with confirmed COVID-19 were referred to out ICU. The median age was 71 years (interquartile range 52-75), including 4 men and 3 women. Patients most common clinical manifestations were fever (7), cough (5), asthenia (4) and shortness of breath (3). Among the radiological findings, five of them showed interstitial opacities and one patient had bilateral pulmonary consolidation. Five required invasive mechanical ventilation and multiple prone sessions. None died during hospitalization, although three still remain in the ICU. According to imaging examination, 71.4% showed interstitial opacities and one patient bilateral consolidation. Five patients required invasive mechanical ventilation and multiple prone sessions. None of them died during hospitalization, although three still remain in the ICU.


title: Sensitivity of Tru-cut and fine needle aspiration biopsies of liver and kidney for diagnosis of feline infectious peritonitis.

text: BACKGROUND The detection of typical lesions and feline coronavirus (FCoV) antigen in tissues is the only conclusive method for making a diagnosis of feline infectious peritonitis (FIP). A positive result using Tru-cut biopsy (TCB) and fine-needle aspiration biopsy (FNAB) has high diagnostic specificity, but information about the capacity of these techniques to correctly identify cats with FIP lesions is not available. OBJECTIVES The diagnostic sensitivity of TCB and FNAB for detecting liver and kidney histologic lesions caused by FIP was evaluated. METHODS TCB and FNAB specimens collected mainly at necropsy from 25 cats with FIP were analyzed. Diagnostic sensitivity was calculated on the basis of the number of false-negative and true-positive specimens, compared with the number of organs bearing histologic lesions of FIP. RESULTS Diagnostic sensitivity was higher for hepatic TCB (64%) and FNAB (82%) than for renal (39% and 42%, respectively) procedures. A high percentage of renal cytologic and TCB specimens were inadequate. Combined analysis of TCB and FNAB specimens collected from the same organ increased the diagnostic sensitivity for liver (86%) and kidney (48%). The sensitivity of immunohistochemical/cytochemical analysis was low (11-38% depending on the technique), probably due to variable distribution of feline coronavirus in the lesions. CONCLUSION Biopsy of liver and kidney can correctly identify FIP lesions. However, false-negative results or inadequate samples occur with moderate frequency, especially for immunochemical analysis. Diagnostic sensitivity may be increased when both TCB and FNAB specimens from the same organ are examined.


title: Inhibition, escape, and attenuated growth of severe acute respiratory syndrome coronavirus treated with antisense morpholino oligomers.

text: The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) is a potent pathogen of humans and is capable of rapid global spread. Peptide-conjugated antisense morpholino oligomers (P-PMO) were designed to bind by base pairing to specific sequences in the SARS-CoV (Tor2 strain) genome. The P-PMO were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral RNA motifs and secondary structures. Several virus-targeted P-PMO and a random-sequence control P-PMO showed low inhibitory activity against SARS coronavirus. Certain other virus-targeted P-PMO reduced virus-induced cytopathology and cell-to-cell spread as a consequence of decreasing viral amplification. Active P-PMO were effective when administered at any time prior to peak viral synthesis and exerted sustained antiviral effects while present in culture medium. P-PMO showed low nonspecific inhibitory activity against translation of nontargeted RNA or growth of the arenavirus lymphocytic choriomeningitis virus. Two P-PMO targeting the viral transcription-regulatory sequence (TRS) region in the 5' untranslated region were the most effective inhibitors tested. After several viral passages in the presence of a TRS-targeted P-PMO, partially drug-resistant SARS-CoV mutants arose which contained three contiguous base point mutations at the binding site of a TRS-targeted P-PMO. Those partially resistant viruses grew more slowly and formed smaller plaques than wild-type SARS-CoV. These results suggest PMO compounds have powerful therapeutic and investigative potential toward coronavirus infection.


title: Host cell cathepsins potentiate Moloney murine leukemia virus infection.

text: The roles of cellular proteases in Moloney murine leukemia virus (MLV) infection were investigated using MLV particles pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein as a control for effects on core MLV particles versus effects specific to Moloney MLV envelope protein (Env). The broad-spectrum inhibitors cathepsin inhibitor III and E-64d gave comparable dose-dependent inhibition of Moloney MLV Env and VSV G pseudotypes, suggesting that the decrease did not involve the envelope protein. Whereas, CA-074 Me gave a biphasic response that differentiated between Moloney MLV Env and VSV G at low concentrations, at which the drug is highly selective for cathepsin B, but was similar for both glycoproteins at higher concentrations, at which CA-074 Me inhibits other cathepsins. Moloney MLV infection was lower on cathepsin B knockout fibroblasts than wild-type cells, whereas VSV G infection was not reduced on the B-/- cells. Taken together, these results support the notion that cathepsin B acts at an envelope-dependent step while another cathepsin acts at an envelope-independent step, such as uncoating or viral-DNA synthesis. Virus binding was not affected by CA-074 Me, whereas syncytium induction was inhibited in a dose-dependent manner, consistent with cathepsin B involvement in membrane fusion. Western blot analysis revealed specific cathepsin B cleavage of SU in vitro, while TM and CA remained intact. Infection could be enhanced by preincubation of Moloney MLV with cathepsin B, consistent with SU cleavage potentiating infection. These data suggested that during infection of NIH 3T3 cells, endocytosis brings Moloney MLV to early lysosomes, where the virus encounters cellular proteases, including cathepsin B, that cleave SU.


title: Viral gastroenteritis and diversity of Rotavirus strains in Colombian children: a systematic review.

text: BACKGROUND To determine the epidemiological profile of viruses associated with acute gastroenteritis in children younger than 5 years of age and the distribution of rotavirus genotypes circulating in Colombia. METHODOLOGY We conducted a review of 23 studies published in Spanish and English, plus an analysis of the detection rates of rotavirus as well as other viruses associated with acute gastroenteritis in young children from 1984 to 2006 in the three Colombian regions. This review also included the only two studies conducted to date (published between 2004 and 2006) reporting G-P rotavirus strains using RT-PCR. RESULTS The median detection rate of group A Rotavirus was 35.2% (range, 2.2%-57.4%) and those for Calicivirus, Astrovirus and Adenovirus 40/41 were 10.4%, 2.7% and 1.35%, respectively. The more commonly reported rotavirus GP combination, G3P [8] (32.7%) was more frequently documented than both G1P [8] (24.7%) and G2P [4] (22.9%). The G9 genotype, which is considered emergent, was also reported. CONCLUSIONS Group A Rotavirus was frequently associated with diarrhoea in children from the three regions. There was regional variation in rotavirus detection rates. Continual surveillance is needed to inform diarrhoea prevention programs as well as to provide information about the occurrence of native rotavirus strains.


title: Heterogeneous shedding of Escherichia coli O157 in cattle and its implications for control.

text: Identification of the relative importance of within- and between-host variability in infectiousness and the impact of these heterogeneities on the transmission dynamics of infectious agents can enable efficient targeting of control measures. Cattle, a major reservoir host for the zoonotic pathogen Escherichia coli O157, are known to exhibit a high degree of heterogeneity in bacterial shedding densities. By relating bacterial count to infectiousness and fitting dynamic epidemiological models to prevalence data from a cross-sectional survey of cattle farms in Scotland, we identify a robust pattern: approximately 80% of the transmission arises from the 20% most infectious individuals. We examine potential control options under a range of assumptions about within- and between-host variability in infection dynamics. Our results show that the within-herd basic reproduction ratio, R(0), could be reduced to <1 with targeted measures aimed at preventing infection in the 5% of individuals with the highest overall infectiousness. Alternatively, interventions such as vaccination or the use of probiotics that aim to reduce bacterial carriage could produce dramatic reductions in R(0) by preventing carriage at concentrations corresponding to the top few percent of the observed range of counts. We conclude that a greater understanding of the cause of the heterogeneity in bacterial carriage could lead to highly efficient control measures to reduce the prevalence of E. coli O157.


Immunization in Canada 2007.


docid: baxgimmy

title: Successful sequencing of the first SARS-CoV-2 genomes from Croatian patients.


title: [Analysis of Symptoms Relieved in Addition to Pain after Administration of Oxycodone or Morphine to Patients with Advanced Cancer Living at Home].

text: Cancer pain was observed in 131 of 160 patients with advanced cancer living at home. Oxycodone or morphine was administered to patients suffering from cancer pain or fentanyl transdermal patch was switched to morphine. Subsequently, 70 patients were found to have alleviation of symptoms such as nausea/vomiting, dyspnea, abdominal fullness, general fatigue, cough, and urinary urgency in addition to pain. Pain was defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage by the International Association for the Study of Pain. This definition of pain is cited in a lot of books. However, the author was unable to intervene with detailed reports of unpleasant sensations associated with tissue damage. Therefore, here the author reports about an unpleasant sensation caused by tissue damage of cancer that was alleviated by oxycodone or morphine.


title: Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination.

text: Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed. An average of 30 mug of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro. Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism.


title: Complications and Failure of Endovenous Laser Ablation and Radiofrequency Ablation Procedures in Patients With Lower Extremity Varicose Veins in a 5-Year Follow-Up.

text: INTRODUCTION Thermal ablation techniques have gradually replaced Babcock procedure in varicose vein treatment. AIM A comparative quantitative-qualitative analysis of complications and failure of endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in a 5-year follow-up. MATERIALS AND METHODS One hundred ten adult participants with varicose veins clinical grade C2 to C6, treated for isolated great saphenous vein (GSV) or small saphenous vein (SSV) insufficiency in a single lower extremity in 2009 to 2010, were enrolled and subdivided into EVLA (n = 56) and RFA (n = 54) groups. Both groups were compared for demography, disease stage, affected veins, perioperative, and postoperative complications as well as treatment efficacy. RESULTS The perioperative and postoperative complications were statistically insignificant. Treatment efficacy, expressed as the number of participants with recurrent varicosity and recanalization, was comparable in both groups. The clinically significant recanalization rate was 3.6% and 5.6% in EVLA and RFA groups, respectively. CONCLUSION Endovenous laser ablation and RFA for the management of lower extremity varicose vein offer comparable efficacy and safety in a 5-year follow-up.