title: Diurnal variation in the symptoms of colds and influenza.

text: The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings. Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.


[When you are sick].


title: Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac Arrest.

text: OBJECTIVES To determine the longitudinal changes in functional outcome and compare ordinal outcome scale assessments in comatose cardiac arrest survivors. DESIGN Prospective observational study of comatose cardiac arrest survivors. Subjects who survived to 1 month were included. SETTING Academic medical center ICU. PATIENTS Ninety-eight consecutive patients who remained comatose after resuscitation from cardiac arrest; 45 patients survived to 1 month. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients' functional neurologic outcomes were assessed by phone call or in-person clinic visit at 1, 3, 6, and 12 months postcardiac arrest using the modified Rankin Scale, Glasgow Outcome Scale, and Barthel Index. A "good" outcome was defined as modified Rankin Scale 0-3, Barthel Index 70-100, and Glasgow Outcome Scale 4-5. Changes in dichotomized outcomes and shifts on each outcome scale were analyzed. The mean age of survivors was 51 ± 19 years and 18 (40%) were women. Five (19%) out of 26 patients with data available at all timepoints improved to good modified Rankin Scale outcome and none worsened to poor outcome between postarrest months 1 and 6 (p = 0.06). Thirteen patients (50%) improved on the modified Rankin Scale by 1-3 points and four (15%) worsened by 1-2 points between months 1 and 6 (overall improvement by 0.5 points; 95% CI, 0-1; p = 0.04). From postarrest months 6 to 12, there was no change in the number of patients with good versus poor outcomes. The modified Rankin Scale and Barthel Index were more sensitive to detecting changes in outcome than the Glasgow Outcome Scale. CONCLUSIONS In initially comatose cardiac arrest survivors, improvements in functional status occur over the first 6 months after the event. There was no significant change in outcome between postarrest months 6 and 12. The modified Rankin Scale is a sensitive outcome scale in this population.


title: Rapid de novo aneurysm formation after clipping of a ruptured middle cerebral artery aneurysm in an infant with an MYH11 mutation.

text: The authors report the case of a previously healthy 6-month-old girl who presented with right arm and leg stiffening consistent with seizure activity. An initial CT scan of the head demonstrated acute subarachnoid hemorrhage in the basal cisterns extending into the left sylvian fissure. Computed tomography angiography demonstrated a 7 × 6 × 5-mm saccular aneurysm of the inferior M2 division of the left middle cerebral artery. The patient underwent left craniotomy and microsurgical clip ligation with wrapping of the aneurysm neck because the vessel appeared circumferentially dysplastic in the region of the aneurysm. Postoperative angiography demonstrated a small remnant, sluggish distal flow, but no significant cerebral vasospasm. Fifty-five days after the initial aneurysm rupture, the patient presented again with an acute intraparenchymal hemorrhage of the left anterior temporal lobe. Angiogram revealed a circumferentially dysplastic superior division of the M2 branch, with a new 5 × 4-mm saccular aneurysm distinct from the first, with 2 smaller aneurysms distal to the new ruptured aneurysm. Endovascular parent vessel occlusion with Onyx was performed. Genetic testing revealed a mutation of the MYH11. To the authors' knowledge, this is the first report of rapid de novo aneurysm formation in an infant with an MYH11 mutation. The authors review the patient's clinical presentation and management and comprehensively review the literature on this topic.


Provision of Service During the Covid-19 Pandemic


title: Tonsillectomy healing.

text: OBJECTIVES We performed a prospective observation study in an outpatient surgical and office setting to compare human post-tonsillectomy healing to human cutaneous wound healing and to established animal models of oral healing. METHODS Fourteen teenaged patients underwent planned tonsillectomy. Intraoral digital photographs were collected at the time of tonsillectomy, during the management of complications, and at postoperative office visits. Serial intraoral photographs of one patient were taken at 48-hour intervals from the time of surgery until postoperative day 17. RESULTS Intraoral photographs from the days after tonsillectomy revealed a pattern of inflammation and healing that closely paralleled that in human skin and in canine and porcine oral wound models. CONCLUSIONS Edema and pain are greatest immediately after surgery, probably as a result of thermal effects and expression of inflammatory mediators that stimulate pharyngeal nociceptors. Pain gradually decreases over time, with an increase in analog pain measures on postoperative days 3 to 5 corresponding to the maximal wound inflammation documented in experimental models. Epithelial ingrowth beneath a fibrin clot begins shortly after wounding. Separation of the fibrin clot about 7 days after surgery exposes vascular stroma. Involution of the vascular stroma and completion of epithelial coverage correlate with decreased pain levels and a lessened risk of bleeding.


title: Bridging distance and culture with a cyberspace method of qualitative analysis.

text: This article describes a qualitative research method that weds the cyberspace technology of e-mail with a phenomenological research approach. Examples are provided from 2 separate data sets. One data set explored the meaning of health for Japanese elders; the second explored Chinese nurses' experience of taking care of patients with severe acute respiratory syndrome. Lessons learned while using the cyberspace method are discussed, including guidance for organizing a long-distance research team, the central place of trust, and the time when e-mail communication demands to be supplemented with face-to-face interaction. The potential for bridging distance and culture with this cyberspace method is introduced for consideration and critique.


title: Subcellular localization of herpes simplex virus type 1 UL51 protein and role of palmitoylation in Golgi apparatus targeting.

text: The herpes simplex virus type 1 (HSV-1) UL51 gene products are virion-associated phosphoproteins with apparent molecular masses of 27, 29, and 30 kDa in HSV-1-infected cells. In this study, we have investigated the intracellular localization and distribution of UL51 protein both in infected cells and in transfected cells expressing only UL51. We found that this protein colocalized closely with Golgi marker proteins such as the Golgi-58K protein and GM130 in transfected cells expressing only UL51. However, in infected cells, the UL51 protein localized to the juxtanuclear region but only partially colocalized with the Golgi maker proteins. Mutant protein analysis revealed that the N-terminal 15 amino acid residues of the UL51 protein sufficed for this Golgi localization property. The UL51 protein redistributed on addition of brefeldin A. This was prevented by pretreatment with 2-deoxyglucose and sodium azide, which results in ATP depletion, but not by pretreatment with NaF and AlCl(3), which activates heterotrimeric G proteins. Moreover, we found that palmitoylation of the UL51 protein through the N-terminal cysteine at position 9 was necessary for its Golgi localization. Protease digestion analysis suggested that the UL51 protein localized on the cytoplasmic face of the membrane in UL51-transfected cells, while in infected cells it localized mainly to the inside of cytoplasmic vesicles and/or the viral envelope. Transmission immunoelectron microscopy revealed an association of UL51 protein-specific labeling with cytoplasmic virions and also with some membranous structure. We infer from these observations that internalization of UL51 protein into the cytoplasmic vesicle and/or virion may occur in association with viral envelopment in HSV-infected cells.


title: TAP CBRN preparedness: knowledge, training and networks.

text: The main goal of this targeted agenda program (TAP) was the establishment of an international network that would be able to advise on how to improve education and training for chemical, biological, radiological, or nuclear (CBRN)) responders. By combining the members of the TAP group, the CBRN Task Force of the World Association for Disaster and Emergency Medicine (WADEM) and the European network of the Hesculaep Group, an enthusiastic and determined group has been established to achieve the defined goal. It was acknowledged that the bottlenecks for education and training for CBRN responders are mainly awareness and preparedness. For this reason, even basic education and training on CBRN is lacking. It was advised that the focus for the future should be on the development of internationally standardized protocols and standards. The face-to-face discussions of the TAP will be continued at future Hesculaep expert meetings. The intention is that during the 16WCDEM, the achievements of the established network will be presented.


Intrinsically contaminated alcohol-free mouthwash implicated in a nosocomial outbreak of Burkholderia cepacia colonization and infection.


title: Understanding the super-spreading events of SARS in Singapore.

text: INTRODUCTION It has been noted that SARS transmission is characterised by a few super-spreading events (SSEs) giving rise to a disproportionate number of secondary cases. Clinical and environmental features surrounding the index cases involved were compared with cases in non- SSEs. MATERIALS AND METHODS Data on 231 cases of probable SARS admitted to Tan Tock Seng Hospital (TTSH) were used. Index cases directly causing 10 or more secondary cases were classified as having been involved in SSEs; all others were defined as non-SSEs. RESULTS Only 5 cases were involved in SSEs; all 5 were isolated on day 5 of illness or later, and spent at least a brief period in a non-isolation ward; in contrast, amongst the 226 non-SSE cases, only 40.7% and 4.0% were isolated late and admitted to non-isolation wards respectively, and only 3.1% had both these environmental features present; the differences were highly significant (P = 0.012, P <0.001 and P <0.001 by Fisher's Exact test). When compared to 7 non-SSE cases with delayed isolation and an admission to non-isolation wards, SSEs were more likely to have co-morbid disease or require ICU care at time of isolation (P = 0.045 for both factors). CONCLUSION SSEs were likely due to a conglomeration of environmental factors of delayed isolation and admission to a non-isolation ward, coupled with severe disease stage at time of isolation.


title: Combination of functionalized nanoparticles and polymerase chain reaction-based method for SARS-CoV gene detection.

text: Rapid and sensitive detection of SARS associated coronavirus is critical for early diagnosis and control of severe acute respiratory syndrome. This study describes a method for the detection of SARS associated coronavirus gene by the combination of functionalized nanoparticles and PCR-based assay. In this method, the target cDNA of SARS associated coronavirus was firstly captured and enriched from the mixture of target cDNA and non-target cDNA by the use of the functionalized silica coated superparamagnetic nanoparticles. Additionally, the enriched target cDNA were amplified through a general symmetry PCR and then was selectively isolated from the double strands PCR products by applying the silica coated superparamagnetic nanoparticles again. Finally, we detected the amplified target cDNA by employing the functionalized silica coated fluorescent nanoparticles as signaling probes with a sandwich hybridization format. The results show that the target cDNA can be assayed successfully with a detection limit of 2.0 x 10(3) copies and the nonspecific amplification could be inhibited. In addition, the detection procedure is rapid and can be completed in less than 6 h. Our results suggest that this approach will provide promising prospects for other pathogens detection.


Monoclonal antibodies to two bovine coronavirus glycoproteins neutralize virus infectivity.


title: Cleavage between replicase proteins p28 and p65 of mouse hepatitis virus is not required for virus replication.

text: The p28 and p65 proteins of mouse hepatitis virus (MHV) are the most amino-terminal protein domains of the replicase polyprotein. Cleavage between p28 and p65 has been shown to occur in vitro at cleavage site 1 (CS1), (247)Gly downward arrow Val(248), in the polyprotein. Although critical residues for CS1 cleavage have been mapped in vitro, the requirements for cleavage have not been studied in infected cells. To define the determinants of CS1 cleavage and the role of processing at this site during MHV replication, mutations and deletions were engineered in the replicase polyprotein at CS1. Mutations predicted to allow cleavage at CS1 yielded viable virus that grew to wild-type MHV titers and showed normal expression and processing of p28 and p65. Mutant viruses containing predicted noncleaving mutations or a CS1 deletion were also viable but demonstrated delayed growth kinetics, reduced peak titers, decreased RNA synthesis, and small plaques compared to wild-type controls. No p28 or p65 was detected in cells infected with predicted noncleaving CS1 mutants or the CS1 deletion mutant; however, a new protein of 93 kDa was detected. All introduced mutations and the deletion were retained during repeated virus passages in culture, and no phenotypic reversion was observed. The results of this study demonstrate that cleavage between p28 and p65 at CS1 is not required for MHV replication. However, proteolytic separation of p28 from p65 is necessary for optimal RNA synthesis and virus growth, suggesting important roles for these proteins in the formation or function of viral replication complexes.


title: The role of the intensive care unit environment in the pathogenesis and prevention of ventilator-associated pneumonia.

text: Ventilator-associated pneumonia is preceded by lower-respiratory-tract colonization by pathogenic microorganisms that derive from endogenous or exogenous sources. Most ventilator-associated pneumonias are the result of exogenous nosocomial colonization, especially, pneumonias caused by resistant bacteria, such as methicillin-resistant Staphylococcus aureus and multi-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, or by Legionella species or filamentous fungi, such as Aspergillus. Exogenous colonization originates from a very wide variety of animate and inanimate sources in the intensive care unit environment. As a result, a strategic approach that combines measures to prevent cross-colonization with those that focus on oral hygiene and prevention of microaspiration of colonized oropharyngeal secretions should bring the greatest reduction in the risk of ventilator-associated pneumonia. This review examines strategies to prevent transmission of environmental pathogens to the vulnerable mechanically-ventilated patient.


title: Synergism of the 3'-untranslated region and an internal ribosome entry site differentially enhances the translation of a plant virus coat protein.

text: The use of internal ribosome entry sites (IRESs) is one of the unorthodox mechanisms exploited by viruses to initiate the translation of internal genes. Herein, we report a plant virus exploiting an IRES and its 3'-untranslated region (UTR) to express its internal genes, notably the 3'-proximal viral coat protein gene. Hibiscus chlorotic ringspot virus (HCRSV), a positive-strand non-polyadenylated RNA virus, was demonstrated to harbor a unique 100-nucleotide (nt) IRES, located 124 nt upstream of the coat protein gene, that could function in wheat germ extract, rabbit reticulocyte lysate, and mammalian cells. In comparison with other known IRESs of picornaviruses and eukaryotic mRNAs, this 100-nt IRES is distinctively short and simple. The IRES activity was tested in homologous and heterologous bicistronic constructs, and the expression of the 3'-proximal gene was enhanced when the 3'-UTR was present. When the IRES element was bisected, each half still possessed IRES activity and could initiate internal translation on its own. Site-directed mutagenesis and deletion analyses revealed that the primary sequence within the 5' half was crucial for IRES activity, whereas the primary sequence of the second half and a GNRA motif were non-essential. To our knowledge, this is the first report describing a mechanism whereby an IRES, located in the 3' portion of the virus genome, co-operates with the 3'-UTR to enhance gene expression differentially.


title: Coronavirus-like particles in Aboriginals and non-Aboriginals in Western Australia.

text: Pleomorphic virus-like particles which resemble coronaviruses in morphology were found in faecal specimens from Aboriginal and non-Aboriginal children in Western Australia. They were equally prevalent in those with or without symptoms of diarrhoea. A much greater proportion of Aboriginal than non-Aboriginal children were found to be excreting the particles. The proportion of children who excreted the virus-like particles increased with age. Coronavirus-like particles, indistinguishable from those found in humans, were found in a number of Aboriginals' dogs.


title: Control of Extensively Drug-Resistant Tuberculosis (XDR-TB): A Root Cause Analysis.

text: The threat of global infectious agents has the potential to cripple national and global economies, as the outbreaks of SARS, Avian Flu, H1N1, and XDR-TB have demonstrated. This article offers a Root Cause Analysis (RCA) of one public health case study - the Speaker case of XDR-TB - pinpointing the underlying causal relationships associated with this global health incident and proposing recommendations for preventing its recurrence. An RCA approach identifies corrective actions directed at the root causes of the problem and advances them as necessary to eliminate global contagion with its major international public health risks. To my knowledge, this is the first root cause analysis of a global health problem. The reform this article proposes would be to add a standardized procedure akin to the informed consent process in clinical ethics, but within a shared health governance framework. This approach, addressing infectious agents at their origins or source, is potentially a more effective strategy to reduce uncertainty and avert global health threats.


title: [A clinicopathological study on 3 cases of severe acute respiratory syndrome].

text: OBJECTIVE To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation. METHODS Tissue specimens from 3 autopsy cases of diagnosed SARS were studied under microscopy and the clinical data were reviewed. RESULTS The typical pathological changes of lungs were diffuse hemorrhage on surface. A mixture features of serous, fibrinous and hemorrhagic inflammation were seen in most pulmonary alveoli with engorgement of capillary and there were microthrombosis in some capillary. Pulmonary alveoli became thick with interstitial mononuclear inflammatory infiltration, diffused alveoli damage, desquamation of pneumocytes and hyaline-membrane formation. Fibrinoid materials and erythrocytes could be found in alveolar spaces. There were thrombo-embolisms in some bronchial artery. Meanwhile, haemorrhagic necrosis was showed in lymph nodes and spleen with attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and some lesions observed in liver, heart, kidney, pancreas may have existed before the hospitalization. CONCLUSION Severe damages of pulmonary and immunological system damage are responsible for clinical features of SARS and may lead to death of patients.


title: Functional differences in the peplomer glycoproteins of feline coronavirus isolates.

text: The feline coronaviruses can be divided into two distinct antigenic groups on the basis of antigenic differences found on the peplomer (E2) glycoprotein of the virus. Because the E2 glycoprotein is responsible for many of the biological functions of coronaviruses, experiments were done to determine whether there were any E2 functional differences between these two antigenic groups. The avirulent feline infectious peritonitis virus (FIPV) isolate FIPV-UCD-2, which has one antigenic type of E2, was less rapidly internalized and could not spread from cell to cell in the presence of neutralizing antibody. Two virulent isolates, FIPV-DF2 and FIPV-79-1146, as well as the non-FIP-causing feline enteric coronavirus (FECV) isolate FECV-79-1683, all of which have the second antigenic type of E2, were very rapidly internalized and were able to spread from cell to cell despite the presence of neutralizing antibody. The avirulent FIPV-UCD-2 and FECV-79-1683 isolates were more labile at 37 degrees C at pHs of 6.5 and above than were the virulent FIPV-DF2 and FIPV-79-1146 isolates.


title: [Covid-19 in patients on dialysis: infection prevention and control strategies].

text: Covid-19 is a disease caused by a new coronavirus presenting a variability of flu-like symptoms including fever, cough, myalgia and fatigue; in severe cases, patients develop pneumonia, acute respiratory distress syndrome, sepsis and septic shock, that can result in their death. This infection, which was declared a global epidemic by the World Health Organization, is particularly dangerous for dialysis patients, as they are frail and more vulnerable to infections due to the overlap of multiple pathologies. In patients with full-blown symptoms, there is a renal impairment of various degrees in 100% of the subjects observed. However, as Covid-19 is an emerging disease, more work is needed to improve prevention, diagnosis and treatment strategies. It is essential to avoid nosocomial spread; in order to control and reduce the rate of infections it is necessary to strengthen the management of medical and nursing personnel through the early diagnosis, isolation and treatment of patients undergoing dialysis treatment. We cover here a series of recommendations for the treatment of dialysis patients who are negative to the virus, and of those who are suspected or confirmed positive.


title: Porcine reproductive and respiratory syndrome virus-infected alveolar macrophages contain no detectable levels of viral proteins in their plasma membrane and are protected against antibody-dependent, complement-mediated cell lysis.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) can evade the host immune system, which results in prolonged virus replication for several weeks to several months. To date, the mechanisms of PRRSV immune evasion have not been investigated in detail. One possible immune-evasion strategy is to avoid incorporation of viral proteins into the plasma membrane of infected cells, as this prevents recognition by virus-specific antibodies and consequent cell lysis either by the classical complement pathway or by antibody-dependent, cell-mediated cytotoxicity. In this study, viral proteins were not observed in the plasma membrane of in vitro-infected macrophages by using confocal microscopy or flow cytometry. Subsequently, the sensitivity of PRRSV-infected macrophages towards antibody-dependent, complement-mediated cell lysis (ADCML) was determined by using an ADCML assay. A non-significant percentage of PRRSV-infected cells were killed in the assay, showing that in vitro PRRSV-infected macrophages are protected against ADCML. PRRSV proteins were not detected in the plasma membrane of in vivo-infected alveolar macrophages and ADCML was also not observed. Together, these data indicate that viral proteins are not incorporated into the plasma membrane of PRRSV-infected macrophages, which makes infected cells invisible to PRRSV-specific antibodies. This absence of viral proteins on the cell surface could explain the protection against ADCML observed for in vitro and in vivo PRRSV-infected macrophages, and may play a role in virus persistence.


title: CrFK feline kidney cells produce an RD114-like endogenous virus that can package murine leukemia virus-based vectors.

text: The feline kidney cell line CrFK is used extensively for viral infectivity assays and for study of the biology of various retroviruses and derived vectors. We demonstrate the production of an endogenous, RD114-like, infectious retrovirus from CrFK cells. This virus also is shown to efficiently package Moloney murine leukemia virus vectors.


title: Mutational analysis of the active centre of coronavirus 3C-like proteases.

text: Formation of the coronavirus replication-transcription complex involves the synthesis of large polyprotein precursors that are extensively processed by virus-encoded cysteine proteases. In this study, the coding sequence of the feline infectious peritonitis virus (FIPV) main protease, 3CL(pro), was determined. Comparative sequence analyses revealed that FIPV 3CL(pro) and other coronavirus main proteases are related most closely to the 3C-like proteases of potyviruses. The predicted active centre of the coronavirus enzymes has accepted unique replacements that were probed by extensive mutational analysis. The wild-type FIPV 3CL(pro) domain and 25 mutants were expressed in Escherichia coli and tested for proteolytic activity in a peptide-based assay. The data strongly suggest that, first, the FIPV 3CL(pro) catalytic system employs His(41) and Cys(144) as the principal catalytic residues. Second, the amino acids Tyr(160) and His(162), which are part of the conserved sequence signature Tyr(160)-Met(161)-His(162) and are believed to be involved in substrate recognition, were found to be indispensable for proteolytic activity. Third, replacements of Gly(83) and Asn(64), which were candidates to occupy the position spatially equivalent to that of the catalytic Asp residue of chymotrypsin-like proteases, resulted in proteolytically active proteins. Surprisingly, some of the Asn(64) mutants even exhibited strongly increased activities. Similar results were obtained for human coronavirus (HCoV) 3CL(pro) mutants in which the equivalent Asn residue (HCoV 3CL(pro) Asn(64)) was substituted. These data lead us to conclude that both the catalytic systems and substrate-binding pockets of coronavirus main proteases differ from those of other RNA virus 3C and 3C-like proteases.


Imaging Findings in Four COVID-19 Patients.


title: Needle-free vaccine delivery.

text: The need for minimally invasive delivery methods is urgent. As the number of registered vaccines increases, so does the number of injections. The use of sharps can be unsafe and needle immunisation is less suitable for mass immunisations during emergencies such as pandemics or bioterrorist attacks. The approach of combining vaccines has limitations due to high development costs, risk of pharmaceutical or immunological interference and economic risks. Advancements in the development of alternatives to injection with syringes and needles are discussed in this paper, and include: mucosal vaccination, injection without needles and vaccine delivery via the skin.


title: The common cold, pattern sensitivity and contrast sensitivity.

text: Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.


title: Inner structures of some coronaviruses.

text: When treated with formaldehyde, Tween 80, sodium oleate and Nonidet P-40, avian infectious bronchitis virus, porcine transmissible gastroenteritis virus, neonatal calf diarrhea coronavirus, porcine hemagglutinating encephalomyelitis virus as well as the human coronavirus show similar inner structures by negative staining. The first one is an inner membranous bag. This structure could be evaginated following treatments used and does not show the characteristic projections of coronaviruses. Subsequently, the inner fold could be separated from the outer membrane at the point of junction between these two membranes. Each virus does not react in the same way to the action of the different products. The transmissible gastroenteritis virus appears more sensitive to treatments than other viruses. On the other hand, the hemagglutinating encephalomyelitis virus is the most resistant. The variable sensitivities of these viruses are not related to the type of host-cells. Also, a second internal structure, which is more dense than the viral particle, encircles partially the aperture of the internal tongue-shaped structure and seems to emerge from the viral particle through the aperture of the inner bag.


title: [Optimal stroke prevention in the geriatric patient with atrial fibrillation: position paper of an interdisciplinary expert panel].

text: BACKGROUND The optimal approach to stroke prevention in geriatric patients with atrial fibrillation (AF) has not been adequately clarified. Despite their high risk of stroke and clear indication for anticoagulation according to established risk scores, in practice geriatric AF patients often are withheld treatment because of comorbidities and comedications, concerns about low treatment adherence or fear of bleeding events, in particular due to falls. METHOD The present position paper summarises the outcomes of an expert panel discussion held by hospital-based and office-based physicians with ample experience in the treatment of geriatric patients. RESULTS AND CONCLUSIONS The panel agreed that geriatric patients should receive oral anticoagulation as a rule, unless a comprehensive neurological and geriatric assessment (including clinical examination, gait tests and validated instruments such as Modified Rankin Scale, Mini-mental state examination or Timed Test of Money Counting) provides sound reasons for refraining from treatment AII patients with a history of falls should be thoroughly evaluated for further evaluation of the causes. Patients with CHADS2 score ≥ 2 should receive anticoagulation even if at high risk for falls. The novel oral anticoagulants (NOAC) facilitate management in the geriatric population with AF (no INR monitoring needed, easier bridging during interventions) and have an improved benefit-risk ratio compared to vitamin K antagonists. Drugs with predominantly non-renal elimination are safer in geriatric


title: [Detection of SARS-CoV RNA in stool samples of SARS patients by nest RT-PCR and its clinical value].

text: OBJECTIVE To investigate of severe acute respiratory syndrome (SARS) convalescent stool shedding by RT-PCR. METHODS One hundred and three stool samples from 46 SARS patients were collected on May 16th, 20th, and 23rd, 2003. For each sample, RNA was extracted using commercial kit and 7 Nest RT-PCR using a 14-pair different SARS-associated coronavirus (SARS-CoV) special primers were carried out simultaneously. RESULTS Among these 46 SARS patients, 17 cases (37.0%) were stool SARS-CoV RT-PCR negative, and 29 cases (63.0%) were SARS-CoV RT-PCR positive. The duration of positive cases lasted (31.76 +/- 10.78) d (12-64 d). The longest stool shedding case in this study lasted 64 days. Two serial stool samples and for each sample 2 RT-PCR tests using different primers were positive in this case. CONCLUSIONS Our study observed longest stool shedding of SARS patients to be 64 days after initial onset of SARS. The average stool shedding was 32 days. Hence it is important to think highly of SARS convalescent patient stool sterilization.


title: Characterization of the RNA components of a putative molecular switch in the 3' untranslated region of the murine coronavirus genome.

text: RNA virus genomes contain cis-acting sequence and structural elements that participate in viral replication. We previously identified a bulged stem-loop secondary structure at the upstream end of the 3' untranslated region (3' UTR) of the genome of the coronavirus mouse hepatitis virus (MHV). This element, beginning immediately downstream of the nucleocapsid gene stop codon, was shown to be essential for virus replication. Other investigators discovered an adjacent downstream pseudoknot in the 3' UTR of the closely related bovine coronavirus (BCoV). This pseudoknot was also shown to be essential for replication, and it has a conserved counterpart in every group 1 and group 2 coronavirus. In MHV and BCoV, the bulged stem-loop and pseudoknot are, in part, mutually exclusive, because of the overlap of the last segment of the stem-loop and stem 1 of the pseudoknot. This led us to hypothesize that they form a molecular switch, possibly regulating a transition occurring during viral RNA synthesis. We have now performed an extensive genetic analysis of the two components of this proposed switch. Our results define essential and nonessential components of these structures and establish the limits to which essential parts of each element can be destabilized prior to loss of function. Most notably, we have confirmed the interrelationship of the two putative switch elements. Additionally, we have identified a pseudoknot loop insertion mutation that appears to point to a genetic interaction between the pseudoknot and a distant region of the genome.


title: Diagnosis of acute non-bacterial gastroenteritis by rotavirus detection and serology.

text: In 127 infants and young children suffering from acute non-bacterial gastroenteritis, diagnosis of rotavirus infection was done by virus detection and serology. Human rotavirus (HRV) detection was performed by direct electron microscopy (EM), conventional immune electron microscopy (IEM) and/or solid phase immune electron microscopy ( SPIEM ); rotavirus antigens were detected by indirect double-antibody sandwich (DAS) ELISA and HRV isolation was attempted in MA-104 or LLC-MK2 cell cultures. HRV serology was done on paired sera from all the patients by the indirect immunoperoxidase antibody (IPA) technique for HRV IgG determination, and by an indirect ELISA method using a purified HRV Wa strain as a solid phase. HRV particles were detected by EM and/or IEM in 53 cases (41.7%) and by SPIEM in 5 additional cases; HRV antigens were demonstrated by indirect DAS ELISA in the same 53 cases, whereas 40 cases (31.4%) were positive for HRV isolation in cell cultures. Sixty-four patients (50.3%) seroconverted by IPA and ELISA, including all the cases (58) positive for rotavirus detection in stools and 6 additional cases. Thus, SPIEM appears to be the most sensitive technique for detecting a few virus particles in stool specimens, but HRV serology is the most sensitive method for diagnosing HRV infections retrospectively, when paired sera are drawn at an appropriate time. However, EM possess the great advantage of detecting in fecal specimens viral agents other than rotaviruses, such as adenoviruses, enteric coronaviruses, small round viruses, astroviruses and others.


Pursuing excellence in neurosurgical innovation.


A serologic investigation for coronavirus and Breda virus antibody in winter dysentery of dairy cattle in the northeastern United States.


title: Listeric meningoencephalomyelitis in a cougar (Felis concolor): characterization by histopathologic, immunohistochemical, and molecular methods.

text: Listeria monocytogenes has been recognized as an important food-borne pathogen in animals. Records of the disease caused by this bacterium in large felids are, however, rare. The nervous form of listeriosis was diagnosed in a 12-year-old male cougar (Felis concolor) with a several-day history of neurologic disease characterized by excess salivation, head pressing, and circling that progressed to recumbency and death. Microscopically, the main alteration in the brain and spinal cord was a variably severe meningoencephalomyelitis composed mainly of mononuclear cell aggregates with fewer neutrophils. L. monocytogenes was isolated from the brain by microbiological culture, and L. monocytogenes antigen was detected in formalin-fixed, paraffin-embedded sections of brain and spinal cord by immunohistochemical analysis. On the basis of the nucleotide sequence of the 16S rRNA gene, the isolated strain was determined to be serotype 1/2a. Food-borne transmission of the bacterium was suspected, but food was not available for testing.


title: Essential veterinary education in the cultural, political and biological complexities of international trade in animals and animal products.

text: Globalisation has changed the veterinary profession in many ways and academic institutes may need to re-tool to help future professionals deal with the changes in a successful and productive way. The remarkably expanded and expanding volume of trade and traffic in animals and animal products means that to be effective veterinarians must grasp some of the complexities inherent in this trade. Being able to engage productively in cross-cultural dialogue will be important in negotiations over livestock shipments and also within the context of the delivery of medical services to companion animals in societies that are becoming increasingly diverse. Understanding the political landscapes that influence trade decisions will help to expedite agreements and facilitate the transfer of goods and materials that involve animal health. Disease emergence will continue to occur, and an awareness of the factors responsible and the response measures to undertake will help to contain any damage.


title: Alpha2,6-linked sialic acid acts as a receptor for Feline calicivirus.

text: Feline calicivirus (FCV) is a major causative agent of respiratory disease in cats. It is also one of the few cultivatable members of the family Caliciviridae. It has recently been reported that FCV binding is in part due to interaction with junction adhesion molecule-A. This report describes the characterization of additional receptor components for FCV. Chemical treatment of cells with sodium periodate showed that FCV recognized carbohydrate moieties on the surface of permissive cells. Enzymic treatment with Vibrio cholerae neuraminidase demonstrated that sialic acid was a major determinant of virus binding. Further characterization using linkage-specific lectins from Maackia amurensis and Sambucus nigra revealed that FCV recognized sialic acid with an alpha2,6 linkage. Using various proteases and metabolic inhibitors, it was shown that alpha2,6-linked sialic acid recognized by FCV is present on an N-linked glycoprotein.


title: Molecular characterization of the 229E strain of human coronavirus.

text: Human coronaviruses (HCV) cause various respiratory, gastrointestinal and possibly neurological disorders. Very little is known of the molecular biology of these ubiquitous pathogens. We have undertaken the molecular characterization of the prototype 229E strain of HCV. The virus grew to the highest titers on a human embryonic lung cell line (L132) at 33 degrees C and purification was optimal on Renografin-60 gradients. Metabolic labeling with [35S]methionine or [3H]glucosamine or galactose and analysis by SDS-PAGE revealed at least five structural proteins, which could be identified by analogy with murine coronaviruses as follows: the spike glycoprotein (E2/S), in both monomeric (88-97 kDa) and dimeric (190-200) forms, the nucleoprotein (N) at 52-53 kDa and the matrix protein (E1/M), in both glycosylated (25-26 kDa) and non-glycosylated (20-22 kDa) forms. Monomeric, dimeric and multimeric (greater than 200 kDa) forms of E2/S incorporated glucosamine and galactose, whereas only galactose was incorporated into E1/M. Multimers of E1/M, with apparent molecular masses of 44, 74 and 140 kDa, were formed in the absence of a reducing agent.


Mechanical Small Bowel Obstruction Caused by a Retained Free Intraperitoneal Staple Following Laparoscopic Appendectomy.


title: Modelling the transmission of airborne infections in enclosed spaces.

text: The Wells-Riley equation for modelling airborne infection in indoor environments is incorporated into an SEIR epidemic model with a short incubation period to simulate the transmission dynamics of airborne infectious diseases in ventilated rooms. The model enables the effect of environmental factors such as the ventilation rate and the room occupancy to be examined, and allows the long-term impact of infection control measures to be assessed. A theoretical parametric study is carried out to demonstrate how changes to both the physical environment and infection control procedures may potentially limit the spread of short-incubation-period airborne infections in indoor environments such as hospitals.


title: Characterization of replicative intermediate RNA of mouse hepatitis virus: presence of leader RNA sequences on nascent chains.

text: Mouse hepatitis virus A59 codes for seven mRNAs in infected cells. These mRNAs are transcribed from a minus (-) strand template of genome length and contain a leader RNA at their 5' ends. To further elucidate the mechanism of coronavirus transcription, we examined the structure of mouse hepatitis virus replicative intermediates (RIs) isolated by 2 M NaCl precipitation and Sepharose 2-B column chromatography. Purified RIs migrated as a single species on agarose gels and sedimented between 12 and 38S on 10 to 25% sucrose gradients. The complexes were readily heat denatured into a heterogeneous population of smaller RNA molecules which probably represent nascent plus (+) strands. RNase A digestion of RIs produced a single replicative form which sedimented between 30 and 32S. These data suggest that the RI is composed of a single genome-sized (-) strand hydrogen bonded to an average of 4 to 6.5 nascent (+) strands. In contrast, a column-purified replicative form was extremely resistant to RNase A digestion and heat denaturation and migrated as a single RNA species on agarose gels and sucrose gradients. Oligonucleotide fingerprinting of an RI revealed the presence of the 5' leader RNA on the nascent (+) strands. In addition, an average of 6.2 cap structures were present in each RI, which agrees with the average number of nascent (+) strands per RI. These data suggest that the leader RNA is utilized as a primer for mouse hepatitis virus RNA transcription and is not added to mRNA post-transcriptionally.


title: Viral ecology and the maintenance of novel host use.

text: Viruses can occasionally emerge by infecting new host species. However, the early phases of emergence can hinge upon ecological sustainability of the virus population, which is a product of both within-host population growth and between-host transmission. Insufficient growth or transmission can force virus extinction before the latter phases of emergence, where genetic adaptations that improve host use may occur. We examined the early phase of emergence by studying the population dynamics of RNA phages in replicated laboratory environments containing native and novel host bacteria. To predict the breadth of transmission rates allowing viral persistence on each species, we developed a simple model based on in vitro data for phage growth rate over a range of initial population densities on both hosts. Validation of these predictions using serial passage experiments revealed a range of transmission rates for which the native host was a source and the novel host was a sink. In this critical range of transmission rates, periodic exposure to the native host was sufficient for the maintenance of the viral population on the novel host. We argue that this effect should facilitate adaptation by the virus to utilize the novel host--often crucial in subsequent phases of emergence.


title: Pilot study comparing total intravenous anesthesia to inhalational anesthesia in endoscopic sinus surgery: novel approach of blood flow quantification.

text: OBJECTIVES We compared anesthesia with sevoflurane-remifentanil hydrochloride (SR) to total intravenous anesthesia with propofol-remifentanil hydrochloride (PR) in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis in terms of sinonasal mucosal blood flow, the surgical field visualization score, and blood loss. METHODS We performed a double-blinded prospective study at a tertiary care center in 23 adults scheduled to undergo endoscopic sinus surgery for chronic rhinosinusitis. The patients were randomized to receive SR or PR. The sinonasal mucosal blood flow was measured by optical rhinometry. The surgical field visualization score was based on the Boezaart scale. RESULTS The groups had similar clinical characteristics. During the 60- to 90-minute and 90- to 120-minute operative time windows, the blood flow was significantly greater in the PR group than in the SR group (p = 0.04 and p = 0.03, respectively). The amounts of blood loss in the PR and SR groups were 152.9 +/- 161.3 mL and 355.9 +/- 393.4 mL, respectively (p = 0.12). The median ratios of the surgical field visualization score to the number of sinuses operated on in the PR and SR groups were 2.1 and 1.8, respectively (p = 0.52). CONCLUSIONS The intraoperative blood flow, as determined by optical rhinometry, was significantly greater with anesthesia with PR than with anesthesia with SR, 1 hour into the procedure; however, this difference did not translate into differences in the amounts of operative blood loss or in the surgical field visualization scores.


title: In vivo titration of white spot syndrome virus (WSSV) in specific pathogen-free Litopenaeus vannamei by intramuscular and oral routes.

text: White spot syndrome virus (WSSV) is a devastating pathogen in shrimp aquaculture. Standardized challenge procedures using a known amount of infectious virus would assist in evaluating strategies to reduce its impact. In this study, the shrimp infectious dose 50% endpoint (SID50 ml(-1)) of a Thai isolate of WSSV was determined by intramuscular inoculation (i.m.) in 60 and 135 d old specific pathogen-free (SPF) Litopenaeus vannamei using indirect immunofluorescence (IIF) and 1-step polymerase chain reaction (PCR). Also, the lethal dose 50% endpoint (LD50 ml(-1)) was determined from the proportion of dead shrimp. The median virus infection titers in 60 and 135 d old juveniles were 10(6.8) and 10(6.5) SID50 ml(-1), respectively. These titers were not significantly different (p > or = 0.05). The titration of the WSSV stock by oral intubation in 80 d old juveniles resulted in approximately 10-fold reduction in virus titer compared to i.m. inoculation. This lower titer is probably the result of physical and chemical barriers in the digestive tract of shrimp that hinder WSSV infectivity. The titers determined by infection were identical to the titers determined by mortality in all experiments using both i.m. and oral routes at 120 h post inoculation (hpi), indicating that every infected shrimp died. The determination of WSSV titers for dilutions administered by i.m. and oral routes constitutes the first step towards the standardization of challenge procedures to evaluate strategies to reduce WSSV infection.


title: Fever, pulmonary haemorrhage, and acute renal failure in a young girl.

text: Leptospirosis is rarely reported in children. It is easily treated with antibiotics but can be fatal if treatment is delayed. A 12-year-old girl was diagnosed with Weil syndrome, a severe form of leptospirosis, 10 days after returning from Mainland China. She presented with fever, hypotension, jaundice, and acute renal failure. She had used well water for bathing and swum in freshwater.


title: C-type lectins L-SIGN and DC-SIGN capture and transmit infectious hepatitis C virus pseudotype particles.

text: The molecular mechanisms involved in the hepatic tropism of hepatitis C virus (HCV) have not been identified. We have shown previously that liver-expressed C-type lectins L-SIGN and DC-SIGN bind the HCV E2 glycoprotein with high affinity (Lozach, P. Y., Lortat-Jacob, H., de Lacroix de Lavalette, A., Staropoli, I., Foung, S., Amara, A., Houles, C., Fieschi, F., Schwartz, O., Virelizier, J. L., Arenzana-Seisdedos, F., and Altmeyer, R. (2003) J. Biol. Chem. 278, 20358-20366). To analyze the functional relevance of this interaction, we generated pseudotyped lentivirus particles presenting HCV glycoproteins E1 and E2 at the virion surface (HCV-pp). High mannose N-glycans are present on E1 and, to a lesser extent, on E2 proteins of mature infectious HCV-pp. Such particles bind to both L-SIGN and DC-SIGN, but they cannot use these receptors for entry into cells. However, infectious virus is transmitted efficiently when permissive Huh-7 cells are cocultured with HCV-pp bound to L-SIGN or to DC-SIGN-positive cell lines. HCV-pp transmission via L-SIGN or DC-SIGN is inhibited by characteristic inhibitors such as the calcium chelator EGTA and monoclonal antibodies directed against lectin carbohydrate recognition domains of both lectins. In support of the biological relevance of this phenomenon, dendritic cells expressing endogenous DC-SIGN transmitted HCV-pp with high efficiency in a DC-SIGN-dependent manner. Our results support the hypothesis that C-type lectins such as the liver sinusoidal endothelial cell-expressed L-SIGN could act as a capture receptor for HCV in the liver and transmit infectious virions to neighboring hepatocytes.


title: Lysosomal sorting mutants of coronavirus E1 protein, a Golgi membrane protein.

text: As a model for the intracellular sorting of Golgi membrane proteins, we are studying the E1 protein of the coronavirus Mouse Hepatitis Virus A59. The wild-type protein, when expressed from synthetic RNA, is localised in the Golgi complex. When the second and third of the three predicted membrane-spanning sequences were deleted from the protein, the resulting mutant was retained in the endoplasmic reticulum. In contrast, removal of the first and second membrane-spanning sequences allowed the protein to pass through the Golgi complex and reach the lysosomes. Likewise, when 40 amino acids were deleted from the C-terminal cytoplasmic part of E1, the truncated protein was transported to the lysosomes. We discuss the implications of these results for the structure of the E1 protein and the mechanism by which it is localised in the cell.


title: Differences in the susceptibility of some penaeid prawn species to gill-associated virus (GAV) infection.

text: Four species of penaeid prawn cultured in Australia (Penaeus monodon, Penaeus esculentus, Marsupenaeus japonicus and Fenneropenaeus merguiensis) were injected with a virulent preparation of gill-associated virus (GAV). P. monodon (average weight = 8.9, 13.9 and 19.2 g), P. esculentus (average weight = 19.5 g), F. merguiensis (average weight = 10.5 g), and small (average weight = 5.8 g) M. japonicus displayed overt signs of disease and mortalities which reached 82 to 100% within 23 d post-injection. Cumulative mortalities in P. esculentus and F. merguiensis were significantly lower than for P. monodon of the same size class. Medium (average weight = 13.0 g) M. japonicus also developed overt signs of disease but cumulative mortalities were not significantly higher than uninfected controls. Large (average weight = 20.3 g) M. japoncius did not display symptoms of disease and there were no significant mortalities up to 23 d post-injection.


title: Singapore's experience of SARS.

text: The coronavirus that causes severe acute respiratory syndrome (SARS) is transmitted mainly via respiratory droplets. Typical presenting symptoms are akin to those of ordinary pneumonia. Young patients start with fever, chills, malaise, headache, or myalgia; cough and dyspnoea follow. Older persons and those taking corticosteroids may have neither fever nor respiratory symptoms. Exceptional suspicion is needed to identify SARS early in the illness. During an outbreak, even patients with low suspicion of SARS should be promptly isolated, and all contacts quarantined. Health workers need training in the use of appropriate barriers against droplets and other body fluids. Any fever cluster in patients or carers requires immediate action: discharges, visits, and transfers between wards and hospitals should be stopped. Halting hospital admissions and ten-day quarantine of suspected cases create wide buffer zones. To counter a possible resurgence of SARS, a system of prepared isolation and quarantine facilities is important.


title: Duration of immunity in red wolves (Canis rufus) following vaccination with a modified live parvovirus and canine distemper vaccine.

text: There is growing information available regarding duration of immunity for core vaccines in both domestic and nondomestic species. Vaccination protocols in nondomestic canids have frequently followed guidelines developed for the domestic dog; however, these protocols can be inappropriate for nondomestic canids such as the African wild dog (Lycaon pictus), leaving some animals susceptible to infectious disease and others at risk for contracting vaccine-induced disease. In this study, red wolves (Canis rufus) were vaccinated against canine distemper virus (CDV) and canine parvovirus (CPV) and vaccination titers were followed annually for 3 yr. One hundred percent of wolves developed and maintained a positive titer to CDV for 3 yr and 96.9% of wolves developed and maintained a positive titer to CPV for 3 yr. Seroconversion for canine adenovirus was sporadic. The results of this study support decreasing the frequency of vaccine administration in the red wolf population to a triennial basis.


title: On medical confidentiality (not only) in time of coronavirus.

text: One of the compulsory secret exceptions derives from the situation within which the data about patient must be provided to the third person in the interest of his/her health protection. Despite some interpretation difficulties any providing information according to this legal exception is allowed only on the base of proved and re-examined facts. The state of emergency itself is not the base for the compulsory secret breach.


title: Studies of SARS virus vaccines.

text: 1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.


title: Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period.

text: OBJECTIVE To evaluate thin-section computed tomography findings of patients with severe acute respiratory syndrome (SARS) in the convalescent period and to correlate the results with clinical parameters and lung function tests. METHODS Ninety-nine severe acute respiratory syndrome patients with persistent changes on follow-up chest radiography were included. One hundred seventy computed tomography examinations at baseline (n=70), 3 months (n=56), and 6 months (n=44) were retrospectively evaluated to determine the extent of ground-glass opacification, reticulation, and total parenchymal involvement. Patients' demographic information, clinical information during treatment, and results of lung function tests at 3 and 6 months were correlated with computed tomography findings. RESULTS A significant serial improvement in the extent of overall ground-glass opacification, overall reticulation, and total parenchymal involvement was observed (P <0.01). Advanced age, previous intensive care unit admission, mechanical ventilation, alternative treatment, higher peak lactate dehydrogenase, and peak radiographic involvement during treatment showed a positive correlation with overall reticulation and total parenchymal involvement at 6 months. There was a significant negative correlation between overall reticulation and total parenchymal involvement with diffusion capacity adjusted for hemoglobin at 3 and 6 months (P <0.01). CONCLUSION Lung changes on thin-section computed tomography of severe acute respiratory syndrome patients improved with time during the convalescent period and showed a significant correlation with advanced age, parameters indicating severe illness, and diffusion capacity adjusted for hemoglobin on follow-up.


title: Transanal endoscopic video-assisted (TEVA) resection of early rectal lesions using a SILS port A single center experience.

text: UNLABELLED represents a safe and complete technique to remove benign lesions of the rectum not treatable by endoscopy and malignant rectal lesions at early stage. It is a valid alternative to transanal endoscopic microsurgery (TEM), to conventional transanal surgery and to transabdominal resection. METHODS In our operating Unit we performed a resection of 8 voluminous adenoma in the rectal ampulla with SILSTM-Port. RESULTS The mean age of the patients was of 51.1 years, the mean BMI was 23. There were not intra or post-operative complications nor conversions to conventional transanal excision or major resective surgery. The postoperative course was normal. The average time of hospitalization was 3 days. CONCLUSIONS TEVA is easier to perform than TEM and does not require a long training and specific and expensive material as the TEM does. TEVA might go to replace completely TEM. KEY WORDS Rectal tumours, SILS, TEVA.


title: [Dynamics of T lymphocyte subsets in SARS patients].

text: OBJECTIVE To study dynamics of T lymphocyte subsets in severe acute respiratory syndrome (SARS). METHODS Sequential anti-coagulated blood samples were collected from 46 cases of SARS patients during the 1st week, the 2nd week, the 3rd-5th week and the 8th-12th week after the infection. T lymphocyte subsets including CD3+CD4+ cells, CD3+CD8+ cells, naive CD4+ cells (CD4+CD45RA+CD62L+) and activated CD8+ cells (CD8+CD38+) were detected by 3-color flow cytometry. Fifty-six normal healthy blood donors were also detected as normal controls. RESULTS Compared with the results of normal controls, both of the percentages of CD4+ cells and CD8+ cells of SARS patients were in normal levels during the 1st week, but the cell counts decreased significantly to (306 +/- 140)/mm3 and (270 +/- 143)/mm3, respectively. The cell count of naive CD4+ subset also remarkably decreased to (96 +/- 49)/mm3, and the percentage of CD8+CD38+ subset was higher than that of normal controls [(59.3 +/- 12.6)% vs (44.9 +/- 12.5)%]. During the 3rd-5th week, the CD8+ cell count and the percentage of CD8+CD38+ subset reached normal values, which were (581 +/- 356)/mm3 and (40.1 +/- 17.6)%, respectively. During the 8th-12th week, the cell counts of CD4+ cell [(578 +/- 193)/mm3] and naive CD4+ subset [(176 +/- 64)/mm3] were still less than those of normal controls, while compared with those of the 1st week, the increments were remarkable. CONCLUSIONS T lymphocytes of SARS patients decreased dramatically but could be obviously resumed in a short time. It will take more than 8-12 weeks for CD4+ cell and naive CD4+ subset to reach to normal levels.


title: A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD-positive red blood cell clearance rate with polymorphisms in the FcgammaRIIA and FcgammaIIIA genes.

text: A single recombinant immunoglobulin G1 (IgG1) anti-RhD antibody (MonoRho) was compared with a currently used polyclonal anti-RhD product (Rhophylac) in a phase 1 study for safety, efficacy of Rhesus D (RhD)-positive red blood cell (RBC) clearance, and prevention of RhD immunization in RhD-negative men challenged with 15 mL RhD-positive RBCs. Both the polyclonal product and recombinant anti-RhD effectively cleared RhD-positive RBCs after intravenous and intramuscular injection. The recombinant anti-RhD demonstrated a slower clearance rate compared with the polyclonal anti-RhD. There was no dose response, and there was considerable variation among subjects who received the same dose of recombinant anti-RhD. Interestingly, RhD-positive RBC clearance rates were strongly associated with Fcgamma receptor IIA (FcgammaRIIA) and FcgammaIIIA but not with FcgammaIIIB polymorphisms. Subjects homozygous for FcgammaRIIA-131H or FcgammaRIIIA-158V allotypes showed a faster clearance rate compared with both the heterozygote and the corresponding alternative homozygote allotypes. A similar but less marked trend was seen for the polyclonal anti-RhD. Despite the variation in clearance rates there was no evidence of anti-RhD alloantibodies in any of the subjects at +6 months after the RBC challenge.


title: Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.

text: Despite extensive laboratory investigations in patients with respiratory tract infections, no microbiological cause can be identified in a significant proportion of patients. In the past 3 years, several novel respiratory viruses, including human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and human coronavirus NL63, were discovered. Here we report the discovery of another novel coronavirus, coronavirus HKU1 (CoV-HKU1), from a 71-year-old man with pneumonia who had just returned from Shenzhen, China. Quantitative reverse transcription-PCR showed that the amount of CoV-HKU1 RNA was 8.5 to 9.6 x 10(6) copies per ml in his nasopharyngeal aspirates (NPAs) during the first week of the illness and dropped progressively to undetectable levels in subsequent weeks. He developed increasing serum levels of specific antibodies against the recombinant nucleocapsid protein of CoV-HKU1, with immunoglobulin M (IgM) titers of 1:20, 1:40, and 1:80 and IgG titers of <1:1,000, 1:2,000, and 1:8,000 in the first, second and fourth weeks of the illness, respectively. Isolation of the virus by using various cell lines, mixed neuron-glia culture, and intracerebral inoculation of suckling mice was unsuccessful. The complete genome sequence of CoV-HKU1 is a 29,926-nucleotide, polyadenylated RNA, with G+C content of 32%, the lowest among all known coronaviruses with available genome sequence. Phylogenetic analysis reveals that CoV-HKU1 is a new group 2 coronavirus. Screening of 400 NPAs, negative for SARS-CoV, from patients with respiratory illness during the SARS period identified the presence of CoV-HKU1 RNA in an additional specimen, with a viral load of 1.13 x 10(6) copies per ml, from a 35-year-old woman with pneumonia. Our data support the existence of a novel group 2 coronavirus associated with pneumonia in humans.


title: Acute renal failure in patients with severe acute respiratory syndrome.

text: BACKGROUND AND PURPOSE Severe acute respiratory syndrome (SARS) is caused by a new coronavirus, and results in respiratory failure. Acute renal failure (ARF) may also occur and/or complicate the disease course, however, its incidence, causes and impact in SARS patients are not known. METHODS ARF patients were identified from a total of 78 (33 men and 45 women) probable SARS cases admitted to a single hospital. The clinical features of patients with ARF were characterized, and the etiologies analyzed. RESULTS Patients were assigned to ARF (n = 13; 17%) and non-ARF groups (n = 65). Patients with ARF were older than their non-ARF counterparts. ARF developed 7.2 +/- 4.3 days after admission. The incidence of ARF was higher in males (77% vs 35%; p < 0.05). Comorbidities of diabetes and heart failure were more common in patients who developed ARF (38% vs 6%, p < 0.01 and 38% vs 2%, p < 0.001, respectively) and the incidence of respiratory failure (85% vs 26%, p < 0.001) and mortality (77% vs 8%, p < 0.001) were also higher. Multiple organ system failure usually accompanied ARF. Hypotension (77%) caused by nosocomial infections, gastrointestinal bleeding, or SARS per se, and rhabdomyolysis (43%) was associated with ARF in addition to pre-renal factors. Five patients in the ARF group and 1 female patient with end-stage renal failure underwent renal replacement therapy during hospitalization; however, both eventually died. Of the 16 medical staff performing renal replacement therapy, none was subsequently infected with SARS coronavirus. CONCLUSIONS Development of ARF during the disease course in SARS patients is associated with catastrophic outcome. The cause of ARF in SARS patients is often associated with pre-renal factors, hypotension, rhabdomyolysis, and previous comorbidities including diabetes and old age. Universal precautions to prevent viral transmission are mandatory for medical staff performing renal replacement therapy.


title: [Transanal endoscopic microsurgery (TEM)].

text: Minimally invasive surgery is mandatory for rectal tumors to reduce surgical complications and to improve the quality of life. The conventional transanal procedure is one from of minimally invasive surgery for rectal tumors, but it is still often difficult to reach the middle and upper thirds of the rectum due to anatomical characteristics. Transanal endoscopic microsurgery (TEM) is a technique that allows radical resection of rectal tumors in the distal as well as proximal third of the rectum. Performing radical surgery using this technique requires preoperative estimation of tumor extension both histologically and by X-ray images. It should allow provide safe and radical excision of rectal tumors. In our department, patients with rectal tumors are evaluated for risk factors using barium enema, endoscopic ultrasound, punch biopsy, etc. Fifty patients (rectal cancer, 34: cartinoid, 4: adenoma, 12) have undergone radical TEM. The operation was converted to open surgery in 2 cases because of rectal perforation. Radical open surgery was performed after TEM in 1 patient since cancer invasion was revealed by postoperatively upon histological examination. We conclude that TEM is a useful technique for radical resection of rectal tumors and is associated with a low rate of postoperative complications and a high surgical success rate.


title: Health-promoting behaviors through pregnancy, maternity leave, and return to work: effects of role spillover and other correlates.

text: Women's health-promoting behavior changes and their correlates across the transition to motherhood and return to work are insufficiently understood. The purpose of this study was to describe and compare women's health-promoting behaviors, particularly physical activity (PA), across these transitions. A prospective, observational design was employed to assess 243 female healthcare workers from 3 sites with regard to health-promoting behaviors, and their demographic (e.g., age, parity) and psychosocial (i.e., work-family role spillover) correlates. Forty-two participants were recruited while pregnant and re-assessed during maternity leave and upon return to work, and compared to 201 non-pregnant participants. No significant changes in health-promoting behaviors were observed from pregnancy through the postpartum. Pregnant participants reported better nutrition than comparison participants (p=.001), and were more likely to check their pulse when exercising (p=.004). During pregnancy, health-promoting behaviors were related to parental status, with first-time mothers engaging in more positive behaviors. Correlates of PA during maternity leave and return to work included family income and exercise history. Positive family-to-work spillover was significantly greater among pregnant women than among comparison participants (p<.001), and positive work-to-family spillover was related to greater PA upon return to work (p<.01). This study reveals little variability in health-promoting behaviors from the prenatal to the postpartum period. Both demographic and psychosocial factors have effects on health-promoting behaviors, and we must look to these correlates to promote increased PA.


title: [Collateral damage of COVID-19 pandemic in private healthcare centres of Argentina].

text: To contain the coronavirus pandemic (COVID-19), a strict nationwide lockdown has been enforced and the health systems have been reorganized to deal with this entity. During this period, changes in the care of non-infectious diseases have been observed. Our aim was to describe the impact of the COVID-19 pandemic in the care of non-communicable diseases. A structured retrospective survey was carried out in 31 healthcare centers affiliated with the Asociación de Clínicas, Sanatorios y Hospitales Privados de la República Argentina y Cámara de Entidades de Diagnóstico y Tratamiento. We compared data for April 2019 versus April 2020 regarding emergency room consultations, hospital admissions, invasive procedures and treatments, and bed occupancy. In April 2020, we observed a decrease in emergency room visits (75%) and hospitalizations (48%). A 62% decrease in admissions was noted for angina pectoris and acute coronary syndromes and a 46% decrease in admissions for stroke and transient ischemic attack. A meaningful decrease was found in coronary angioplasties (59%) and total percutaneous interventions (65%), and also a decrease in general surgeries (73%), and cardiac surgeries (58%). Although social distancing measures are a key public health strategy to flatten the infection curve, the observed decrease in medical visits and interventions may impact negatively on cardiovascular, cerebrovascular and cancer related morbidity and mortality. A collective effort is required to avoid the unintended consequences and collateral damage of the COVID-19 pandemic.


title: The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5' to 3' viral helicases.

text: The putative NTPase/helicase protein from severe acute respiratory syndrome coronavirus (SARS-CoV) is postulated to play a number of crucial roles in the viral life cycle, making it an attractive target for anti-SARS therapy. We have cloned, expressed, and purified this protein as an N-terminal hexahistidine fusion in Escherichia coli and have characterized its helicase and NTPase activities. The enzyme unwinds double-stranded DNA, dependent on the presence of a 5' single-stranded overhang, indicating a 5'o 3' polarity of activity, a distinct characteristic of coronaviridae helicases. We provide the first quantitative analysis of the polynucleic acid binding and NTPase activities of a Nidovirus helicase, using a high throughput phosphate release assay that will be readily adaptable to the future testing of helicase inhibitors. All eight common NTPs and dNTPs were hydrolyzed by the SARS helicase in a magnesium-dependent reaction, stimulated by the presence of either single-stranded DNA or RNA. The enzyme exhibited a preference for ATP, dATP, and dCTP over the other NTP/dNTP substrates. Homopolynucleotides significantly stimulated the ATPase activity (15-25-fold) with the notable exception of poly(G) and poly(dG), which were non-stimulatory. We found a large variation in the apparent strength of binding of different homopolynucleotides, with dT24 binding over 10 times more strongly than dA24 as observed by the apparent Km.


title: Effect of maximizing oxygen delivery on morbidity and mortality rates in critically ill patients: a prospective, randomized, controlled study.

text: OBJECTIVE To determine the effects of optimizing oxygen delivery (DO2) to "supranormal" levels on morbidity and mortality in patients with sepsis, septic shock, and adult respiratory distress syndrome. DESIGN A prospective, randomized, controlled trial. SETTING A 16-bed surgical intensive care unit (ICU) and 14-bed mixed medical/surgical ICU in two separate hospitals in the University of Hawaii Surgical and Internal Medicine Residency programs. PATIENTS During a 1-yr period, 67 patients who had pulmonary artery catheters and who met the criteria for sepsis or septic shock, adult respiratory distress syndrome, or hypovolemic shock were enrolled in the study. Patients admitted to the ICU who were < 18 yrs old, or with a do-not-resuscitate order, or those patients who faced imminent death (< 24 hrs), such as those patients with uncontrollable hemorrhage or brain death, were excluded from the study. INTERVENTIONS Patients were randomized into treatment and control groups. The treatment group was assigned a therapeutic DO2 indexed (DO2I) goal of > 600 mL/min/m2. Interventions to attain this goal included fluid boluses, administration of blood products, and the use of inotropes. The control group was not assigned to a specific therapeutic goal other than "normal" values of DO2I of 450 to 550 mL/min/m2. Every attempt was made to reach the therapeutic goals within the first 24 hrs after entry into the study. Hemodynamic measurements were obtained on study patients every 4 hrs until the end of the study. The severity of illness was evaluated using the Therapeutic Intervention Scoring System, and the Acute Physiology and Chronic Health Evaluation II scoring system. MEASUREMENTS AND MAIN RESULTS There were 32 patients in the control group and 35 patients in the treatment group. The groups were similar in age, sex, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention scores. There were no statistical differences between the two groups in mortality, development of organ failure, ICU days, and hospital days. Upon analysis, it became apparent that the patients comprised clinically distinct subgroups, including: a) a treatment group who achieved supranormal DO2I; b) a control group with normal DO2I; c) a treatment group who failed to reach target DO2I; d) a control group who self-generated to high DO2I values; and e) a small number of patients who could not even reach a normal DO2I of 450 mL/min/m2. These subgroups were found to be similar and matched. The mortality rate was significantly lower for patients in groups who reached supranormal values of DO2I whether treated or self-generated as compared with patients who reached normal DO2I values (14% vs. 56%, p = .01). CONCLUSIONS Although there was no statistically significant difference in the control vs. treatment groups, subgroup analysis demonstrated a strong, significant difference between patients with supranormal values of oxygen transport vs. patients with normal levels of DO2. Supranormal values of DO2I, whether self-generated or as a result of treatment, resulted in a statistically significant decrease in mortality rate. This study adds to the weight of evidence that current standard of care of treating critically ill patients to normal DO2I should be reconsidered, and that maximizing to high DO2I might be a more appropriate therapeutic end-point.


title: An adenovirus recombinant expressing the spike glycoprotein of porcine respiratory coronavirus is immunogenic in swine.

text: The full-length spike (S) gene of porcine respiratory coronavirus (PRCV) was inserted into the genome of human adenovirus type 5 downstream of the early transcription region 3 promoter. The recombinant virus replicated in cultures of the swine testicle ST cell line and directed the synthesis of S antigen with a maximum yield of approximately 26 micrograms per 10(6) cells. The antigen was cell-associated except in the late phase of the infection, when a small amount (3.5 micrograms per 10(6) cells) was released. The cell-associated antigen consisted of polypeptides of molecular mass 160 kDa and 175 kDa, comigrating with the authentic precursor S' and the mature S protein of PRCV, respectively. The extracellular recombinant antigen corresponded to the 175 kDa mature protein. Some recombinant S protein was exposed on the cell surface and was recognized by neutralization-mediating anti-S monoclonal antibodies. Piglets, inoculated oronasally with the recombinant adenovirus vector developed PRCV-neutralizing serum antibodies and were partially protected against PRCV challenge, demonstrating the potential of live adenovirus as vaccine vector.


title: Studies of respiratory disease in random-source laboratory dogs: viral infections in unconditioned dogs.

text: A prospective study was conducted to identify the viruses causing respiratory diseases in unconditioned, random-source dogs. During the quarantine period, respiratory disease occurred in 86 of 167 (52%) dogs, and 34 (21%) died. Most affected dogs had a distemper-like illness which required extensive and prolonged care. Histopathologic studies confirmed the diagnosis of canine distemper in 10 of 12 (83%) fatal infections examined. Sixty-seven of 91 (74%) dogs which arrived without canine distemper antibody became ill, and 30 (32%) died. In contrast, only 16 of 67 (24%) dogs with canine distemper antibody had respiratory disease, and only 3 (4%) died. Parainfluenza SV5 and canine adenovirus--type II were recovered from 27 of 54 and 22 of 54 sick dogs, respectively. Canine herpesviruses, canine coronaviruses, and canine parvoviruses were less frequently isolated. Increased antibody titers to SV5 were found consistently, and rises in titer to the other viruses were demonstrated. Many of the sick dogs were infected with two or more viruses. Although several viral agents were detected during these epizootics, prevention of canine distemper appeared to be the key to controlling severe, prolonged, and often fatal respiratory disease.


title: Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS).

text: BACKGROUND A study was undertaken to investigate the aerobic capacity and pulmonary function of children 6 and 15 months after the diagnosis of severe acute respiratory syndrome (SARS). METHODS Thirty four patients of mean age 14.7 years completed both pulmonary function and maximal aerobic capacity tests at 6 months. All had normal clinical examination and were asymptomatic. Their exercise responses were compared with a group of healthy controls. Complete data were collected on 27 of the original 34 cases at 15 months. RESULTS Compared with normal controls, the patient group had significantly lower absolute and mass related peak oxygen consumption (peak V o(2) (p<0.01)), higher ventilatory equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and out of proportion with the degree of lung function abnormality. Residual high resolution computed tomography of thorax (HRCT) abnormalities were present in 14 patients. Those with abnormal HRCT findings had significantly lower mass related peak V o(2) than subjects with normal radiology (p<0.01). Absolute and mass related peak V o(2) in the patient group remained impaired at 15 months despite normalisation of lung function in all patients. CONCLUSIONS The mechanism for the reduced aerobic capacity in children following SARS is not fully understood, but it is probably a consequence of impaired perfusion to the lungs at peak exercise and deconditioning.


[DISEASES OF THE NEWBORN].


title: REMEDIAL APPLICATIONS OF EXOSOMES IN CANCER, INFECTIONS AND DIABETES.

text: Different cell types under normal and diseased states constantly secrete numerous membrane vesicles including exosomes into extracellular space wkich can be isolated from various biological fluids and cell culture supernatants. Exosomal diameter ranges between 40-100 nm. In current research, exosomes are being exploited as biomarkers for pathological diagnosis and potential remedy against various disease conditions such as infections and autoimmune disorders. In cancer immunotherapy, exosomes have promisingly been employed due to the identical immunogenic antigens of exosomes produced by neoplastic cells and the originating tissues. Antigen-specific T-cell activation and immunomodulatory activity is observed to be performed by exosomes isolated from tumor and dendritic cells (DCs). However, more research is still required to uncover the realistic uses of exosomes, particularly as drug delivery tool in autoimmune diseases, cancers and diabetes.


Novel Coronavirus Mimicking Kawasaki Disease in an Infant.


title: New fACEs to the renin-angiotensin system.

text: Inhibition of the angiotensin-converting enzyme (ACE) protects against the progression of several cardiovascular diseases. Recent evidence suggests that some of the beneficial effects of ACE inhibitors can be attributed to the activation of a distinct ACE signaling cascade rather than to the changes in angiotensin II and bradykinin levels. Moreover, at least one other ACE homolog (ACE2) plays a significant role in the regulation of heart and kidney function.


Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors.


title: Sustainable water management in rural and peri-urban areas: what technology do we need to meet the UN millennium development goals?

text: Installation of advanced urban water management systems is one of the most important first steps in the attempt to overcome poverty on earth, outbreak of diseases, crime and even terrorism. Because world wide application of traditional water supply, sewerage and wastewater treatment technology requires financial resources which are basically not available within a reasonable short time frame novel solutions must be found, developed and implemented. The combination of high-tech on-site treatment of the various waste streams generated in households, enterprises and industrial sites, and reuse of the valuable materials obtained from the treatment plants, including the purified water, is one of the options which is investigated by various groups of researchers and technology developers, nowadays. This concept may help meeting the UN Millennium Development Goals, provided people are ready to accept this new way of dealing with household wastes. Education is necessary to build up the foundation which modern water technology can be based upon. In parallel, tailored modifications are to be considered to satisfy the specific demands of local communities. In this context, female participation appears to be extremely important in the decision making process.


title: Hand-assisted laparoscopic live donor nephrectomy - initial experience.

text: INTRODUCTION The advantages of minimally invasive live donor nephrectomy have been well documented, with no adverse effect on graft function. Minimal access nephrectomy has now become the standard of care in many units. We have adopted the hand-assisted laparoscopic live donor (HALLDN) technique, and present our initial experience with the first 24 cases. MATERIAL AND METHODS HALLDNs were performed trans-peritoneally. Primary outcomes included total operative time, warm ischaemic time, time to discharge, and post-operative complications. Warm ischaemic time was measured from the time of clamping the renal artery to the time of perfusing the kidney on the back table. RESULTS Mean total operative time was 143 minutes and mean warm ischaemic time was 188 seconds. A downward trend was displayed for operative times. Mean time to discharge was 60 hours. A right nephrectomy was performed in 2 cases. No surgical morbidity is reported. We describe 1 donor mortality. DISCUSSION Our results compare favourably with those documented in the literature. Aberrant renal vascular anatomy had no adverse effect on operative or warm ischaemic times. HALLDN proved beneficial in patients with a high BMI. CONCLUSION Surgical experience is vital when performing HALLDN. Overcoming the learning curve with an animal model is beneficial.


title: Comparative dynamic distribution of avian infectious bronchitis virus M41, H120, and SAIBK strains by quantitative real-time RT-PCR in SPF chickens.

text: Avian infectious bronchitis is an acute, highly contagious disease of chickens. To study the differences of dynamic distribution between nephropathogenic infectious bronchitis virus (IBV) strains such as SAIBK and other strains (the M41 and H120 strains), relative quantitative real-time reverse transcription-polymerase chain reaction was developed by housekeeping gene selection. Glyceraldehyde-3-phosphate dehydrogenase and Ubiquitin were chosen for normalization in this experimental set. Then nine tissues, the trachea, thymus, liver, spleen, lungs, kidney, pancreas, proventriculus, and bursa of Fabricius, were analyzed and compared to determine the tropism of IBV infection. In this research, the kidney and the lung were established of the most sensitive organs in IBV infection. The pancreas and the liver are candidates for antigen detection. The trachea and the spleen can be used as references for histological diagnosis, but they are not suitable for antigen detection; proventriculus might be an important target in IBV infection; the thymus and the bursa of Fabricius were not sensitive organs in IBV infection.


title: Can team training make surgery safer? Lessons for national implementation of a simulation-based programme.

text: AIM Unintended patient harm is a major contributor to poor outcomes for surgical patients and often reflects failures in teamwork. To address this we developed a Multidisciplinary Operating Room Simulation (MORSim) intervention to improve teamwork in the operating room (OR) and piloted it with 20 OR teams in two of the 20 District Health Boards in New Zealand prior to national implementation. In this study, we describe the experience of those exposed to the intervention, challenges to implementing changes in clinical practice and suggestions for successful implementation of the programme at a regional or national level. METHODS We undertook semi-structured interviews of a stratified random sample of MORSim participants 3-6 months after they attended the course. We explored their experiences of changes in clinical practice following MORSim. Interviews were recorded, transcribed and analysed using a general inductive approach to develop themes into which interview data were coded. Interviews continued to the point of thematic saturation. RESULTS Interviewees described adopting into practice many of the elements of the MORSim intervention and reported positive experiences of change in communication, culture and collaboration. They described sharing MORSim concepts with colleagues and using them in teaching and orientation of new staff. Reported barriers to uptake included uninterested colleagues, limited team orientation, communication hierarchies, insufficient numbers of staff exposed to MORSim and failure to prioritise time for team information sharing such as pre-case briefings. CONCLUSION MORSim appears to have had lasting effects on reported attitudes and behaviours in clinical practice consistent with more effective teamwork and communication. This study adds to the accumulating body of evidence on the value of simulation-based team training and offers suggestions for implementing widespread, regular team training for OR teams.


How to interpret and pursue an abnormal complete blood cell count in adults.


title: Translational frameshifting mediated by a viral sequence in plant cells.

text: It has been proposed that the polymerase gene of barley yellow dwarf virus and related viruses is expressed by a ribosomal frameshift event during translation. The 5' end of this gene overlaps with the 3' end of an upstream gene that is in a different reading frame. The region of overlap is similar to sequences in retro- and coronaviruses that are known to express their polymerase genes by frameshifting. This overlap region includes a "shifty" heptanucleotide, followed by a highly structured region that may contain a pseudoknot. Sequences of 115 or 144 base pairs that span this region from barley yellow dwarf virus (PAV serotype) genomic RNA were introduced into a plasmid, so that a reporter gene could be expressed in plant cells only if a minus one (-1) frameshift event occurred. Frameshifting was detected at a rate of approximately 1%. This frameshifting was abolished when the stop codon at the 3' end of the upstream open reading frame was deleted. A sequence expected to form a strong stem-loop immediately upstream of the frameshift site was unnecessary for frameshifting, and initiation at AUG codons within the stem-loop appeared to be inhibited. Like viruses that infect hosts in other kingdoms, plant viruses also can induce frameshifting in translation of their genes.


title: Recombinant poxviruses as mucosal vaccine vectors.

text: The majority of infections initiate their departure from a mucosal surface, such as Human immunodeficiency virus (HIV), a sexually transmitted virus. Therefore, the induction of mucosal immunity is a high priority in the development of vaccines against mucosal pathogens. The selection of an appropriate antigen delivery system is necessary to induce an efficient mucosal immune response. Poxvirus vectors have been the most intensively studied live recombinant vector, and numerous studies have demonstrated their ability to induce mucosal immune responses against foreign expressed antigens. Previous studies have demonstrated that recombinants based on the attenuated modified vaccinia virus Ankara (MVA) vector were effective in inducing protective responses against different respiratory viruses, such as influenza and respiratory syncytial virus, following immunization via mucosal routes. Recent studies performed in the murine and macaque models have shown that recombinant MVA (rMVA) does not only stimulate HIV-specific immunity in the genital and rectal tracts following mucosal delivery, but can also control simian/human immunodeficiency viraemia and disease progression. In addition, a prime-boost vaccination approach against tuberculosis emphasized the importance of the intranasal rMVA antigen delivery to induce protective immunity against Mycobacterium tuberculosis. The aim of this review is to summarize the studies employing recombinant poxviruses, specifically rMVA as a mucosal delivery vector. The results demonstrate that rMVAs can activate specific immune responses at mucosal surfaces, and encourage further studies to characterize and improve the MVA mucosal immunogenicity of poxvirus vectors.


title: [THE PSYCHOLOGICAL IMPACT OF COVID-19 ON MENTAL HEALTH - LITERATURE REVIEW].

text: INTRODUCTION The spread of epidemics resulting in many deaths has been known since the dawn of civilization, for example, the typhus and smallpox epidemics and the plague. Early in the previous century there was an outbreak of the Spanish Flue and towards the end of the 60's, the AIDS epidemic (HIV). Since the start of the current century, several epidemics broke out and spread to various places around the world, for instance, SARS (Severe Acute Respiratory Syndrome), the Avian Influenza and the Swine Influenza. In 2014 there was an outbreak of Ebola (Ebola virus disease) and in 2015 the Zika virus emerged and there were more. Epidemics cause havoc and impact all areas of life. Each epidemic takes an unfathomable price in lives. It is estimated, for example, that the AIDS epidemic took the lives of some 30 million people. The Corona virus (Covid-19) broke out in China, towards the end of 2019 and spread to most parts of the world. The implications of the outbreak are similar in many countries, among others, due to the uncertainty regarding the way the virus spreads, the appropriate treatment, the lack of vaccination and the high rate of deaths. Naturally, at such times physical protection is a top priority. However, coping with the implications to people's mental health is no less important and these may result in long-term negative impacts.


title: [Comparison among four kits in detection of anti-SARS-CoV IgG in sera of SARS patients].

text: OBJECTIVE To compare the sensitivity and specificity of four kits for detection of anti-severe acute respiratory syndrome (SARS)-CoV IgG in sera of SARS patients. METHODS Anti-SARS-CoV IgG was detected in 99 serial sera from 18 SARS patients and in 123 negative reference sera, using two enzyme linked immunosorbent assays (EIA No. A and No. B) and two indirect immunofluorescence assays (Australian IFA and Euroimmun IFA). RESULTS Anti-SARS-CoV IgG was not detected in sera collected from SARS patients at the first week after onset by any of the four kits, however, it was detectable in sera obtained at the second week of illness by EIA No. B, and two IFA, but not by EIA No. A, with the positive rates of 57.1% (4/7), 57.1% (4/7) and 42.9% (3/7), respectively. The anti-SARS-CoV IgG was first determined in sera on the 9th day by Euroimmun IFA, 12th day by EIA No. B, 13th day by Australian IFA, and 16th day by EIA No. A. The positive rates of antibody on the 3rd week after onset were 84.2% (16/19), 94.7% (18/19), 78.9% (15/19) and 52.6% (10/19) respectively. They were identical since the 4th week after the disease onset. Through detection of 123 negative reference sera, the specificity of EIA No. A and two IFA was 100%, with exception of 94.9% for EIA No. B. CONCLUSION The sensitivity and specificity of the two IFAs were relatively higher than that of the two EIAs. The quality of the two homemade EIAs should be improved.


title: A multiplex reverse transcriptase-PCR assay for the genotyping of avian infectious bronchitis viruses.

text: Infectious bronchitis viruses (IBVs) in Taiwan have been divided into two genogroups, Taiwan group I (TW-I) and Taiwan group II (TW-II). Heterologous Mass-type strains are widely used as vaccines in the field. This work reports on a rapid and reliable multiplex reverse transcriptase-polymerase chain reaction (mRT-PCR) assay for the genotyping of IBVs. Multiplex primer sets were designed to amplify the region covering hypervariable regions 1 and 2 of the S1 glycoprotein gene. Several local strains and commercially available vaccines were used for evaluating the viral genotyping assay, and a number of field isolates were examined for clinical application. The results showed that all of the examined IBVs were accurately genotyped by identifying the corresponding bands on agarose gels (TW-I: 322 bp, TW-II: 161 bp, Mass type: 256 bp) after the mRT-PCR, in agreement with the viral genome sequence data. The mRT-PCR assay was able to detect viral RNA copies as low as 10(3), 10(50, and 10(3) for the TW-I, TW-II, and Mass-type strains, respectively. The mRT-PCR assay accurately detected and discriminated vaccine viruses from wildtype strains in the field. This assay may be beneficial for virus identification and differentiation in routine disease surveillance.


title: Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins.

text: A series of publications in the 1950s described a kidney disease in Bulgaria, the former Yugoslavia and Romania that became known as Balkan endemic nephropathy (BEN). The disease was qualified by World Health Organisation (WHO) experts as 'progressive and very gradually developing renal failure with insidious onset.... The last stage shows marked fibrosis...'. BEN is characterized by tubular degeneration, interstitial fibrosis and hyalinization of glomeruli accompanied by enzymuria and impaired renal function without nephrotic syndrome. Later, an association between BEN and tumours of the kidney pelvis and ureter was recognized, so that the problem of BEN became not only nephrological, but also oncological. There may also be an association with increased urinary bladder cancer incidence, although many confounding factors may interfere in the analysis of data for this organ. In view of the very intimate association between BEN and the urinary tract tumours (UTT), the term 'endemic uropathy' has been proposed. Several hypothesis concerning the aetiology of these diseases has been investigated, which include: predisposing genes factors, environmental factors (heavy metals, minerals, bacteria, leptospira, viruses, fungal toxins and, most recently, pliocene lignites). This paper reviews the different hypotheses about the aetiology of endemic uropathy and pays particular attention to the role of fungal toxins.