title: trans regulation of cap-independent translation by a viral subgenomic RNA.

text: Many positive-strand RNA viruses generate 3'-coterminal subgenomic mRNAs to allow translation of 5'-distal open reading frames. It is unclear how viral genomic and subgenomic mRNAs compete with each other for the cellular translation machinery. Translation of the uncapped Barley yellow dwarf virus genomic RNA (gRNA) and subgenomic RNA1 (sgRNA1) is driven by the powerful cap-independent translation element (BTE) in their 3' untranslated regions (UTRs). The BTE forms a kissing stem-loop interaction with the 5' UTR to mediate translation initiation at the 5' end. Here, using reporter mRNAs that mimic gRNA and sgRNA1, we show that the abundant sgRNA2 inhibits translation of gRNA, but not sgRNA1, in vitro and in vivo. This trans inhibition requires the functional BTE in the 5' UTR of sgRNA2, but no translation of sgRNA2 itself is detectable. The efficiency of translation of the viral mRNAs in the presence of sgRNA2 is determined by proximity to the mRNA 5' end of the stem-loop that kisses the 3' BTE. Thus, the gRNA and sgRNA1 have "tuned" their expression efficiencies via the site in the 5' UTR to which the 3' BTE base pairs. We conclude that sgRNA2 is a riboregulator that switches off translation of replication genes from gRNA while permitting translation of structural genes from sgRNA1. These results reveal (i) a new level of control of subgenomic-RNA gene expression, (ii) a new role for a viral subgenomic RNA, and (iii) a new mechanism for RNA-mediated regulation of translation.


Personal protective equipment for preventing respiratory infections: what have we really learned?


title: Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Thus, vaccination against SARS-CoV may represent an effective approach towards controlling SARS. The nucleocapsid (N) protein is thought to play a role in induction of cell-mediated immunity to SARS-CoV and thus it is important to characterize this protein. In the present study, an E1/partially E3-deleted, replication-defective human adenovirus 5 (Ad5) vector (Ad5-N-V) expressing the SARS-CoV N protein was constructed. The N protein, expressed in vitro by Ad5-N-V, was of the expected molecular mass of 50 kDa and was phosphorylated. Vaccination of C57BL/6 mice with Ad5-N-V generated potent SARS-CoV-specific humoral and T cell-mediated immune responses. These results show that Ad5-N-V may potentially be used as a SARS-CoV vaccine.


Identification and control are the priority.


title: Fusion formation by the uncleaved spike protein of murine coronavirus JHMV variant cl-2.

text: The fusogenic properties of the uncleaved spike (S) protein of murine coronavirus JHMV variant cl-2 were studied by expressing the S protein with a deleted putative cleavage site. The amino acid sequence of the putative cleavage site, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala-Leu-Glu by in vitro mutagenesis of the cl-2 S protein cDNA. Recombinant vaccinia viruses containing the cl-2 S cDNA [RVV t(+)] or the mutated cDNA [RVV t(-)] were constructed and monitored for fusion formation and cleavage of the expressed S proteins. When cultured DBT cells were infected with RVV t(+) at a multiplicity of infection of 0.5, fusion formation was first observed at 10 to 12 h postinoculation and spread throughout the whole culture by 20 to 24 h postinoculation. In cells infected with RVV t(-) under the same conditions, fusion formation appeared by 12 to 14 h. This result represented a 2- to 4-h delay in the onset of fusion, compared with its appearance in cells expressing the wild-type S protein. By 25 to 30 h, most of the cells infected by RVV t(-) had fused. By immunoprecipitation and Western blotting (immunoblotting), the 170-kDa S protein was detected in DBT cells expressing the wild-type S protein and the mutated S protein. However, interestingly, the cleavage products of the S protein, S1 and S2, were not detected in RVV t(-)-infected cells, producing the mutated S protein, even though fusion was clearly visible. Both products were, of course, detected in RVV t(+)-infected DBT cells, producing the wild-type S protein. The same results concerning the fusion formation and cleavage properties of the S proteins were reproduced by the transiently expressed S proteins. These results suggest that the cleavage event in the S protein of murine coronavirus JHMV is not a prerequisite for fusion formation but that it does facilitate fusion formation.


Oral antihistamine/decongestant/analgesic combinations for the common cold.


title: Unusual heterogeneity of leader-mRNA fusion in a murine coronavirus: implications for the mechanism of RNA transcription and recombination.

text: Coronavirus mRNA transcription was thought to be regulated by the interaction between the leader RNA and the intergenic sequence (IS), probably involving direct RNA-RNA interactions between complementary sequences. In this study, we found that a particular strain of mouse hepatitis virus, JHM2c, which has a deletion of a 9-nucleotide (nt) sequence (UUUAUAAAC) immediately downstream of the leader RNA, transcribed subgenomic mRNA species containing a whole array of heterogeneous leader fusion sites. Using a transfected defective interfering RNA which contains an IS and a reporter (chloramphenicol acetyltransferase) gene and JHM2c as a helper virus, we demonstrated that subgenomic mRNAs transcribed from the defective interfering RNAs were extremely heterogeneous. The leader-mRNA fusion sites in this virus can be grouped into five types. In type I, the leader is fused with the consensus IS of the template RNA at a site within the UCUAA repeats, consistent with the classical model of discontinuous transcription. In type II, the leader is fused with the consensus IS as in type I, but the leader of mRNA contains some nucleotide substitutions within the UCUAA repeats. In type III, the leader is fused with mRNAs at a site either upstream or downstream of the consensus IS. The sequences around the fusion sites bear little or no homology to the leader. As a result, mRNAs contain sequences complementary to the template sequences upstream of the IS or have sequence deletions downstream of the IS. In type IV, the leader is fused to the IS at the 9-nt sequence immediately downstream of the UCUAA repeats. In type V, the leader-mRNA fusion site contains a duplication of a portion of the leader sequence or an insertion of nontemplated sequences which are not present in either leader or template RNA. These patterns of leader-mRNA fusion resemble the aberrant homologous recombination frequently seen in other RNA viruses. The degree of heterogeneity of leader fusion sites is dependent on the sequences of both the leader RNA and IS. These results suggest that leader-mRNA fusion in coronavirus transcription does not require direct RNA-RNA interaction between complementary sequences. A modified model of RNA transcription and recombination based on protein-RNA and protein-protein interactions is proposed. This study also provides a paradigm for aberrant homologous recombination.


title: A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.

text: Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves were administered sucrose and diuretic agents for 48 h to induce diarrhea and severe dehydration. Clinical changes after 48 h were severe watery diarrhea, severe depression, and marked dehydration (mean, 14% BW loss). Cardiac output, stroke volume, mean central venous pressure, plasma volume, thiocyanate space, blood pH and bicarbonate concentration, base excess, serum chloride concentration, and fetlock temperature were decreased. Plasma lactate concentration, hematocrit, and serum potassium, creatinine, phosphorus, total protein and albumin concentrations were increased. This non-infectious calf diarrhea protocol has a 100% response rate, while providing a consistent and predictable hypovolemic state with diarrhea that reflects most of the clinicopathologic changes observed in osmotic/maldigestive diarrhea caused by infection with rotavirus, coronavirus or cryptosporidia. Limitations of the protocol, when compared to infectious diarrhea models, include failure to induce a severe metabolic acidosis, absence of hyponatremia, renal instead of enteric loss of chloride, renal as well as enteric loss of free water, absence of profound clinical depression and suspected differences in the morphologic and functional effect on intestinal epithelium. Despite these differences, the sucrose/diuretic protocol should be useful in the initial screening of new treatment modalities for calf diarrhea. To confirm their efficacy, the most effective treatment methods should then be examined in calves with naturally-acquired diarrhea.


title: Coronaviruses in bent-winged bats (Miniopterus spp.).

text: A novel group 1 coronavirus was previously identified in bent-winged bats (Miniopterus spp.). Here, results are described from our ongoing surveillance of these bats for coronaviruses. These findings show that group 1 coronaviruses are endemic in these bat populations in Hong Kong. Genetic analysis of these viruses indicates that there are at least four different, but closely related, group 1 coronaviruses (bat-CoV 1A, 1B, HKU7 and HKU8) circulating in bent-winged bats. Phylogenetic analysis revealed that these group 1 bat coronaviruses have descended from a common ancestor and that these viruses have been established in these bats for a long period of time. These data provide a better understanding of the emergence and evolution of coronaviruses. Bat-CoV 1A and 1B were detected in apparently healthy Miniopterus magnater and Miniopterus pusillus, respectively, on repeated sampling occasions at a single habitat, suggesting that these viruses have established a persistent infection in these populations.


title: Right upper lobe collapse secondary to an anomalous bronchus after endotracheal intubation for routine surgery.

text: Perioperative hypoxaemia is a common but serious problem with well recognised causes. However, an anomalous bronchus causing lobar collapse as a cause is seldom mentioned. A healthy young male patient was anaesthetised for a knee operation. He required re-intubation immediately postoperatively for hypoxia. He was found to have right upper lobe collapse. Fibreoptic examination of the trachea demonstrated an anomalous bronchus as the cause. Intra-operatively, the endotracheal tube had been inserted too deeply and the bronchial orifice had been obstructed by the tip. It took several hours for the lung to re-expand. Greater awareness of this potential complication is needed.


title: Review of retention strategies in longitudinal studies and application to follow-up of ICU survivors.

text: OBJECTIVE To review the literature on retention strategies in follow-up studies and their relevance to critical care and to comment on the Toronto experience with the acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome (SARS) follow-up studies. DESIGN AND SETTING Literature review and two cohort studies in a tertiary care hospital in Toronto, Canada. PATIENTS AND PARTICIPANTS ARDS and SARS patients. MEASUREMENTS AND RESULTS Review articles from the social sciences and medicine are summarized and our own experience with two longitudinal studies is drawn upon to elucidate strategies that can be successfully used to attenuate participant drop-out from longitudinal studies. Three key areas for retention of subjects are identified from the literature: (a) respect for patients: respect for their ideas and their time commitment to the research project; (b) tracking: collect information on many patient contacts at the initiation of the study and outline tracking procedures for subjects lost to follow-up; and (c) study personnel: interpersonal skills must be reinforced, flexible working hours mandated, and support offered. Our 5-year ARDS and 1-year SARS study retention rates were 86% and 91%, respectively, using these methods. CONCLUSIONS Strategies to reduce patient attrition are time consuming but necessary to preserve internal and external validity. When the follow-up system is working effectively, researchers can acquire the necessary data to advance knowledge in their field and patients are satisfied that they have an important role to play in the research project.


docid: alnartch

title: Measurement of intra-abdominal pressure in large incisional hernia repair to prevent abdominal compartmental syndrome.

text: INTRODUCTION The repair of large incisional hernias may occasionally lead to a substantial increase in intra-abdominal pressure (IAP), and rarely to abdominal compartmental syndrome (ACS) with subsequent respiratory, vascular, and visceral complications. Measurement of the IAP has recently become a common practice in monitoring critical patients, even though such measurements were obtained in the early 1900s. PATIENTS AND METHODS A prospective study involving 54 patients undergoing elective abdominal wall gap repair (mean length, 17.4 cm) with a tension-free technique after incisional hernia was conducted. The purpose of the study was to determine whether or not urinary pressure for indirect IAP measurement is a reliable method for the early identification of patients with a higher risk of developing ACS. IAP measurements were performed using a Foley catheter connected to a HOLTECH® medical manometer. IAP values were determined preoperatively, after anesthetic induction, upon patient awakening, upon patient arrival in the ward after surgery, and 24 h after surgery before removing the catheter. All patients were treated by the same surgical team using a prosthetic composite mesh (PARIETEX®). RESULTS Incisional hernia repair caused an increase in the mean IAP score of 2.68 mmHg in 47 of 54 patients (87.04%); the IAP was decreased in two patients (3.7%) and remained equal in five patients before and 24 h after surgery (9.26%). FEV-1, measured 24 h after surgery, increased in 50 patients (92.6%), remained stable in two patients (3.7%), and decreased in two patients (3.7%). The mean increase in FEV-1 was 0.0676 L (maximum increase = 0.42 L and minimum increase = 0.01 L) in any patient who developed ACS. CONCLUSIONS Measurement of urinary bladder pressure has been shown to be easy to perform and free of complications. Measurement of urinary bladder pressure can also be a useful tool to identify patients with a higher risk of developing ACS.


title: Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state.

text: The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.


title: Balloon-assisted coiling of the cavernous sinus to treat direct carotid cavernous fistula. A single center experience of 13 consecutive patients.

text: This study evaluated clinical and neuroradiological results in 13 consecutive patients with spontaneous and traumatic direct carotid cavernous fistulas treated at our center between January 2006 and September 2012. All patients were treated by coiling of the cavernous sinus. Coiling was always performed while a semi-compliant non-detachable balloon was temporarily inflated in the internal carotid artery. This technique (balloon-assisted coiling) permitted a clear visualization of the fistula, facilitated coil positioning and protected the patency of the artery. All patients' clinical data and radiological examinations were reviewed; nine patients underwent radiological and clinical follow-up, with a mean duration of 3.8 years (range: six months-six years). Overall results at discharge showed a complete occlusion of the fistula in seven patients (7/13, 54%) and a resolution of symptoms in eight patients (8/12, 67%). Radiological follow-up showed complete occlusion of the fistula in all patients (9/9, 100%) and clinical follow-up showed a resolution of symptoms in eight patients (8/9, 89%) and persistent symptoms in one (1/9, 11%). No procedure-related complications occurred. Balloon-assisted coiling of the cavernous sinus for the treatment of direct carotid cavernous fistulas proved an effective and safe technique, both in angiographic and clinical terms, and may be considered a technical improvement.


docid: ikprtjes

title: Fear, Preparedness and Covid-19.


title: Severe acute respiratory syndrome: another challenge for critical care nurses.

text: Severe acute respiratory syndrome (SARS) is a viral disease that may be contracted by exposure to a newly recognized form of the coronavirus. It often manifests through a set of common respiratory symptoms that include fever and nonproductive cough. To date, SARS has no vaccine or definitive treatment. Approximately 20% of SARS patients develop respiratory failure, which requires mechanical ventilation and close cardiopulmonary monitoring. Intensive care unit (ICU) nurses and other healthcare workers who care for SARS patients are at risk of contracting the disease. Thus, it is important that ICU nurses be familiar with the disease and its implications for critical care. This article provides critical care nurses with an update on the first SARS outbreak, its origin, case definition, clinical manifestations, diagnosis, relevant infection control practices, management, and recommendations for the role of ICU nurses in dealing with future outbreaks.


title: Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecal Escherichia coli.

text: Fifty-two newborn Holstein calves with serum IgG concentrations less than 0.73 g.dL(-1) were randomly assigned to one of four treatments: no added live yeast (control), 0.5 g of live yeast added to the grain for 84 d (SC; Saccharomyces cerevisiae), 0.5 g of live yeast added to the milk for 42 d (SB; S. cerevisiae, spp. boulardii), and 0.5 g of live yeast added to the grain for 84 d and to the milk for 42 d (SCSB). Calves were offered 440 g of milk replacer DM for the first 42 d and grain for ad libitum intake throughout the study. Plasma was analyzed weekly for concentrations of glucose and beta-hydroxybutyrate. Escherichia coli isolated from fecal samples collected every 2 weeks were used for determination of antibiotic resistance patterns. Calves receiving SC consumed more grain DM, had increased weight gain prior to weaning, and increased plasma glucose concentrations compared to controls. Days with diarrhea were reduced by feeding live yeast to calves. Antibiotic resistance in fecal E. coli was associated with the age of calves with highest levels of resistance observed in the 3 d calves. While calves receiving SCSB had higher levels of antibiotic resistance than controls, this effect was not associated with any of the other treatments. Improvements in performance of calves with failure of passive transfer were observed when live yeast was added only to the grain.


title: The use of the bispectral index in the detection of pain in mechanically ventilated adults in the intensive care unit: a review of the literature.

text: BACKGROUND Pain assessment is an immense challenge for clinicians, especially in the context of the intensive care unit, where the patient is often unable to communicate verbally. Several methods of pain assessment have been proposed to assess pain in this environment. These include both behavioural observation scales and evaluation of physiological measurements such as heart rate and blood pressure. Although numerous validation studies pertaining to behavioural observation scales have been published, several limitations associated with using these measures for pain assessment remain. Over the past few years, researchers have been interested in the use of the bispectral index monitoring system as a proxy for the evaluation of encephalography readings to assess the level of anesthesia and, potentially, analgesia. OBJECTIVES To synthesize the main studies exploring the use of the bispectral index monitoring system for pain assessment, to guide future research in adults under sedation in the intensive care unit. METHOD The EMBASE, Medline, CINAHL and PsycINFO databases were searched for studies published between 1996 and 2013 that evaluated the use of the bispectral index in assessing pain. RESULTS Most studies conclude that nociceptive stimulation causes a significant increase in the bispectral index and revealed the importance of controlling certain confounding variables such as the level of sedation. DISCUSSION Further studies are needed to clearly demonstrate the relationship between nociceptive stimuli and the bispectral index, as well as the specificity of the bispectral index in detecting pain.


title: Murine coronavirus-induced subacute fatal peritonitis in C57BL/6 mice deficient in gamma interferon.

text: Gamma interferon-deficient (IFN-gamma-/-) mice with a C57BL/6 background were infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In contrast to IFN-gamma-+/- and IFN-gamma+/+ mice, JHMV persisted in IFN-gamma-/- mice and induced death during the subacute phase of the infection. Unexpectedly, infected IFN-gamma-/- mice showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities in the subacute phase. Destructive changes of hepatocytes were not observed. Administration of recombinant IFN-gamma protracted the survival time of IFN-gamma-/- mice after JHMV infection. These results demonstrate that IFN-gamma plays a critical role in viral clearance in JHMV infection. They also show that a resultant persistent JHMV infection induces another form of disease in IFN-gamma-/- mice, which bears a resemblance to feline infectious peritonitis in cats.


title: Serological survey of the Iriomote cat (Felis iriomotensis) in Japan.

text: The Iriomote cat (Felis iriomotensis) was first discovered on Iriomote Island in the Yaeyama Islands of Japan in 1965. Ten male and 11 female adult cats were captured during the 6 yr period from 1983 to 1988. These were examined for evidence of viral and mycoplasmal infections. Neither Mycoplasma sp. nor Ureaplasma sp. were detected in swab samples of oropharyngeal and urogenital regions. A foamy virus was isolated from the oropharyngeal swab of a female cat examined in 1988. Feline leukemia virus was not detected in any of the cats. All cats were negative for serum antibodies to feline panleukopenia virus, feline herpesvirus, feline immunodeficiency virus and rotavirus. Eleven of 19 (58%), 14 of 17 (82%) and 6 of 17 cats (35%) had serum antibodies against feline calicivirus, coronavirus and feline syncytium forming virus, respectively.


Proposed clinical guidance for orthodontists and orthodontic staff in the post-COVID-19 environment: a clinician's perspective.


title: [Metapneumoviruses--the "youngest" pathogens of respiratory tract infections in human].

text: Acute respiratory infections are the most common diseases in all age groups in the world. Lower respiratory infections are the main reason of death, hospitalization and antibiotic use in immunocomprised patients and/or patients with respiratory system chronic diseases. The leading role plays viruses: rhinoviruses, influenza and parainfluenza viruses, respiratory syncytial viruses (RSV), adnenoviruses and coronaviruses. The "youngest" pathogen in this group are human metapneumowiruses (hMPV), identified in 2001. They are the reason of infections in infants, older adults and immunocomprised patients. Manifestation of the infection can have a form from a self-limiting upper respiratory tract inflammation, through bronchitis (in adults), bronchiolitis (in infants) and pneumonitis (in infants and adults), and extremely of severe acute respiratory failure with a need of mechanical ventilation. The authores describe microbiological, epidemiological and clinical features on infection with hMPVs.


title: [Roles of the public-facility-turned temporary hospital in prevention and control of coronavirus disease 2019 in Wuhan, China and clinical experience in the hospital].

text: Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the public-facility-turned temporary hospital (PFTH) has played an important role in preventing the spread of the epidemic. Wuchang PFTH is the first one to put into clinical practice and the last one suspended in Wuhan. The National Emergency Medical Rescue Team of the Second Xiangya Hospital of Central South University, together with other 13 medical teams (841 medical staff in total), have fulfilled the task for the treatment of non-severe COVID-19 patients, without any medical staff infected. The first author of the article was the only pediatrician working in the Wuchang PFTH. The author describes and summarizes the features/functions, management/operations, and advantages/challenges of the PFTH, in order to provide reference for medical institutions and relevant departments to deal with public health emergencies.


docid: mhpdfrko

title: Asian venous thromboembolism guidelines: prevention of venous thromboembolism.

text: Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend prophylaxis with one of the following: low dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux or intermittent pneumatic compression (IPC). For the same group of patients at high risk of VTE, we recommend pharmacological or combination of pharmacological and mechanical prophylaxis. For patients undergoing major orthopedic surgeries like total hip replacement, total knee replacement and proximal hip fracture surgery, we recommend using one of the following: LMWH, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, warfarin or aspirin with IPC. For patients admitted to the hospital with acute medical illness and has moderate risk of VTE, we recommend prophylaxis with LDUH, LMWH or Fondaparinux. For the same group at high risk of VTE, we recommend combination of pharmacological and mechanical prophylaxis.


title: Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: host-dependent differences in proteolytic cleavage and cell fusion.

text: Cell fusion induced by infection with mouse hepatitis virus strain A59 (MHV-A59) varied markedly in extent and time course in four different murine cell lines. When inoculated at a multiplicity of 3 to 5 PFU per cell, the Sac-, L2, and DBT cell lines began to fuse by 7 h, were fused into confluent syncytia by 9 to 12 h, and peeled from the substrate by 10 to 14 h. These virulent virus-cell interactions were in striking contrast to the moderate interaction of MHV-A59 with the 17 Cl 1 cell line, in which only small syncytia were observed 18 h postinoculation, and greater than 50% of the cells remained unfused by 24 h. The yield of infectious virus produced by 17 Cl 1 cells was 10-fold higher than the yields from the other three cell lines. The processing of the nucleocapsid protein, the membrane glycoprotein E1, and the peplomeric glycoprotein E2 were found to differ significantly in the four cell lines. Since the E2 glycoprotein is responsible for virus-induced cell fusion, we attempted to correlate differences in cellular processing of E2 with differences in fusion of infected cells. The predominant intracellular form of E2 in all cell lines was the 180K species. Pulse-chase experiments showed that a small portion of the 17 Cl 1 cell-associated 180K E2 was cleaved by 1 h after synthesis to yield 90K E2, shown in the preceding paper to consist of two different glycoproteins called 90A and 90B (L. S. Sturman, C. S. Ricard, and K. V. Holmes, J. Virol. 56:904-911, 1985). This cleavage occurred shortly before the release of virions from cells, as shown by pulse-chase experiments. After budding at intracellular membranes, virions released into the medium by the four cell lines contained different ratios of 180K to 90K E2. Virions from Sac- cells, which contained 100% 90K E2, fused L2 cells rapidly without requiring virus replication, whereas virions from 17 Cl 1 cells, which had 50% 90K E2, required trypsin activation to induce rapid fusion (Sturman et al., J. Virol. 56:904-911, 1985). The addition of protease inhibitors to the medium markedly delayed L2 cell fusion induced by MHV infection. The extent of coronavirus-induced cell fusion does not depend solely upon the percent cleavage of the E2 glycoprotein by cellular proteases, since extensive fusion was induced by infection of L2 and DBT cells but not 17 Cl 1 cells, although all three cell lines cleaved E2 to the same extent.(ABSTRACT TRUNCATED AT 400 WORDS)


title: Current status of anti-SARS agents.

text: Severe acute respiratory syndrome (SARS) is a disease that has newly emerged in the 21st century, and is both severe and highly contagious. SARS first surfaced in late 2002 and spread within a few months from its origin in Guandong province, China, to more than 30 countries (World Health Organization, 2003). In this review, several antiviral substances shown to be active in vitro will be introduced and summarized in the order of the virus' replication steps; that is, binding to cellular receptor, fusion and entry to the cells, viral RNA replication and transcription, protein processing and so on. The possible clinical use of several synthetic peptides, including those that mimic the S-binding domain, the HR2 fusion protein and SARS proteinase substrates, will be discussed. Monoclonal antibodies (Mabs) and established drugs, such as interferons and HIV proteinase inhibitors, are also discussed in relation to anti-SARS clinical use.


title: End of life care.

text: NHS Employers has launched a short video to explain how staff at Salford Royal NHS Foundation Trust and Broughton House Care Home collaborate in the delivery of end of life care training. Rated outstanding by the Care Quality Commission for its end of life care services, the trust excels in supporting shared learning and reciprocal training through one-to-one education, role modelling, e-learning and classroom-based learning. A still from the video is shown above.


title: Prevalence of human Metapneumovirus (hMPV) in children with wheezing in Shiraz-Iran.

text: Human metapneumovirus (hMPV) infection plays an important role in the pediatric respiratory infections. The aim of this study was to determine the relationship between asthma and wheezing with hMPV in hospitalized children. Nasal pharyngeal swabs obtained from 120 children aged 1-60 months, hospitalized during a one year period, were tested for the hMPV by RT-PCR. HMPV was detected in 20 (16.6%) of patients suffering from wheezing. Some patients in addition to wheezing had asthma 10.8%. This infection occurred predominantly from October 2008 to September 2009.


title: Ochratoxin a: its cancer risk and potential for exposure.

text: Ochratoxin A (OA) is a naturally occurring mycotoxin known to contaminate a variety of foods and beverages. The cancer risk posed by OA was reviewed as relevant to human exposure, regulatory activities, and risk management efforts occurring worldwide, particularly in Europe. OA moves through the food chain and has been found in the tissues and organs of animals, including human blood and breast milk. Results from the National Toxicology Program's rodent bioassays show significantly increased incidence of mammary gland tumors in female rats and kidney tumors in male and female rats given OA orally. Liver tumors in female mice fed OA in the diet have also been observed. In humans, OA exposure has been most often associated with the kidney disease Balkan endemic nephropathy (BEN), symptoms of which include tumors of the kidney and urinary tract. No epidemiological studies have yet adequately evaluated the cancer risk of OA in human populations. Studies have shown OA to be genotoxic as well as immunotoxic, although its mode of action is not fully understood. Organizations and agencies in many countries are currently promulgating standards for OA in foods and beverages. Increased efforts in farm management and food safety are being made to mitigate the risks to public health posed by OA. The U.S. Food and Drug Administration (FDA) is currently evaluating data on OA levels in domestic and imported commodities but has not established official regulations or guidelines for OA in the U.S. food supply.


The growth of virus research 1928--1978.


title: Expression of Epstein-Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis.

text: Tumour cells of undifferentiated nasopharyngeal carcinoma (NPC) consistently harbour Epstein-Barr virus (EBV) genes. Expression of mRNA transcripts associated with EBV latency has been demonstrated in such cells. However, expression of EBV lytic genes has not been well elucidated, although various lines of evidence have suggested that there is EBV replication in NPC tumour cells. We have studied mRNA expression of representative EBV lytic genes by RT-PCR in nasopharynx biopsies obtained from NPC and control individuals. In both NPC and control biopsies, EBV lytic genes BZLF1, BALF2 and BCLF1 were detected readily. However, BRLF1 was detected in NPC biopsies only. The BRLF1 gene was then cloned and expressed in vitro, and the protein product, Rta, was used as an antigen to detect specific antibodies by immunoprecipitation in plasma samples obtained from NPC patients and healthy controls. IgG antibodies directed against Rta were detected in 44 of 53 NPC plasma samples (83.0%), but only in 1 of 53 control samples (1.9%). Furthermore, the antibody binding regions were found in the C-terminal two-thirds of Rta. This serological result confirms indirectly that BRLF1 is specifically expressed in NPC tumour cells. Rta might play an important role in NPC pathogenesis, considering its multiple functions in EBV replication and cell cycles. Moreover, the detection of IgG antibodies directed against Rta could be developed into a diagnostic parameter for NPC.


title: Clinical diagnostic approach to severe acute respiratory syndrome: an institution's experience.

text: OBJECTIVE To analyze diagnostic approach to severe acute respiratory syndrome (SARS) according to the diagnostic criteria issued by the Ministry of Health of China (MHC). METHODS The clinical data and the diagnostic results of 108 cases of SARS were retrospectively reviewed according to the MHC criteria. RESULTS There were 55 men and 53 women, with a median age of 34.5 years (range, 12 - 78 years). The interval between their first visit and clinical diagnosis was 3 days (range, 0 - 14 days). The diagnosis was made at the first visit in 7 (6.5%, 7/108) cases with a history of exposure to SARS patients and infiltrates on chest radiograph. Eighty-nine (82.4%) and 12 (11.1%) patients were categorized as probable cases and suspected cases respectively at their first visit and a clinical diagnosis of SARS was made subsequently. The interval between first visit and reaching the final diagnosis was 1 - 3 days in 72 (66.7%) cases and 4 days in 29 (26.9%) cases. The final diagnosis was made in 0 - 14 days (median, 2 days) for those (n = 59, 54.6%) with a history of close contact with SARS patients and 2 - 8 days (median, 3 days) for those (n = 49, 45.4%) living in Beijing but without such a history (P = 0.03). The chest radiograph was interpreted as unremarkable in 26 (24.1%) cases at their first visit, and the diagnosis was made in 4 days (range 2 - 8 days), which was significantly longer compared with other cases (P < 0.001). In patients without a history of close contact with SARS patients, all the five criteria were met after combination antibiotic therapy had failed. CONCLUSIONS A chest radiograph without infiltrates at the early stage of SARS is an important factor responsible for delayed diagnosis. In patients without a history of close contact with SARS cases, antibiotic effect was a major factor influencing doctors' diagnosis.


docid: rmxnndbc

title: Frequency and natural history of rhinovirus infections in adults during autumn.

text: Human rhinovirus (HRV) accounts for a significant portion of common-cold illness, with the peak incidence being in the early fall. Three hundred forty-six adults who had self-diagnosed colds of 48 h or less were enrolled in a study during September and October 1994 to determine the frequency and clinical course of HRV infections. Nasal wash specimens for viral culture and reverse transcription-PCR (RT-PCR) for HRV RNA and human coronavirus OC43 and 229E RNA detection were collected on enrollment, and participants recorded their symptoms twice daily for 14 days. Middle ear pressure (MEP) was measured with a digital tympanometer on days 1 and 7. Picornaviruses (224 HRV and 7 enterovirus isolates) were detected by culture in 67% (231 of 346) of the subjects. Among 114 samples negative by culture, HRV was detected by RT-PCR in 52 (46%) for an overall picornavirus infection rate of 82% (283 of 346 subjects). Among the remaining 62 negative samples, human coronavirus RNA was detected by RT-PCR in 5 patients, so that 288 (83%) of patients had documented viral infection. The first symptom noticed most often was sore throat (40%) in HRV culture- or PCR-positive patients and stuffy nose in HRV-negative patients (27%). No differences in symptom scores over time or in the presence of individual symptoms were noted between groups. The median duration of the cold episodes was 11 days in HRV culture-positive patients, 9.5 days in HRV RT-PCR-positive patients, and 11.5 days in HRV-negative patients. On enrollment, abnormal MEPs (< or = -100 or > or = +100 mm of H2O) were found for 21% of HRV culture-positive patients, 14% of HRV RT-PCR-positive patients, and 10% of HRV-negative patients. No important differences in the clinical course of HRV culture-positive, HRV culture-negative and RT-PCR-positive, or HRV-negative colds were found. These results represent the highest frequency of virologically confirmed natural colds to date and document the importance of rhinoviruses as the cause of colds during fall months.


title: Congenital nasal masses: CT and MR imaging features in 16 cases.

text: The imaging studies of 16 children with pathologically proved nasal encephaloceles (eight), nasal dermal sinuses/nasal dermoids (seven), and nasal cerebral heterotopias, more commonly known as nasal gliomas (one), were retrospectively reviewed and compared with normal control subjects to define the normal anatomy and analyze deformities caused by these lesions. Nasal encephaloceles were always identified as complex masses of mixed soft tissue and CSF intensity that were contiguous with intracranial structures. The nasal glioma appeared as a mixed-intensity mass that, on the basis of the CT scan, appeared to be continuous with intracranial structures. Nasal dermal sinuses could only be identified as they coursed through the skin and subcutaneous soft tissue. They could not be identified when intraosseous. Moreover, on CT and, particularly, on MR, a number of potential diagnostic pitfalls were encountered. The most important of these was the normal fat deposition that occurs within bone during normal maturation and during aeration of the frontal sinuses and nasal bones. These fatty changes can easily be mistaken for fatty tumors if they are not recognized as normal anatomic changes. Interestingly, the classic plain film findings for congenital nasal masses were present only in the encephaloceles and nasal glioma; dermoids and dermal sinuses showed none of the classic plain film findings. In the six patients who had both CT and MR, the masses were easily identified and characterized by each imaging method. Congenital nasal masses are well characterized by both CT and MR. It is important to understand the normal changes in the anatomy of the nasofrontal region in the pediatric age group to avoid false-positive diagnoses in this region.


title: [Research Advances in the Porcine Deltacoronavirus].

text: The deltacoronavirus is a new member of the subfamily Coronaviridae of the family Coronaviridae. Deltacoronaviruses can infect birds and mammals. Deltacoronaviruses were detected in early 2007 in Asian leopard cats and Chinese ferret badgers. In 2014, porcine deltacoronavirus (PDCoV) infection spread rapidly in the USA. Moreover, cell culture-adapted PDCoV has been obtained from infected piglets. Animal experiments have confirmed that the isolated PDCoV is highly pathogenic and causes severe diarrhea in piglets. Thus, the PDCoV can be considered to be a good model to study the deltacoronavirus. In this review, we discuss the etiology, epidemiology, pathogenicity, culture, and diagnostic methods of the PDCoV.


title: Using a Peritoneal Dialysis Access Simulator in Surgical Training for Nephrologists.

text: In Japan, peritoneal dialysis (PD) catheter insertion has been performed by both nephrologists and surgeons. However, nephrologists have fewer opportunities to train in the insertion procedure. We therefore used a PD access simulator to provide training in this operative technique for nephrologists. A PD access simulator developed by Terumo Medical Corporation was used for the training. The simulator uses a mannequin made of acrylic resin. The abdominal wall of a pig is attached to the abdominal area, and a plastic bag represents the abdominal cavity. The simulator enables the surgical procedure to be performed from skin incision to PD catheter insertion. Between October 2011 and December 2013, 3 supervising doctors used the simulator to guide 17 nephrologists with no experience through a PD catheter insertion. One-on-one training was provided in a single 2- or 3-hour session. In a questionnaire survey after the training, trainees gave high marks to the handling of surgical instruments, the environment of the operating room, and the surgical guidance during training. However, the supervising doctors required the ability to respond flexibly, because trainees had individual differences in skills. The PD access simulator might be useful for providing guided training in operative technique for PD catheter insertion.


title: Antibodies to selected viral disease agents in wild boars from the Czech Republic.

text: Blood samples were collected from wild boar (Sus scrofa) shot during the hunting season from 1999 to 2005 in the Czech Republic. Sera were tested by enzyme-linked immunosorbent assay for the presence of antibodies against classical swine fever virus (CSFV), swine vesicular disease virus (SVDV), Aujeszky's disease virus (ADV), and bovine viral diarrhea virus (BVDV). Indirect fluorescence antibody test was used for detection of antibodies against porcine circovirus type 2 (PCV-2) and transmissible gastroenteritis virus (TGEV). Antibodies against ADV, BVDV, PCV-2, and TGEV were detected in 30% (101 of 338), 1% (2 of 352), 43% (57 of 134), and 1% (1 of 134) of wild boars, respectively. Sera of 6,471 and 362 tested wild boars were negative for the presence of antibodies against CSFV and SVDV, respectively. This is the first survey of TGEV antibodies in wild boars and the first serologic survey of viral diseases in wild boars in the Czech Republic. Wild boars in the Czech Republic may act as a potential reservoir of ADV and thus have a role in the epidemiology of this disease.


title: Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

text: Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.


docid: vzfvfmwm

title: Correlates of HIV status among injection drug users in a border region of southern China and northern Vietnam.

text: This article presents an analysis of the correlates of HIV status among samples of injection drug users (IDUs) in Lang Son Province, Vietnam (n=348), and Ning Ming County, Guangxi Province, China (n=294), who were interviewed and tested for HIV antibody just before the start of a peer-based HIV prevention intervention in this border region. Participants were largely male, in their 20s, and single. Logistic regression analysis suggests that among Chinese IDUs, border-related factors (eg, living closer to the border, buying drugs across the border more frequently) and younger age are the best predictors of HIV positivity. In Vietnam, HIV status seems to drive behavior (eg, some risk reduction practices are predictive of HIV positivity). These differing patterns may reflect the fact that the intertwined epidemics of heroin injection and HIV began earlier and HIV prevalence has reached significantly higher levels in Lang Son than across the border in Ning Ming. Although border-related factors emerge as predictors in Ning Ming, more IDUs in Lang Son are HIV-positive and may be reacting behaviorally to that status. Their greater likelihood of engaging in risk reduction measures may reflect some combination of a belief that risk reduction can slow disease progression and an altruistic desire to avoid infecting others.


title: Serious electronic games as behavioural change interventions in healthcare-associated infections and infection prevention and control: a scoping review of the literature and future directions.

text: BACKGROUND The uptake of improvement initiatives in infection prevention and control (IPC) has often proven challenging. Innovative interventions such as 'serious games' have been proposed in other areas to educate and help clinicians adopt optimal behaviours. There is limited evidence about the application and evaluation of serious games in IPC. The purposes of the study were: a) to synthesise research evidence on the use of serious games in IPC to support healthcare workers' behaviour change and best practice learning; and b) to identify gaps across the formulation and evaluation of serious games in IPC. METHODS A scoping study was conducted using the methodological framework developed by Arksey and O'Malley. We interrogated electronic databases (Ovid MEDLINE, Embase Classic + Embase, PsycINFO, Scopus, Cochrane, Google Scholar) in December 2015. Evidence from these studies was assessed against an analytic framework of intervention formulation and evaluation. RESULTS Nine hundred sixty five unique papers were initially identified, 23 included for full-text review, and four finally selected. Studies focused on intervention inception and development rather than implementation. Expert involvement in game design was reported in 2/4 studies. Potential game users were not included in needs assessment and game development. Outcome variables such as fidelity or sustainability were scarcely reported. CONCLUSIONS The growing interest in serious games for health has not been coupled with adequate evaluation of processes, outcomes and contexts involved. Explanations about the mechanisms by which game components may facilitate behaviour change are lacking, further hindering adoption.


Fatal infection with influenza A (H5N1) virus in China.


title: Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions: structural analysis of the binding site.

text: CEACAM1 on leukocytic, endothelial, and epithelial cells functions in homophilic adhesion, tumor suppression, regulating cell adhesion and proliferation, and in heterophilic adhesion as a receptor for E-selectin and Neisseria meningiditis, Neisseria gonorrhoeae, Haemophilus influenzae, and murine coronaviruses. The 8 transmembrane isoforms of human CEACAM1 possess an extracellular N-terminal IgV domain, followed by variable numbers of IgC2 domains. To establish which key amino acids contribute specifically to CEACAM1 homophilic adhesion, exposed amino acids in the N-terminal domain of a soluble form of CEACAM1 were subjected to mutagenesis. Analyses of mutant proteins with conformationally dependent antibodies indicated that most mutations did not substantially affect the structural integrity of CEACAM1. Nevertheless, decreased adhesion was observed for the single mutants V39A or D40A (single-letter amino acid codes) in the CC' loop and for the triple mutants located in the GFCC'C" face of the N-terminal domain. Interestingly, whereas single mutations in R64 or D82 that are predicted to form a salt bridge between the base of the D and F beta strands close to the critical V39 and D40 residues also abolish adhesion, an amino acid swap (R64D and D82R), which maintains the salt bridge was without significant effect. These studies indicate that the CC' loop plays a crucial role in the homophilic adhesion of CEACAM1. They further predict that specific hydrophobic amino acid residues on the nonglycosylated GFCC'C" face of CEACAM1 N-terminal domain are not only involved in heterophilic interactions with Opa proteins and H influenzae, but are also critical for protein-protein interactions between 2 CEACAM1 molecules on opposing cells.


title: Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR.

text: Of 20 adults with acute community-acquired sinusitis (ACAS), rhinovirus was detected in specimens from 10 (50%) patients, including maxillary aspirates from 8 (40%) patients and nasal swabs from 9 (45%) patients, by reverse transcription-PCR (RT-PCR). Human coronavirus was detected by RT-PCR in nasal swabs from 3 of 20 patients but in no sinus secretions. These findings suggest that rhinovirus is an important cause of ACAS and that viral invasion of the sinus cavity itself may be a common event during the disease.


title: Pneumonia hospitalizations among young children before and after introduction of pneumococcal conjugate vaccine--United States, 1997-2006.

text: Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia hospitalizations and an important cause of bacteremia and meningitis, especially among young children and older adults. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed and the Advisory Committee on Immunization Practices formulated recommendations for its use in infants and children in February 2000. Vaccination coverage rapidly increased during the second half of 2000, in part through funding by CDC's Vaccines for Children program. Subsequently, active population- and laboratory-based surveillance demonstrated substantial reductions in invasive pneumococcal disease (IPD) among children and adults. In addition, decreases in hospitalizations and ambulatory-care visits for all-cause pneumonia also were reported. To gauge whether the effects of PCV7 on reducing pneumonia continue, CDC is monitoring pneumonia hospitalizations by using data from the Nationwide Inpatient Sample. This report provides an update for 2005 and 2006, the most recent years for which information is available. In 2005 and 2006, the incidence rates for all-cause pneumonia hospitalizations among children aged <2 years were 9.1 per 1,000 and 8.1 per 1,000, respectively. In 2006, the rate for all-cause pneumonia among children aged <2 years was approximately 35% lower than during 1997--1999. Most of this decrease occurred soon after the vaccine was licensed in 2000, and the rates have remained relatively stable since then. The rate for all-cause pneumonia among children aged 2--4 years did not change after PCV7 licensure and has remained stable. Continued monitoring of pneumonia-related hospitalizations among children is needed to track the effects of pneumococcal immunization programs.


title: Murine coronaviruses: isolation and characterization of two plaque morphology variants of the JHM neurotropic strain.

text: Two plaque-size variants of the neurotropic JHM strain of mouse hepatitis virus have been isolated from the virus stock after eight serial passages in suckling mouse brain. One variant, JHM-DL, produces large plaques, while the other, JHM-DS, produces small plaques in tissue culture. DS replicates more slowly, has a lower virus yield in vitro, and is less virulent for mice than DL. They also differ in their pathogenicity for mice: JHM-DL infection results in acute encephalomyelitis while JHM-DS infection results in demyelination. Oligonucleotide fingerprint analysis of the RNA genomes of these two variants revealed that they had almost identical genetic sequences. Each variant, however, had a unique oligonucleotide spot not found in the other. The unique spot of the large plaque variant, JHM-DL, was localized at approximately 3 to 5 kb from the 3' end, while the JHM-DS unique spot was mapped at 14 to 15 kb from the 3' end of the genome. We have further shown that these oligonucleotide changes are not correlated with the plaque morphology. These two viruses may be useful for studying the molecular basis of virus-induced demyelination.


title: Impact of fellowship during single-incision laparoscopic cholecystectomy.

text: BACKGROUND AND OBJECTIVES Minimally invasive surgery fellowship programs have been created in response to advancements in technology and patient's demands. Single-incision laparoscopic cholecystectomy (SILC) is a technique that has been shown to be safe and feasible, but this appears to be the case only for experienced surgeons. The purpose of this study is to evaluate the impact of minimally invasive surgery fellow participation during SILC. METHODS We reviewed data from our experience with SILC during 3 years. The cases were divided in two groups: group 1 comprised procedures performed by the main attending without the presence of the fellow, and group 2 comprised procedures performed with the fellow present during the operation. Demographic characteristics, comorbidities, indication for surgery, total surgical time, hospital length of stay, and complications were evaluated. RESULTS The cohort included 229 patients: 142 (62%) were included in group 1 and 87 (38%) in group 2. No differences were found in demographic characteristics, comorbidities, and indication for surgery between groups. The total surgical time was 34.4 ± 11.4 minutes for group 1 and 46.8 ± 16.0 minutes for group 2 (P < .001). The hospital length of stay was 0.89 0.32 days for group 1 and 1.01 ± 0.40 days for group 2 (P = .027). No intraoperative complications were seen in either group. There were 3 postoperative complications (2.1%) in group 1 and none in group 2 (P = .172). CONCLUSION Adoption of SILC during an established fellowship program is safe and feasible. A longer surgical time is expected during the teaching process.


title: Immunization of macaques with formalin-inactivated respiratory syncytial virus (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV infection.

text: Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. RSV vaccine development has been hampered by results of clinical trials in the 1960s, when formalin-inactivated whole-RSV preparations adjuvated with alum (FI-RSV) were found to predispose infants for enhanced disease following subsequent natural RSV infection. We have reproduced this apparently immunopathological phenomenon in infant cynomolgus macaques and identified immunological and pathological correlates. Vaccination with FI-RSV induced specific virus-neutralizing antibody responses accompanied by strong lymphoproliferative responses. The vaccine-induced RSV-specific T cells predominantly produced the Th2 cytokines interleukin-13 (IL-13) and IL-5. Intratracheal challenge with a macaque-adapted wild-type RSV 3 months after the third vaccination elicited a hypersensitivity response associated with lung eosinophilia. The challenge resulted in a rapid boosting of IL-13-producing T cells in the FI-RSV-vaccinated animals but not in the FI-measles virus-vaccinated control animals. Two out of seven FI-RSV-vaccinated animals died 12 days after RSV challenge with pulmonary hyperinflation. Surprisingly, the lungs of these two animals did not show overt inflammatory lesions. However, upon vaccination the animals had shown the strongest lymphoproliferative responses associated with the most pronounced Th2 phenotype within their group. We hypothesize that an IL-13-associated asthma-like mechanism resulted in airway hyperreactivity in these animals. This nonhuman primate model will be an important tool to assess the safety of nonreplicating candidate RSV vaccines.


title: Monoclonal antibodies differentiate between the haemagglutinating and the receptor-destroying activities of bovine coronavirus.

text: A relatively simple and sensitive method is described which enables the effect of monoclonal antibodies (MAbs) on the receptor-destroying enzyme (RDE) and the haemagglutination (HA) activity of bovine coronavirus (BCV) to be analysed in one assay. A lysate of HRT-18 cells infected with the L9 strain of BCV was found to have a higher RDE:HA ratio than purified virus. At 4 degrees C the lysate induced an HA pattern which completely disappeared upon raising of the temperature to 37 degrees C. This L9-infected cell lysate was used to determine the HA inhibition (HAI) titres of MAbs directed against the surface glycoproteins S and HE of BCV. Thereafter, the test plates were incubated at 37 degrees C to enable the ability of the MAbs to prevent elution of virus from BCV-erythrocyte complexes to be assessed. No inhibition of RDE was detectable with MAbs against glycoprotein S, which had HAI titres ranging from 1:16 to 1:128. On the other hand, MAbs directed against glycoprotein HE had similar HAI titres, but they inhibited elution of 8 HA units of BCV at titres of up to 1:65,000.


title: [Pediatric impact of COVID-19].

text: Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.


title: Inhibition of hepatitis C virus replication by arsenic trioxide.

text: Hepatitis C virus (HCV) is a serious global problem, and present therapeutics are inadequate to cure HCV infection. In the present study, various antiviral assays show that As2O3 at submicromolar concentrations is capable of inhibiting HCV replication. The 50% effective concentration (EC50) of As2O3 required to inhibit HCV replication was 0.35 microM when it was determined by a reporter-based HCV replication assay, and the EC50 was below 0.2 microM when it was determined by quantitative reverse transcription-PCR analysis. As2O3 did not cause cellular toxicity at this concentration, as revealed by an MTS [3-(4,5-dimethylthiozol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. A combination of As2O3 and alpha interferon exerted synergistic effects against HCV, as revealed by a multiple linear logistic model and isobologram analysis. Furthermore, in an alternative HCV antiviral system that may recapitulate additional steps involved in HCV infection and replication, As2O3 at 0.3 microM totally abolished the HCV signal, whereas alpha interferon at a high dose (5,000 IU/ml) only partially suppressed the HCV signal. The study highlights the indications for use of a novel class of anti-HCV agent. Further elucidation of the exact antiviral mechanism of As2O3 may lead to the development of agents with potent activities against HCV or related viruses.


Recycling the past.


docid: iitsfoap

title: How to allocate intensive care resources during the COVID-19 pandemic: medical triage or a priori selection?


title: [Dealing with COVID-19-associated coagulopathy].

text: COVID-19 is associated with a high prevalence of activation of the coagulation cascade. It has been suggested that this so-called COVID-19-associated coagulopathy is predictive of a poor outcome and of mortality. Consensus documents on how to manage patients with COVID-19-associated coagulopathy are based on the limited number of mainly retrospective studies that is currently available, and for this reason the recommendations are not always consistent with one another. In this article, we review the first studies into COVID-19-associated coagulopathy and give the most important do's and don'ts for diagnostics and the daily management of coagulopathy and the prevention of complications in patients with, or with strongly-suspected, COVID-19 in Dutch clinical practice.


title: Isolation of coronavirus envelope glycoproteins and interaction with the viral nucleocapsid.

text: The two envelope glycoproteins and the viral nucleocapsid of the coronavirus A59 were isolated by solubilization of the viral membrane with Nonidet P-40 at 4 degrees C followed by sucrose density gradient sedimentation. Isolated E2 consisted of rosettes of peplomers, whereas E1, the membrane glycoprotein, was irregular and amorphous. Under certain conditions significant interactions occurred between components of Nonidet P-40-disrupted virions. Incubation of the Nonidet P-40-disrupted virus at 37 degrees C resulted in formation of a complex between one of the viral glycoproteins, E1, and the viral nucleocapsid. This was caused by a temperature-dependent conformational change in E1, resulting in aggregation of E1 and interaction with the viral RNA in the nucleocapsid. E1 also bound rRNA. The E1-nucleocapsid complexes can be distinguished on sucrose and Renografin density gradients from native viral nucleocapsids. The separation of the membrane glycoprotein E1 from the peplomeric glycoprotein E2 permitted preparation of antisera against these isolated proteins. A model is proposed for the arrangement of the three major structural proteins in the coronavirus A59 virion in relation to the viral envelope and RNA.


title: Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon.

text: Hepatitis C virus non-structural NS5A protein inhibits epidermal growth factor (EGF)-stimulated activation of the Ras-ERK mitogen-activated protein kinase pathway at a point upstream of Ras activation. To determine the mechanism of this inhibition, the events occurring between the EGF receptor and Ras in Huh-7 cells harbouring the HCV subgenomic replicon were investigated. It was shown that, following EGF stimulation, these cells exhibited decreased EGF receptor tyrosine phosphorylation, aberrant recruitment of the adaptor proteins ShcA and Grb2 to the EGF receptor, reduced phosphorylation of ShcA and reduced Ras activation in comparison with control cells. These data are consistent with effects of NS5A and/or other components of the replicon on multiple events occurring upstream of Ras.


title: Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus.

text: The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.


title: Consensus statement of the consortium for LESS cholecystectomy.

text: Many surgeons attempting Laparo-Endoscopic Single Site (LESS) cholecystectomy have found the operation difficult, which is inconsistent with our experience. This article is an attempt to promote a standardized approach that we feel surgeons with laparoscopic skills can perform safely and efficiently. This is a four-trocar approach consistent with the four incisions utilized in conventional laparoscopic cholecystectomy. After administration of general anesthesia, marcaine is injected at the umbilicus and a 12-mm vertical incision is made through the already existing anatomical scar of the umbilicus. A single four-trocar port is inserted. A 5-mm deflectable-tip laparoscope is placed through the trocar at the 8 o'clock position, a bariatric length rigid grasper is inserted through the trocar at the 4 o'clock position (to grasp the fundus), and a rigid bent grasper is placed through the 10-mm port (to grasp the infundibulum). This arrangement of the instruments promotes minimal internal and external instrument clashing with simultaneous optimization of the operative view. This orientation allows retraction of the gallbladder in a cephalad and lateral direction, development of a window between the gallbladder and the liver which promotes the "critical view" of the cystic duct and artery, and provides triangulation with excellent visualization of the operative field. The operation is concluded with diaphragmatic irrigation of marcaine solution to minimize postoperative pain. Standardization of LESS cholecystectomy will speed adoption, reduce intraoperative complications, and improve the efficiency and safety of the approach.


Protecting yourself and your patients from COVID-19 in eye care.


title: Retroperitoneoscopic adrenalectomy in pheochromocytoma.

text: Since the first laparoscopic adrenalectomy, the technique has evolved and it has become the standard of care for many adrenal diseases, including pheochromocytoma. Two laparoscopic accesses to the adrenal have been developed: transperitoneal and retroperitoneal. Retroperitoneoscopic adrenalectomy may be recommended for the treatment of pheochromocytoma with the same peri-operative outcomes of the transperitoneal approach because it allows direct access to the adrenal glands without increasing the operative risks. Although technically more demanding than the transperitoneal approach, retroperitoneoscopy can shorten the mean operative time, which is critical for cases with pheochromocytoma where minimizing the potential for intra-operative hemodynamic changes is essential. Blood loss and the convalescence time can be also shortened by this approach. There is no absolute indication for either the transperitoneal or retroperitoneal approach; however, the latter procedure may be the best option for patients who have undergone previous abdominal surgery and obese patients. Also, retroperitoneoscopic adrenalectomy is a good alternative for treating cases with inherited pheochromocytomas, such as multiple endocrine neoplasia type 2A, in which the pheochromocytoma is highly prevalent and frequently occurs bilaterally.


title: Calculated decisions: COVID-19 calculators during extreme resource-limited situations.

text: In the near future, clinicians may face scenarios in which there are not have enough resources (ventilators, ECMO machines, etc) available for the number of critically sick COVID-19 patients. There may not be enough healthcare workers, as those who are positive for COVID-19 or those who have been exposed to the virus and need to be quarantined. During these worst-case scenarios, new crisis standards of care and thresholds for intensive care unit (ICU) admissions will be needed. Clinical decision scores may support the clinician's decision-making, especially if properly adapted for this unique pandemic and for the patient being treated. This review discusses the use of clinical prediction scores for pneumonia severity at 3 main decision points to examine which scores may provide value in this unique situation. Initial data from a cohort of over 44,000 COVID-19 patients in China, including risk factors for mortality, were compared with data from cohorts used to study the clinical scores, in order to estimate the potential appropriateness of each score and determine how to best adjust results at the bedside.


The Ethics of Patient Risk Modification Prior to Elective Joint Replacement Surgery.


title: Marionette method for transumbilical single-incision, two-trocar laparoscopic cholecystectomy: a new, simple technique.

text: BACKGROUND/AIMS Single-incision laparoscopic cholecystectomy (SILC) has recently become a topic of interest among types of minimally invasive surgery. METHODOLOGY We developed a novel "marionette method"technique for performing SILC. Two 5 mm trocars were placed through a 1.5 cm transumbilical incision. In addition, a nylon suture with a laparoscopic sliding knot was used to tighten the fundus of the gallbladder and was thereafter suspended with this nylon suture. The neck of the gallbladder was tightened by means of a loop type retractor, to enable adequate visualization of the triangle of Calot. Dissection was performed as a conventional laparoscopic cholecystectomy using standard straight laparoscopic instruments. RESULTS All 20 patients successfully underwent a single-incision, two-trocar laparoscopic cholecystectomy performed using the marionette method. The mean operative time was 119 min. There were no complications. CONCLUSIONS The marionette method can provide good tension and an appropriate laparoscopic view with a suitable surgical field for safely performing a dissection at the triangle of Calot during SILC.


title: Influence of dietary tannic acid and polyethylene glycol on growth and intestinal D-xylose absorption of broiler cockerels and activity of serum enzymes.

text: 1. In an experiment on broiler cockerels, the influence of tannic acid (TA) and polyethylene glycol (PEG) on body weight gain (BWG), feed conversion ratio (FCR), weight of intestine and liver, the activities of serum enzymes LDH, AST, ALT and intestinal absorption function were investigated. 2. Broiler cockerels were given either a commercial diet alone (control group) or a commercial diet with TA (20 g/kg), PEG (10 g/kg) or TA plus PEG (20 + 10 g/kg), for 10 d. 3. On the last day of the experiment, all birds and remaining feed were weighed individually and a sample of blood was taken to measure the serum activities of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The capacity of intestinal cells for the absorption of D-xylose was measured. Finally all birds were killed humanely and the intestine and liver were weighed. 4. The results showed that TA significantly reduced BWG and FCR, as well as the activity of LDH, AST and ALT. 5. TA also increased the relative weight of the intestine. Adding PEG alone had no effect on any of the measured parameters. 6. However, PEG improved significantly BWG, FCR and the activity of LDH and AST of TA-fed birds. 7. The plasma D-xylose concentration of experimental birds was similar for all dietary treatments most likely because of temporal separation between feeding the dietary TA and administering the D-xylose. 8. It was concluded that the presence of tannins in the GI lumen of the bird was necessary to affect the processes involved in the absorption of simple sugars such as D-xylose, at the level of intestinal absorptive cells.


title: Evolution of pulmonary pathology in severe acute respiratory syndrome.

text: BACKGROUND AND PURPOSE Severe acute respiratory syndrome (SARS) is characterized by fever with rapid progression to acute respiratory distress and it is associated with substantial morbidity and mortality. Transmission patterns suggest spread by respiratory droplet or close person-to-person contact. To elucidate the correlation of clinical presentation to the pathogenesis and course of the disease, we reviewed the pulmonary pathologic specimens of SARS patients taken at different stages of the disease. METHODS Four "probable" cases of SARS were studied. SARS-associated coronavirus (SARS-CoV) infection was demonstrated using reverse transcriptase-polymerase chain reaction in all 4 patients. The pulmonary specimens were taken on day 7 after symptom onset in patient 1, day 11 in patient 2, day 17 in patient 3, and day 21 in patient 4. RESULTS The autopsy lung tissue from patient 1, who died 7 days after symptoms onset due to the complication of acute myocardial infarction, revealed mild histologic change in the lung. Only focal pulmonary edema or hemorrhage was seen. In the second patient, who died 11 days after symptom onset, severe acute alveolar damage was characterized by patchy or diffuse lung edema, hyaline membrane formation, and scarce lymphocytic infiltration. The lymphocytes were mostly CD3-positive and CD20-negative. In the third patient, biopsy specimen taken 17 days after symptom onset showed patches of organizing pneumonia with reactive fibroblastic proliferation, more abundant type II pneumocytes and clustering of CD68-positive macrophages within the alveolar spaces. Few CD68-positive syncytial multinucleated giant cells were also seen in the specimens but no viral inclusion body could be identified in these cells. The lung biopsy specimen from patient 4 taken 21 days after symptom onset showed characteristics of the fibrotic stage, with significant myofibroblastic proliferation in the alveolar space and interstitium resulting in loss of pulmonary architecture. The number of CD3-positive lymphocytes and of CD68-positive macrophages in this specimen from a patient in the fibrotic phase of diffuse alveolar damage (DAD) whose condition deteriorated was less than in the specimen from case 3 who was in the early proliferative phase of DAD and eventually recovered. CONCLUSIONS The histologic evolution of SARS coincided with the different stages of DAD: acute, proliferative organizing, and fibrotic stages. SARS cannot be differentiated from the other etiologies of DAD by morphologic examination alone. The absence of DAD does not rule out the possibility of SARS-CoV infection, particularly in the early stage of the disease.


title: In vitro inhibition of SARS virus replication by human interferons.

text: Four different types of human interferon, interferon-beta (IFN-beta), recombinant IFN-alpha2a and IFN-alpha2b and natural IFN-alpha were tested for antiviral activity against SARS-coronavirus. The experiments were performed using in vitro cultivated monkey Vero E6 cells. IFN-beta was found to be the most highly active antiviral agent, followed by natural IFN-alpha, whereas the 2 recombinant IFN-alpha2 species were poorly active in the system used. These results suggest that IFN-beta as well as natural IFN-alpha may be used for the treatment of SARS.


title: Porcine reproductive and respiratory syndrome: NEB-1 PRRSV infection did not potentiate bacterial pathogens.

text: A 2-phase study was conducted to evaluate the ability of the NEB-1 strain of porcine reproductive and respiratory syndrome virus (PRRSV) to potentiate common bacterial pathogens of swine. In phase I, 25 of 50 4-5-week-old specific-pathogen-free (SPF) pigs were exposed to NEB-1 PRRSV (day 0). Seven days after virus inoculation, 8 groups received 1 of 4 bacterial pathogens: Haemophilus parasuis, Streptococcus suis, Salmonella cholerasuis, and Pasteurella multocida. The ability of NEB-1 PRRSV to produce clinical disease, viremia, neutralizing antibody, gross and microscopic lesions and to potentiate bacterial pathogens was assessed. Response to NEB-1 PRRSV was similar among inoculated pigs; prolonged hyperthermia, lethargy, mild to moderate dyspnea, and cutaneous erythema were consistent clinical signs. No clinical differences were observed in groups after bacterial challenge. Virus was isolated from serum at weekly intervals through the end of the study, and all PRRSV-inoculated pigs had seroconverted by study termination. Two of 5 pigs died in non-PRRSV-inoculated groups challenged with H. parasuis and Streptococcus suis. Mortality in PRRSV-infected pigs was limited to 1 of 5 pigs from the Salmonella cholerasuis-challenged group. Gross lesions were seen in pigs dying after inoculation in H. parasuis- and Streptococcus suis-inoculated groups, in Salmonella cholerasuis- and P. multocida-challenged pigs, and in 1 non-PRRSV-inoculated control pig. Microscopic lesions consisted of mild to moderate proliferative interstitial pneumonia, nonsuppurative myocarditis, lymphoid hyperplasia, and nonsuppurative encephalitis in PRRSV-inoculated pigs. Findings in phase I indicated that NEB-1 PRRSV does not potentiate bacterial disease while inducing consistent clinical signs, viremia, seroconversion, and microscopic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Wildlife population management: are contraceptive vaccines a feasible proposition?

text: To minimize human-animal conflicts for habitation and burden of zoonotic diseases, it is imperative to develop new strategies for wildlife population management. In this direction, contraceptive vaccines eliciting immune response against hormones/proteins critical for reproduction have emerged as one of the promising options. Contraceptive vaccines based on neutralization of gonadotropin releasing hormone (GnRH) have been used for inhibition of fertility in various species such as wild horses, white-tailed deer, pigs, cats, dogs etc. It has been used for immunocastration of male pigs to improve meat quality. However, additional safety studies of GnRH vaccine will be needed in light of presence of its receptor at extra-pituitary sites. Native porcine zona pellucida (PZP)-based contraceptive vaccines have shown their utility in the management of the population of both captive and free-ranging wild horses and white-tailed deer. Long-term use of the PZP-based contraceptive vaccines has also demonstrated their safety. Ideally single injection of the contraceptive vaccine should elicit long lasting immune response and desired contraceptive efficacy, which will require development of novel vaccine delivery platforms and more potent adjuvants.


title: Detection of Feline leukemia virus in the endangered Iberian lynx (Lynx pardinus).

text: Feline retroviruses are rarely reported in lynx species. Twenty-one Iberian lynx (Lynx pardinus) blood and tissue samples collected from Doñana National Park and Los Villares (Sierra Morena) in southern Spain during 1993-2003 were analyzed by polymerase chain reaction to amplify nucleic acids from feline retroviruses. Six samples were positive for Feline leukemia virus (FeLV), but no samples tested positive for Feline immunodeficiency virus. The BLAST analysis indicated that 5 of the 6 sequences were closely related to FeLV strain Rickard subgroup A, whereas 1 sequence was identical to FeLV. To the authors' knowledge, this is the first report of FeLV in the endangered Iberian lynx.


title: Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein.

text: Like most coronaviruses, the coronavirus mouse hepatitis virus (MHV) exhibits strong species specificity, causing natural infection only in mice. MHV-A59 virions use as a receptor a 110- to 120-kDa glycoprotein (MHVR) in the carcinoembryonic antigen (CEA) family of glycoproteins (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; and R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). The role of virus-receptor interactions in determining the species specificity of MHV-A59 was examined by comparing the binding of virus and antireceptor antibodies to cell lines and intestinal brush border membranes (BBM) from many species. Polyclonal antireceptor antiserum (anti-MHVR) raised by immunization of SJL/J mice with BALB/c BBM recognized MHVR specifically in immunoblots of BALB/c BBM but not in BBM from adult SJL/J mice that are resistant to infection with MHV-A59, indicating a major difference in epitopes between MHVR and its SJL/J homolog which does not bind MHV (7). Anti-MHVR bound to plasma membranes of MHV-susceptible murine cell lines but not to membranes of human, cat, dog, monkey, or hamster cell lines. Cell lines from these species were resistant to MHV-A59 infection, and only the murine cell lines tested were susceptible. Pretreatment of murine fibroblasts with anti-MHVR prevented binding of radiolabeled virions to murine cells and prevented virus infection. Solid-phase virus-binding assays and virus overlay protein blot assays showed that MHV-A59 virions bound to MHVR on intestinal BBM from MHV-susceptible mouse strains but not to proteins on intestinal BBM from humans, cats, dogs, pigs, cows, rabbits, rats, cotton rats, or chickens. In immunoblots of BBM from these species, both polyclonal and monoclonal antireceptor antibodies that block MHV-A59 infection of murine cells recognized only the murine CEA-related glycoprotein and not homologous CEA-related glycoproteins of other species. These results suggest that MHV-A59 binds to a mouse-specific epitope of MHVR, and they support the hypothesis that the species specificity of MHV-A59 infection may be due to the specificity of the virus-receptor interaction.


title: Commercial aviation in-flight emergencies and the physician.

text: Commercial aviation in-flight emergencies are relatively common, so it is likely that a doctor travelling frequently by air will receive a call for help at some stage in their career. These events are stressful, even for experienced physicians. The present paper reviews what is known about the incidence and types of in-flight emergencies that are likely to be encountered, the international regulations governing medical kits and drugs, and the liability, fitness and indemnity issues facing 'Good Samaritan' medical volunteers. The medical and aviation literature was searched, and information was collated from airlines and other sources regarding medical equipment available on board commercial aircraft. Figures for the incidence of significant in-flight emergencies are approximately 1 per 10-40 000 passengers, with one death occurring per 3-5 million passengers. Medically related diversion of an aircraft following an in-flight emergency may occur in up to 7-13% of cases, but passenger prescreening, online medical advice and on-board medical assistance from volunteers reduce this rate. Medical volunteers may find assisting with an in-flight emergency stressful, but should acknowledge that they play a vital role in successful outcomes. The medico-legal liability risk is extremely small, and various laws and industry indemnity practices offer additional protection to the volunteer. In addition, cabin crew receive training in a number of emergency skills, including automated defibrillation, and are one of several sources of help available to the medical volunteer, who is not expected to work alone.


title: Modelling strategies for controlling SARS outbreaks.

text: Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.


title: [Anesthesia management in cesarean section for patient with COVID-19: a case report].

text: Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.


title: Characterization of the human coronavirus 229E (HCV 229E) gene 1.

text: The sequence of the HCV 229E gene 1 has been determined and compared with the homologous sequences of the murine hepatitis virus and the avian infectious bronchitis virus. The coding sequence of gene 1 is 20,273 nucleotides in length. Within this coding region are two large open reading frames, ORF 1a (4,086 codons) and ORF 1b (2,687 codons) which overlap by 40 nucleotides. In the overlapping region, the genomic RNA can be folded into a pseudoknot structure, an element which is known to mediate -1 ribosomal frame-shifting in other coronaviruses. Assuming that -1 frame-shifting occurs at the HCV sequence UUUAAAC (nucleotides 12,514-12,520), the ORF 1a - ORF 1b product is predicted to be 6,758 amino acids in length. Our sequence analysis of the HCV 229E gene 1 has revealed a high degree of similarity within the ORF 1b of HCV, MHV and IBV, whereas ORF 1a is much less conserved. Elements which are believed to be necessary for specific (e.g. frame-shifting) and general (e.g. NTP-binding/helicase) transcriptional functions have been identified. This study completes the genomic sequence of HCV 229E which is 27.27 kb long and one of the largest known RNA genomes.


title: Effect of daily sedative interruption on sleep stages of mechanically ventilated patients receiving midazolam by infusion.

text: Daily sedative interruption (DSI) may reduce excessive sedation and shorten the duration of mechanical ventilation. It is not clear, however, how DSI affects sleep characteristics. For patients receiving mechanical ventilation, we compared the effect on sleep quality of DSI and continuous sedation (CS). Twenty-two mechanically ventilated patients who were receiving midazolam by infusion were randomly assigned to two groups, DSI (n = 11) or CS (n = 11). In the DSI group, sedatives were interrupted until the patients awoke and expressed discomfort, after which midazolam or opioids were administered intermittently as needed during the daytime (0600 to 2100 hours); during the night (2100 to 0600) midazolam was administered intravenously to maintain Ramsay sedation scale 4 to 5. In the CS group, the sedatives were titrated to obtain Ramsay sedation scale 4 to 5 throughout the day. The polysomnography of each patient was recorded continuously over a 24 hour period. Sleep stages were analysed using Rechtschaffen and Kales criteria. In the DSI group, the amount of stage 3 and 4 non-rapid eye movement sleep (slow wave sleep) was longer (6 vs 0 minutes, P = 0.04) and rapid eye movement sleep was longer than in CS (54 vs 0 minutes, P = 0.02). In the CS group, total sleep time during night-time was longer (8.7 vs 7.3 hours, P = 0.047) and frequency of arousal was lower (2.2 vs 4.4 event/hour, P = 0.03) than those in the DSI group. All mechanically ventilated patients demonstrated abnormal sleep architecture, but, compared with CS, DSI increased the amount of slow wave sleep and rapid eye movement sleep.


title: Barriers to at-home-preparedness in public health employees: implications for disaster preparedness training.

text: OBJECTIVES To assess "at-home" preparedness and barriers to preparedness in a cohort of public health employees. METHOD Conducted a cross-sectional survey involving 100 employees attending emergency preparedness training that emphasized incident command training and included a segment on "at-home" preparedness. RESULTS Fifteen percent of participants were rated as "better prepared," and only 8% of participants would be considered "most prepared." There was no relationship between the concern for bioterrorism and other disasters and preparedness. The principal barrier involved challenges in getting the task done versus lack of desire or knowledge. CONCLUSIONS There is great potential for distraction of public health workers during an emergent event if they are not prepared at home and have concern for family members. At-home preparedness training efforts that emphasize what should be done and why are likely to have limited impact on changing behavior. Strategies that ensure that small steps are taken are likely to be more successful.


title: Baseline assessment of ophthalmic parameters in the greater one-horned rhinoceros (Rhinoceros unicornis).

text: Five healthy captive greater one-horned rhinoceroses (Rhinoceros unicornis) were evaluated with standing sedation (detomidine hydrochloride 20-30 mg and butorphanol tartrate 50-60 mg per animal) to determine baseline values for tear production, intraocular pressure (IOP), conjunctival flora, and ocular anatomy using brightness mode transpalpebral ultrasonography with a 4- to 7-MHz broadband curvilinear transducer. The mean Schirmer tear test I value was 18.2 ± 3.49 mm/min. The mean IOP measured using applantation tonometry was 31.2 ± 6.62 mm Hg. Ocular biometry measurements were the following: axial length 2.61 ± 0.11 cm; corneal thickness 0.13 ± 0.01 cm; anterior segment depth 0.28 ± 0.06 cm; lens depth 0.70 ± 0.11 cm; and posterior segment depth 1.46 ± 0.13 cm. These values indicate that the globe is smaller than that of the domestic horse. All eight conjunctival swabs cultured bacterial and fungal microorganisms, with the most common being Staphylococcus spp. (57%). All bacterial isolates were considered to be commensal organisms due to the presence of mixed bacterial populations and lack of clinical signs of ocular disease. The data collected in this study should provide veterinarians with baseline information to assist in the diagnosis of ophthalmic conditions in the greater one-horned rhinoceros.