title: Profiles of IgG antibodies to nucleocapsid and spike proteins of the SARS-associated coronavirus in SARS patients.

text: To evaluate humoral immunity against the SARS-associated coronavirus (SARS-CoV), we studied the profiles of IgG antibodies to the nucleocapsid (N) and spike (S) proteins of SARS-CoV. Serum specimens from 10 SARS patients were analyzed by Western blotting and an enzyme-linked immunosorbent assay (ELISA) using purified recombinant N and truncated S (S1, S2, and S3) proteins as antigens. Western blotting results demonstrated that 100% of the SARS patients tested positive for N protein-specific antibodies, 50% for S1 protein-specific antibodies, 30% for S2 protein-specific antibodies, and 70% for S3 protein-specific antibodies. The ELISA results, which showed positive rates of IgG reactivity against recombinant proteins N, S1, S2, and S3, were, respectively, 28.57, 14.29, 14.29, and 14.29% at week 1, 77.78, 55.56, 44.44, and 66.67% at week 2, 100, 75, 75, and 87.5% at week 3, and 100, 77.78, 77.78, and 88.89% after 3 weeks. The average titers of IgG against recombinant proteins N, S1, S2, and S3 were, respectively, 691, 56, 38, and 84 after 3 weeks. These results suggest that the recombinant proteins N and S3 are potentially useful antigens for a serological diagnosis of SARS. In consideration of possible cross-reactivity among N proteins of SARS-CoV and other coronaviruses, immunoassays using recombinant N protein in combination with S3 as antigens might improve the specificity of SARS diagnoses.


title: Prevalence of antibodies to selected viral pathogens in wild boars (Sus scrofa) in Croatia in 2005-06 and 2009-10.

text: We determined prevalence of antibody to selected viral pathogens important for domestic pigs and livestock in 556 wild boar (Sus scrofa) sera collected during 2005-06 and 2009-10 in four counties in Croatia. These counties account for an important part of the Croatian commercial pig production and have a high density of wild boars. Samples were tested for antibodies to porcine parvovirus (PPV), Aujeszky's disease virus (ADV), porcine circovirus type 2 (PCV2), swine influenza virus, porcine respiratory and reproductive syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV), transmissible gastroenteritis virus, and swine vesicular disease virus (SVDV). Antibodies to all of the infectious pathogens except SVDV were detected. There was a statistically significant difference in prevalence between the two periods for PPV, ADV, PCV2, PRRSV, and PRCV, with a higher prevalence of PPV and ADV in the 2009-10 period (P<0.05). During the same period, the prevalence of PCV2, PRRSV, and PRCV was lower (P<0.05). Our results provide information on the current disease exposure and health status of wild boars in Croatia and suggest that wild boars may act as a reservoir for several pathogens and a source of infection for domestic pigs and other livestock as well as humans, especially for ADV.


title: [Drug transport in the respiratory epithelium].

text: The aerosolic administration of peptidomimetic drugs with a peptide backbone may play a crucial role in the future treatment of diseases. Especially rational drug design offers an option to synthesize new drugs that are carried by specific drug transporters. Out of the presently identified transporter proteins PEPT1 and PEPT2, the high-affinity transporter PEPT2 is found in the respiratory tract. The transporter possess 12 membrane spanning domains and catalyses an electrogenic uphill drug transport using a transmembrane electrochemical proton gradient. PEPT2 is expressed in the bronchial epithelium and in alveolar type II pneumocytes in human airways. Kinetic studies demonstrated that peptidomimetic compounds including antibiotic, antiviral and antineoplastic drugs are carried by PEPT2. The transporter also carries delta-aminolevulinic acid into the airways. This molecule can be used for the diagnostics of pulmonary neoplasms and for photodynamic therapy. Using the recently published data on minimal structural requirements for PEPT2-substrates, rational drug design may lead to a new generation of respiratory drugs and prodrugs, which are delivered to the airways via the molecular mechanisms of the PEPT2 transport system.


title: [Lung pathology and pathogenesis of severe acute respiratory syndrome: a report of six full autopsies].

text: OBJECTIVE Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in November 2002. The SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear. METHODS Post-mortem lung samples from six patients who died from SARS from April to July 2003 were studied by light and electron microscopy, Masson trichromal staining and immunohistochemistry. Evidence of infection with the SARS-CoV was determined by reverse-transcription PCR (RT-PCR) , serological examination and electron microscopy. RESULTS Four of six patients had serological and RT-PCR evidence of recent infection of SARS-CoV. Morphologic changes are summarized as follows: (1) Diffuse and bilateral lung consolidation was seen in all patients (6/6) with increasing lung weight. (2) Diffuse alveolar damage was universal (6/6) with hyaline membrane formation (6/6), intra-alveolar edema/hemorrhage (6/6), fibrin deposition (6/6), pneumocyte desquamation (6/6). A marked disruption in the integrity of the alveolar epithelium was confirmed by immunostaining for the epithelial marker AE1/AE3 (6/6). (3) Type II pneumocytes, with mild hyperplasia, atypia, cytomegaly with granular amphophilic cytoplasm and intracytoplasmic lipid accumulation (5/6). (4) Giant cells in the alveoli were seen in five of 6 patients (5/6) , most of which were positive for the epithelial marker AE1/AE3 (5/6), but some cells were positive for the macrophage marker CD68(2/6). (5) A pronounced increase of macrophages were seen in the alveoli and the interstitium of the lung (6/6), which was confirmed by histological study and immunohistochemistry. (6) Haemophagocytosis was present in five of the 6 patients(5/6). (7) Lung fibrosis was seen in five patients(5/6), with alveolar septa and interstitium thickening(5/6), intraalveolar organizing exudates (6/6) and pleura thickening (4/6). Proliferation of collagen was confirmed by Masson trichromal staining, most of which was type III collagen by immunostaining. The formation of distinctive fibroblast/myofibroblast foci was seen in five patients (5/6) by light microscopy and immunochemistry. (8) Squamous metaplasia of bronchial mucosa was seen in five patients(5/6). (9) Thrombi was seen in all patients(6/6). (10) Accompanying infection was present in two patients, one was bacteria, the other was fungus. In addition, electron microscopy revealed viral particles in the cytoplasm of alveolar epithelial cells and endothelial cells corresponding to coronavirus. CONCLUSION Direct injury of SARS-CoV on alveolar epithelium, prominent macrophage infiltration and distinctive fibroblast/myofibroblast proliferation may play major roles in the pathogenesis of SARS.


title: Acute flaccid paralysis following enterovirus D68 associated pneumonia, France, 2014.

text: Human enterovirus D68 (EV-D68) is known to be associated with mild to severe respiratory infections. Recent reports in the United States and Canada of acute flaccid paralysis (AFP) in children with detection of EV-D68 in respiratory samples have raised concerns about the aetiological role of this EV type in severe neurological disease. This case study is the first report of AFP following EV-D68 infection in Europe.


Strategies to prevent central line-associated bloodstream infections in acute care hospitals: 2014 update.


title: Evaluation of the xenobiotic reaction against hyaluronate-based bioresorbable membrane in the abdominal cavity.

text: Postoperative abdominal adhesions are one of the most common post-laparotomy complications observed. Several types of adhesion preventative agents are available and their effectiveness and adverse impact have been clinically evaluated in previous studies. However, few basic studies have tested whether those agents do not trigger any unwanted xenobiotic reaction, which makes some surgeons hesitant to use them. To clarify this point, we investigated whether the adhesion preventative agent Seprafilm® (KAKEN PHARMACEUTICAL CO., LTD., Tokyo, Japan), one of the most widely used hyaluronate-based bioresorbable membrane (HBBM), can trigger an inflammatory response in normal abdominal tissue and delay the healing process. The rat underwent laparotomy and a HBBM was placed directly below the incision. Tissue samples at the incision and away from the incision (normal tissue) were harvested and inflammatory response and fibrosis were evaluated using quantitative PCR and histological scoring. We found that HBBM did not induce inflammatory cytokine expression at mRNA level in the peritoneal wall tissue or modify the fibrosis process in the abdominal cavity. These findings confirm the safety of using HBBM for the prevention of adhesion development post-laparotomy.


title: Mucinous cystadenocarcinoma of the pancreas with anaplastic carcinoma: A case report and review of the literature.

text: Few reports of mucinous cystic neoplasm (MCN) in association with anaplastic carcinoma exist. The present study reported an unusual case of a 25-year-old female exhibiting large pancreatic MCN with anaplastic carcinoma. Notably, the patient was a Jehovah's Witness and therefore refused any blood transfusions. Preoperative diagnosis was invasive pancreatic MCN measuring 12.5 cm with ascites. Distal pancreatectomy was performed in combination with splenectomy and partial resection of the transverse colon. Intraoperative estimated blood loss was 400 ml, therefore a blood transfusion was not required. The patient had an uneventful postoperative course. The pathological diagnosis was mucinous cystadenocarcinoma of the pancreas with anaplastic carcinoma. Although the patient underwent postoperative adjuvant chemotherapy with gemcitabine and oral fluoropyrimidine (S-1), recurrence with peritoneal dissemination was detected 20 months following surgery and the patient succumbed to the recurrence 32 months following surgery. To the best of our knowledge, this is the first case report of MCN with anaplastic carcinoma of the pancreas in a Jehovah's Witness patient undergoing pancreatic surgery.


API Guidelines on Immunizations during COVID 19 Pandemic.


title: Clinical features, treatments and outcomes of influenza A (H1N1) 2009 among the hospitalized patients in the clinic for infectious diseases in Novi Sad.

text: BACKGROUND/AIM Most infections caused by influenza A (H1N1) 2009 virus are presented by mild respiratory symptoms. However, some patients required admission to the intensive care unit (ICU). In this article we aimed to describe the clinical and laboratory characteristics of the patients with influenza A (H1N1) 2009, antiviral therapy use, the disease outcome and risk factors associated with the severe disease. METHODS The patients with the signs and simptoms of novel influenza A (H1N1) 2009, admitted to the Clinic for Infectious Disease in Novi Sad, were evaluated. The study included 293 patients hospitalized between October 2009 and February 2010. Basic demographic data, underlying medical conditions, clinical signs and symptoms, duration of the disease before the admission, laboratory tests, radiographic findings, treatment, and the final outcome (survived, died) were all noted. Factors associated with severe disease requiring ICU admission were determined by comparing the ICU cases with control groups of the patients admitted to the hospital but not to ICU. RESULTS The average age of the patients was 32.72 years. A total of 114 (38.9%) of the patients had an underlying medical condition. Asthma and chronic obstructive pulmonary disease were present in 44 (15.01%) of the patients, chronic cardiovascular diseases in 28 (9.56%), diabetes mellitus in 16 (5.46%), malignity in 15 (4.44%) of the patients and 11 (3.75%) of the patients were pregnant. Fever was registered in 282 (96.24%), myalgias in 119 (40.61%), headache in 48 (16.38%), cough in 240 (81.91%), sore throat in 25 (8.53%), runny nose and sneezing in 17 (5.8%) and dyspnea in 110 (37.54%) of the patients. A total of 192 (65.53%) had radiological findings that were consistent with pneumonia. A total of 154 (56.61%) of the patients received antiviral therapy within 48 h. A total of 280 (96.24%) patients were discharged and 13 (4.44%) were transferred to ICU. Fatal outcome was noticed in 2/13 (15.3%) ICU treated patients and 11/13 (84.7%) patients survived. The median time from the onset of illness to the initiation of antiviral treatment was 7.1 days for the patients admitted to ICU and 3.2 days for non-ICU patients (p < 0.05). Low blood oxygen saturation (SaO2 < or = 92%) was more common in ICU admitted patients, 10/13 (76,92%), compared to 28/280 (10%) non-ICU admitted ones (p < 0.01). Serum C-reactive protein (CRP) levels > 200 mg/L were noticed in 9/13 (69.23%) patients admitted to ICU and 85/280 (30.35%) patients who were not (p < 0.05). CONCLUSION Most novel influenza A (H1N1) 2009 infections presented mild respiratory disease. Prompt antiviral therapy in patients with A (H1N1) virus infection seem to be the best approach to avoid serious form of the disease. Special attention should be payed to patients having low level of peripheral oxygen saturation and raised CRP serum level.


title: [Cloning of ACE-2 gene encoding the functional receptor for the SARS coronavirus and its expression in eukaryotic cells].

text: OBJECTIVE Angiotensin-converting enzyme 2 (ACE-2) has been identified as a functional receptor of severe acute respiratory syndrome coronavirus (SARS-CoV), so its gene was cloned and eukaryotic expressed for further insight into mechanisms in SARS-CoV entry and pathogenesis, as well as development of a safe and reliable neutralization assay for SARS-CoV. METHODS Total RNA was extracted from right atrial tissue of a patient with right heart failure resected during a valvular replacement surgery by Trizol one-step method, and the full-length ACE-2 encoding gene was acquired by RT-nested-PCR. The ACE-2 encoding gene was then cloned into pcDNA4/HisMax-TOPO eukaryotic expression vector to construct the recombinant plasmid pcDNA4/ ACE-2, which was then transfected into 293 T cell and ACE-2 eukaryotic transient expression was detected by Western Blot. Syncytia inhibition assay was established to detect SARS-CoV neutralizing antibody, and compared parallelly with SARS pseudovirus neutralization assay. RESULTS The recombinant plasmid pcDNA4/ ACE-2 could express ACE-2 protein in eukaryotic cells and induce cell-cell fusion between S protein- and ACE2-expressing cells. This cell-cell fusion assay could be used to detect SARS-CoV neutralizing antibody. CONCLUSION SARS-CoV receptor ACE-2 gene was successfully cloned and eukaryotic expressed, and used to establish syncytia inhibition assay for SARS-CoV neutralizing antibody assay.


title: [Healthcare management during COVID-19 pandemia.]

text: OBJECTIVES To describe the organization of a hospital during the COVID-19 pandemic, paying attention to both organizational and leadership aspects, and considering all hospital areas, including the operating room.MATERIAL AND METHODS: Review of the literatureregarding the organizational councils for hospital management within the pandemic. In addition, the recommendations of societies, institutions such as the WHO, the CDC, the ECDC, the National Ministry of Health and the Ministry of Health of Madrid and the center's own experience have been taken into account. RESULTS Description of the key elements for the organization,as well as the different areas of action within a hospital: emergencies, consultations, hospitalization and operating rooms. CONCLUSIONS Management during a pandemic requires a high degree of agility in response and plasticity in people. All hospital structures must adapt to a situationfor which they have not been conceived and all staff must place themselves at the service of a disease that conditions all decisions. Being able to adapt and try to anticipate what is going to happen are the keys to success.


title: A history of biological disasters of animal origin in North America.

text: This paper examines past occurrences in North America relevant to the possibility of biological disasters with animal origins. With respect to naturally occurring animal disease outbreaks, North America, while not as adversely affected by epizootics as other regions, has had its fair share of such outbreaks of both 'traditional' and emerging animal diseases. The traditional category includes such diseases as anthrax, classical swine fever, bluetongue, brucellosis, foot and mouth disease, and the family of equine encephalomyelitis viruses. The emerging diseases include relatively more recent culprits such as postweaning multisystemic wasting syndrome, poultry enteritis mortality syndrome, and newly discovered examples of the transmissible spongiform encephalopathies. Additionally, several serious diseases of human beings that involve animal vectors or reservoirs occur naturally in North America or have emerged in recent decades; these include plague, hantavirus, monkeypox, West Nile virus and avian-derived influenza. At the same time, there have been very few intentional attacks on livestock using biological agents and no recorded cases in North America of animals intentionally being used to transmit disease to humans. According to the historical record, therefore, naturally occurring emerging zoonoses probably constitute the greatest threat in terms of biological disasters with animal origins. However, some of the general trends in terrorist activity, such as the intensification of activities by animal rights extremists against facilities undertaking animal research, mean that the possibility of intentional animal-related biological disasters should not be discounted.


title: [Electron microscopic virus detection in fecal samples from swine with enteric diseases between 1981 and 1987].

text: Results of electron microscopical studies of 517 fecal samples from diarrhoeic pigs out of the years 1981 and 1987 were reported. Coronavirus was found in 26.3%, rotavirus in 4.3%, parvovirus in 2.1%, coronavirus like particles in 2.9% and picornavirus like particles in 2.3% of the samples. In some cases (2.3%) double infections could be detected occurring as well between corona- and rotavirus, parvovirus or picornavirus like particles as between rotavirus and parvovirus and picornavirus like particles, respectively. The results were reported annually.


title: Human immunodeficiency virus type 1 (HIV-1) tat induces nitric-oxide synthase in human astroglia.

text: Human immunodeficiency virus type 1 (HIV-1) infection is known to cause neuronal injury and dementia in a significant proportion of patients. However, the mechanism by which HIV-1 mediates its deleterious effects in the brain is poorly defined. The present study was undertaken to investigate the effect of the HIV-1 tat gene on the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astroglia. Expression of the tat gene as RSV-tat but not that of the CAT gene as RSV-CAT in U373MG astroglial cells led to the induction of NO production and the expression of iNOS protein and mRNA. Induction of NO production by recombinant HIV-1 Tat protein and inhibition of RSV-tat-induced NO production by anti-Tat antibodies suggest that RSV-tat-induced production of NO is dependent on Tat and that Tat is secreted from RSV-tat-transfected astroglia. Similar to U373MG astroglial cells, RSV-tat also induced the production of NO in human primary astroglia. The induction of human iNOS promoter-derived luciferase activity by the expression of RSV-tat suggests that RSV-tat induces the transcription of iNOS. To understand the mechanism of induction of iNOS, we investigated the role of NF-kappaB and C/EBPbeta, transcription factors responsible for the induction of iNOS. Activation of NF-kappaB as well as C/EBPbeta by RSV-tat, stimulation of RSV-tat-induced production of NO by the wild type of p65 and C/EBPbeta, and inhibition of RSV-tat-induced production of NO by deltap65, a dominant-negative mutant of p65, and deltaC/EBPbeta, a dominant-negative mutant of C/EBPbeta, suggest that RSV-tat induces iNOS through the activation of NF-kappaB and C/EBPbeta. In addition, we show that extracellular signal-regulated kinase (ERK) but not that p38 mitogen-activated protein kinase (MAPK) is involved in RSV-tat induced production of NO. Interestingly, PD98059, an inhibitor of the ERK pathway, and deltaERK2, a dominant-negative mutant of ERK2, inhibited RSV-tat-induced production of NO through the inhibition of C/EBPbeta but not that of NF-kappaB. This study illustrates a novel role for HIV-1 tat in inducing the expression of iNOS in human astrocytes that may participate in the pathogenesis of HIV-associated dementia.


Unseasonal outbreaks of husk in dairy cattle.


title: Public health measures to control the spread of the severe acute respiratory syndrome during the outbreak in Toronto.

text: BACKGROUND Toronto was the site of North America's largest outbreak of the severe acute respiratory syndrome (SARS). An understanding of the patterns of transmission and the effects on public health in relation to control measures that were taken will help health officials prepare for any future outbreaks. METHODS We analyzed SARS case, quarantine, and hotline records in relation to control measures. The two phases of the outbreak were compared. RESULTS Toronto Public Health investigated 2132 potential cases of SARS, identified 23,103 contacts of SARS patients as requiring quarantine, and logged 316,615 calls on its SARS hotline. In Toronto, 225 residents met the case definition of SARS, and all but 3 travel-related cases were linked to the index patient, from Hong Kong. SARS spread to 11 (58 percent) of Toronto's acute care hospitals. Unrecognized SARS among in-patients with underlying illness caused a resurgence, or a second phase, of the outbreak, which was finally controlled through active surveillance of hospitalized patients. In response to the control measures of Toronto Public Health, the number of persons who were exposed to SARS in nonhospital and nonhousehold settings dropped from 20 (13 percent) before the control measures were instituted (phase 1) to 0 afterward (phase 2). The number of patients who were exposed while in a hospital ward rose from 25 (17 percent) in phase 1 to 68 (88 percent) in phase 2, and the number exposed while in the intensive care unit dropped from 13 (9 percent) in phase 1 to 0 in phase 2. Community spread (the length of the chains of transmission outside of hospital settings) was significantly reduced in phase 2 of the outbreak (P<0.001). CONCLUSIONS The transmission of SARS in Toronto was limited primarily to hospitals and to households that had had contact with patients. For every case of SARS, health authorities should expect to quarantine up to 100 contacts of the patients and to investigate 8 possible cases. During an outbreak, active in-hospital surveillance for SARS-like illnesses and heightened infection-control measures are essential.


title: Q&A: Preparing for Pandemic, An Interview with Umair Shah, MD, Harris County Public Health.

text: Umair Shah, MD, Harris County Public Health executive director, on how COVID-19 has exposed gaps in the public health system.


title: Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase.

text: The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. In order to understand the active form and the substrate specificity of the enzyme, we have cloned, expressed, and purified SARS 3C-like proteinase. Analytic gel filtration shows a mixture of monomer and dimer at a protein concentration of 4 mg/ml and mostly monomer at 0.2 mg/ml, which correspond to the concentration used in the enzyme assays. The linear decrease of the enzymatic-specific activity with the decrease of enzyme concentration revealed that only the dimeric form is active and the dimeric interface could be targeted for structural-based drug design against SARS 3C-like proteinase. By using a high pressure liquid chromatography assay, SARS 3C-like proteinase was shown to cut the 11 peptides covering all of the 11 cleavage sites on the viral polyprotein with different efficiency. The two peptides corresponding to the two self-cleavage sites are the two with highest cleavage efficiency, whereas peptides with non-canonical residues at P2 or P1' positions react slower. The P2 position of the substrates seems to favor large hydrophobic residues. Secondary structure studies for the peptide substrates revealed that substrates with more beta-sheetlike structure tend to react fast. This study provides a basic understanding of the enzyme catalysis and a full substrate specificity spectrum for SARS 3C-like proteinase, which are helpful for structural-based inhibitor design against SARS and other coronavirus.


title: [New possibilities in oral immunoprophylaxis of newborn diarrhea in calves--a field study using specific egg antibodies].

text: To investigate the effect of oral immunoprophylaxis in diarrhea of newborn calves egg powder with antibodies specific to E. coli K99 (ETEC) and rotavirus were used in a field trial in south west Germany. Fourteen farms with a total of 105 calves were selected. Egg powder (21 g per day) was fed as a supplement to the regular diet for the first 14 days after birth. Animals of the control group received egg powder derived from hens not immunized with the antigens. Frequency, duration and severity of diarrhea, fecal dry matter and weight gain were examined in order to evaluate the influence of the specific egg powder. Using a Lactovac test kit pathogens were detected in the feces of 76.2% of the calves, with 24.7% infected with E. coli K99, 39.1% with rotavirus, 19.0% with coronavirus and 32.4% with cryptosporidia. An overall reduction in diarrhea frequency from 68.5% to 52.9% was observed in calves fed with specific antibodies. Animals with an E. coli K99 infection showed a reduction from 92.3% to 30.7% and those infected exclusively with E. coli K99 from 83.3% to 0%. The duration of diarrhea was significantly reduced (42 h) in animals fed with specific antibodies in comparison to the control animals (60 h). With the exception of animals infected with coronavirus a marked reduction in the severity of diarrhea was observed in antibody treated calves. During the first 14 days after birth antibody treated calves showed a weight gain of 5.6 kg on average in comparison with 3.5 kg in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


title: The effects of QuikClot Combat Gauze and movement on hemorrhage control in a porcine model.

text: The purpose of this study was twofold: (1) to examine the effectiveness of QuikClot Combat Gauze (QCG) compared to a control group and (2) investigate the effect of movement on hemorrhage control when QCG is employed. This was a prospective, experimental design employing an established porcine model of uncontrolled hemorrhage. The minimum number of animals (n = 11 per group) was used to obtain a statistically valid result. There were no statistically significant differences between the groups (p > 0.05) indicating that the groups were equivalent on the following parameters: activating clotting time, the subject weights, core body temperatures, amount of 1 minute hemorrhage, arterial blood pressures, and the amount and percentage of total blood volume. There were significant differences in the amount of hemorrhage (p = 0.018) and the number of movements (p = 0.000) between the QCG and control. QCG is statistically and clinically superior at controlling hemorrhage compared to the standard pressure dressing control group. Furthermore, it produces a more robust clot that can withstand significant movement. In conclusion, QCG is an effective hemostatic agent for use in civilian and military trauma management.


title: Lumbar subarachnoid hematoma following an epidural blood patch for meningeal puncture headache related to the implantation of an intrathecal drug delivery system.

text: Persistent meningeal puncture headache (MPH) is a known complication following both intentional and unintentional puncture of the dura mater. We present a case of persistent MPH following implantation of an intrathecal drug delivery system (IDDS). Two separate epidural blood patches (EBP) were performed under radiographic guidance with contrast visualization of the epidural space on postoperative days 16 and 28, respectively. The case was complicated by the development of a symptomatic lumbar subarachnoid hematoma diagnosed on postoperative day 35. The patient subsequently underwent a laminectomy, evacuation of the hematoma, and explanation of the IDDS. This case illustrates a potential unique morbidity associated with the EBP in a patient with an IDDS. The report concludes with a brief review of MPH followed by a discussion of possible mechanisms underlying this complication.


title: [Analysis of mortal risk factors in 12 patients with severe acute respiratory syndrome].

text: OBJECTIVE To investigate the risk factors in the dead patients with severe acute respiratory syndrome (SARS). METHODS The retrospective analyses were made on 12 dead cases and 32 recovered cases with SARS. RESULTS The mean age was 67 years old in 12 dead cases with SARS and was 42 in recovered control group. There were 1-5 other basic diseases in 5 cases of death group. The states of dead patients were severe and the deterioration of patients' condition was rapid. The CD 4 and CD 8 T lymphocytes in peripheral blood were (416.6+/-235.0) cells/microl and (296.1+/-181.5)cells/microl in survival patients and (143.8+/-78.1)cells/microl, (103.6+/-63.2) cells/microl in dead patients, they often decreased compared to the normal values, especially in dead cases. Five cases were infected with bacteria in 12 dead cases, among them 3 were infected with fungus and 2 were septicemia. In dead group, the occurrence rates of electrolyte maladjustment and kidney injury were 41.67 percent. Invasive ventilation was used in 10 cases and death rate was 80.0 percent, among them 5 patients were infected with bacteria. None was dead in the patients with non-invasive ventilation. CONCLUSION The age and basic diseases are the main mortal risk factors in SARS. Other risk factors include the decline of immune function, secondary infection, complications and use of invasive ventilation.


title: Prevalence of thermophilic Campylobacter species in household cats and dogs in Ireland.

text: Rectal swabs were collected from 147 household dogs and 35 household cats, including healthy animals, animals with gastrointestinal signs and animals with a variety of medical and surgical conditions. A combination of selective culture methods was used to optimise the recovery of Campylobacter species, and a PCR was used to confirm their isolation and to identify the species. The overall prevalence of Campylobacter species was 42.9 per cent in the cats and 41.5 per cent in the dogs. Campylobacter upsaliensis was the species most commonly isolated from the dogs and cats, and Campylobacter jejuni was the second most commonly isolated. Particularly high prevalences were detected in the few cats and dogs with diarrhoea, and in the cats and dogs that were six months old or younger.


title: Bacterial and fungal infections among patients with SARS-CoV-2 pneumonia.

text: We reviewed studies reporting bacterial and fungal co-infections in patients with COVID-19. The majority were retrospective studies with poor quality data biased with short follow-up and selection of patients. Septic shock was reported in 4% to 33.1% of patients. Seventy-one to 100% of patients received antibacterial treatments. Invasive pulmonary aspergillosis seems to be an increasingly observed complication in critically ill patients with SARS-CoV-2 infection as previously reported in patients hospitalized in ICU with severe influenza. High quality prospective studies are urgently needed to verify the incidence of bacterial and fungal infections and their role on the outcome of COVID-19.


Department of Health and Human Services, National Institutes of Health. Recombinant DNA research: proposed actions under guidelines.


title: Proteomic data mining using predicted peptide chromatographic retention times.

text: Correct identification of proteins from peptide fragments is important for proteomic analyses. Peptides are initially separated by Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) before Mass Spectrometry (MS) identification. At the present time, peptide fragment retention (separation) time is not used as a useful scoring filter for identification of the peptide fragments and their parent proteins. In the present paper, we present a new web-based tool for the prediction of peptide fragment retention times and its use in compiling a database of approximately 133,000 peptide fragments computationally obtained by digestion with trypsin of 4,265 E. coli - K12 proteins. The retention calculation is based on the described formulae and the fragments/protein identification was carried out using a simple search-scoring algorithm.


title: Endovascular Retrieval of Entrapped Elephant Trunk Graft During Complex Hybrid Aortic Arch Repair.

text: Entrapment of the elephant trunk graft within the false lumen is a rare complication of surgical repair of an aortic dissection. This is normally retrieved by emergent open surgery. We describe a technique of endovascular retrieval of the dislodged graft, during hybrid aortic arch repair. The elephant trunk was cannulated through and through from a femoral access and the free end of the wire was snared and retrieved from a brachial access. The wire was externalised from both accesses and was used to reposition the graft into the true lumen using a body flossing technique.


title: The toxicological response of Brazilian chrysotile asbestos: a multidose subchronic 90-day inhalation toxicology study with 92-day recovery to assess cellular and pathological response.

text: Inhalation toxicology studies with chrysotile asbestos have in the past been performed at exceedingly high doses without consideration of fiber number or dimensions. As such, the exposures have exceeded lung overload levels, making quantitative assessment of these studies difficult if not impossible. To assess the cellular and pathological response in the rat lung to a well-characterized aerosol of chrysotile asbestos, a 90-day subchronic inhalation toxicology study was performed using a commercial Brazilian chrysotile (CA 300). The protocol was based on that established by the European Commission for the evaluation of synthetic vitreous fibers. The study was also designed to assess the potential for reversibility of any such changes and to permit association of responses with fiber dose in the lung and the influence of fiber length. Wistar male rats were randomly assigned to an air control group and to 2 CA 300 exposure groups at mean fiber aerosol concentrations of 76 fibers L > 20 microm/cm3 (3413 total fibers/cm3; 536 WHO fibers/cm3) or 207 fibers L > 20 microm/cm3 (8941 total fibers/cm3; 1429 WHO fibers/cm3). The animals were exposed using a flow-past, nose-only exposure system for 5 days/wk, 6 h/day, during 13 consecutive weeks (65 exposures), followed by a subsequent nonexposure period lasting for 92 days. Animals were sacrificed after cessation of exposure and after 50 and 92 days of nonexposure recovery. At each sacrifice, subgroups of rats were assessed for the determination of the lung burden; histopathological examination; cell proliferation response; bronchoalveolar lavage with the determination of inflammatory cells; clinical biochemistry; and for analysis by confocal microscopy. Through 90 days of exposure and 92 days of recovery, chrysotile at a mean exposure of 76 fibers L > 20 microm/cm3 (3413 total fibers/cm3) resulted in no fibrosis (Wagner score 1.8 to 2.6) at any time point. The long chrysotile fibers were observed to break apart into small particles and smaller fibers. In vitro modeling has indicated that these particles are essentially amorphous silica. At an exposure concentration of 207 fibers L > 20 microm/cm3 (8941 total fibers/cm3) slight fibrosis was observed. In comparison with other studies, chrysotile produced less inflammatory response than the biosoluble synthetic vitreous fiber CMS. As predicted by the recent biopersistence studies on chrysotile, this study clearly shows that at that at an exposure concentration 5000 times greater than the U.S. threshold limit value of 0.1 f(WHO)/cm3, chrysotile produces no significant pathological response.


title: Hepatic toxicity after radioembolization of the liver using (90)Y-microspheres: sequential lobar versus whole liver approach.

text: PURPOSE (90)Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus "whole liver" (90)Y-radioembolization. METHODS Thirty-four patients with liver malignancy in noncirrhotic livers were included; (90)Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. RESULTS Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 μmol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043). CONCLUSIONS Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.


title: Susceptibility of a fetal tongue cell line derived from bighorn sheep to five serotypes of bluetongue virus and its potential for the isolation of viruses.

text: A cell line (BHFTE) was derived from a tongue explant of a bighorn sheep fetus (Ovis canadensis nelsoni). The cells have been maintained through 23 serial passages, and the modal number of chromosomes was calculated to be 55. Monolayer cultures were shown to be susceptible to various viruses, including bluetongue virus (BTV). Of 5 BTV serotypes (2, 10, 11, 13, and 17) tested, each produced a cytopathic effect (CPE) on initial passage at 33 C. A field isolate (serotype 10) of BTV from a black-tailed deer (Odocoileus hemionus columbianus) in its second passage in Vero-M cells also produced CPE when inoculated into BHFTE cells. Antigens of BTV were demonstrated by direct immunofluorescence in the cytoplasm of BHFTE cells inoculated with homogenates of chicken embryos injected with clinical specimens from a domestic sheep and an Arabian oryx (Oryx gazella leucoryx). A suspension of BTV-infected gnats (Culicoides spp.) produced CPE and BTV-specific fluorescence on the first passage in cells inoculated with a suspension of blood from sheep experimentally infected with BTV. Additionally, selected bovine viruses induced CPE in the cells. The cell line, which is free of mycoplasma and bovine viral diarrhea virus contamination, may be useful in diagnostic medicine and research involving the ruminant species.


title: Respiratory viral infections in transplant recipients.

text: A wide range of viruses affect the respiratory tract of transplant recipients, including adenovirus, influenza, human metapneumovirus, parainfluenza virus, respiratory syncytial virus (RSV) and rhinovirus. Prospective studies using contemporary diagnostic techniques have recently improved our understanding of the epidemiology and importance of these respiratory viruses among transplant recipients. From these studies, rhinovirus, in particular, has been shown to be one of the most common causes of infection in stem cell and lung transplant recipients. In addition to epidemiological data, recent studies have also advanced our understanding of management of influenza, adenovirus, and RSV infections among transplant recipients.


title: Relatedness of rabbit coronavirus to other coronaviruses.

text: Rabbit coronavirus (RbCV) was apparently first encountered in 1961 when Scandinavian investigators observed occasional mortality in rabbits used to propagate the Nichols strain of Treponema pallidum. Mortality rates reached 50 percent by 1968 and 75 percent by 1970. Contaminated samples of T. pallidum were brought to the Johns Hopkins University School of Medicine, a World Health Organization center for the study of treponematoses. There it was established that the causative agent was filterable, the heart was the target organ, and the agent was determined by electron microscopy to be a coronavirus. Also, complement fixing antibodies to the human coronaviruses 229E (two way cross) and 0C43 (one way cross) were demonstrated in surviving rabbits. Immunofluorescent staining with anti-229E serum localized fluorescence in the interstitial tissue of the myocardium. Antiserum to RbCV cross reacted with coronaviruses of three other diseases, feline infectious peritonitis (FIPV), canine coronavirus diarrhea (CCV), and transmissible gastroenteritis (TGEV) by radioimmunoassay. In plaque neutralization tests, a slight reduction was observed against TGE and CCV but not against FIP. Antiserum to 229EV, CCV, FIPV and to a lesser degree TGEV partially blocked the clinical course of the disease and reduced mortality. Slight protection was afforded rabbits by vaccination with, in descending order of survivors, CCV, FIPV, and TGEV. Vaccination with calf diarrhea coronavirus (CDCV) provided no protection.


Brinzolamide induced reversible corneal decompensation.


title: Otitis media with effusion: an effort to understand and clarify the uncertainties.

text: Otitis media with effusion--defined as the accumulation of middle-ear effusion behind an intact tympanic membrane without signs or symptoms of acute infection--is one of the most common causes of hearing loss in children in developed countries, potentially leading to language deficits. Although treatment of chronic or relapsing otitis media with effusion is considered imperative, none of the preventative or nonsurgical management measures currently available have proven effective. Tympanostomy tube placement remains the recommended treatment option for high-risk children or for cases of unresponsive otitis media with effusion. This can be attributed to the uncertainties surrounding its pathogenesis. Multiple factors and several possible pathogenetic models have been proposed to explain the production and persistence of middle-ear effusion; only a few of them are supported by sufficient evidence. In this review, the authors will present current knowledge on the pathogenesis, consequences, diagnosis and management of otitis media with effusion. An effort will be made to clarify those aspects sufficiently supported by evidence-based studies, and to underline those that remain unfounded.


title: Human coronavirus 229E infects polarized airway epithelia from the apical surface.

text: Gene transfer to differentiated airway epithelia with existing viral vectors is very inefficient when they are applied to the apical surface. This largely reflects the polarized distribution of receptors on the basolateral surface. To identify new receptor-ligand interactions that might be used to redirect vectors to the apical surface, we investigated the process of infection of airway epithelial cells by human coronavirus 229E (HCoV-229E), a common cause of respiratory tract infections. Using immunohistochemistry, we found the receptor for HCoV-229E (CD13 or aminopeptidase N) localized mainly to the apical surface of airway epithelia. When HCoV-229E was applied to the apical or basolateral surface of well-differentiated primary cultures of human airway epithelia, infection primarily occurred from the apical side. Similar results were noted when the virus was applied to cultured human tracheal explants. Newly synthesized virions were released mainly to the apical side. Thus, HCoV-229E preferentially infects human airway epithelia from the apical surface. The spike glycoprotein that mediates HCoV-229E binding and fusion to CD13 is a candidate for pseudotyping retroviral envelopes or modifying other viral vectors.


title: Transanal endoscopic microsurgery.

text: TEM has been used effectively to treat large rectal polyps and early rectal malignancy for more than 20 years in Europe. Until recently, only a few specialized centers offered TEM in the United States, where it is now gaining popularity. Many hospitals have purchased equipment and are offering TEM; however, the equipment is expensive and the learning curve is steep. Therefore, it is essential that anyone performing TEM have an adequate number of cases to develop and maintain expertise in this technique. That being said, TEM remains unique when compared with laparoscopy and other minimally invasive techniques that incorporate less invasive methods of performing old operations. TEM allows surgeons to perform operations that were impossible before the development and acceptance of this technique.


title: The polymerase gene of corona- and toroviruses: evidence for an evolutionary relationship.

text: In this paper we demonstrate that the organization of the polymerase gene of toroviruses and coronaviruses is similar. The polymerase gene of both virus families consists of at least two large ORFs (1a and 1b). Four domains of conserved amino acid sequences have been identified in nearly identical positions in the 3' ORF of the pol gene of toroviruses and coronaviruses. The most 3' conserved domain which is still unique for these viruses encodes a 33-kDA protein in MHV-A59, which is cleaved from a precursor protein. Expression of ORF1b of the pol gene of both virus families occurs by ribosomal frameshifting. A predicted stem-loop structure and pseudoknot are conserved in the ORF1a/ORF1b overlap of toro- and coronaviruses. On the basis of these results we postulate that toro- and coronaviruses are ancestrally more related to each other than to other families of positive stranded RNA viruses.


title: The protective role of cytotoxic T cells and interferon against coronavirus invasion of the brain.

text: MHV-A59 causes focal acute encephalitis, acute hepatitis, and chronic demyelination while MHV-2 causes acute hepatitis and no brain involvement. The difference in organ tropism between these two closely related MHVs is not related to the ability of these viruses to grow in brain cells since both viruses grow equally well in primary glial cell cultures derived from neonatal mouse brains. We postulated therefore that the ability of the virus to stimulate certain host immunological factors may be important for protection of the brain against invasion and replication of the virus. In this study we performed preliminary experiments to investigate the potential role of two host factors in protection of the brain against MHV invasion: cytotoxic T cells and interferon. Four week old beta 2M(-/-) mice, lacking beta 2 microglobulin, MHC class I expression and functional cytotoxic CD8+ T cells were inoculated intracerebrally (IC) with MHV-2 and analyzed at various intervals post infection for histopathology and viral titers in organs. Histology revealed both acute hepatitis and acute encephalitis. Acute encephalitis was observed in periventricular areas. Mononuclear lymphocytic infiltration involved the choroid plexus, the ependyma and in the surrounding brain parenchyma. There was no involvement of other areas of the brain including areas that are typically involved in A59 infection of C57B1/6 mice. By contrast, C57b1/6 mice infected with MHV-2 showed no involvement of the brain parenchyma and only slight inflammation of the choroid plexus was present. High titers of infectious virus was detected by plaque assay in both brains and livers of beta 2M(-/-) mice infected with MHV-2 in contrast to only liver titers in C57B1/6 mice infected with a similar dose of MHV-2.(ABSTRACT TRUNCATED)


title: Pathological study on 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 autopsies of probable SARS cases were studied by microscope, and the clinical data was reviewed. RESULTS The typical pathological changes of lungs were diffuse hemorrhaging on the surface. A combination of serous, fibrinous and hemorrhagic inflammation was seen in most of the pulmonary alveoli with the engorgement of capillaries and detection of micro-thrombosis in some of these capillaries. Pulmonary alveoli thickened with interstitial mononuclear inflammatory infiltrates, suffered diffuse alveolar damage, experienced desquamation of pneumocytes and had hyaline-membrane formation, fibrinoid materials, and erythrocytes in alveolar spaces. There were thromboembolisms in some bronchial arteries. Furthermore, hemorrhagic necrosis was also evident in lymph nodes and spleen with the attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and lesions having existed before hospitalization were observed in the liver, heart, kidney and pancreas. CONCLUSION Severe damage to the pulmonary and immunological systems is responsible for the clinical features of SARS and may lead to the death of patients.


title: Kinetics of severe acute respiratory syndrome (SARS) coronavirus-specific antibodies in 271 laboratory-confirmed cases of SARS.

text: The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G detected in 59% of samples collected within 14 days and persisting for 60 to 95 days after the onset of illness.


title: An electron microscopic study of experimentally-induced HEV encephalitis.

text: A gnobiotic piglet, was inoculated intracerebrally with hemagglutinating encephalomyelitis virus (strain VW572). Mononuclear cells formed vascular cuffs and were disseminated in the brain parenchyma. A few neurons were surrounded by the same kind of cells. Virus particles morphologically similar to coronavirus particles were found in the cytoplasm of both chromatolytic light neurons and hyperchromic dark neurons. The particles were in vesicles of distended endoplasmic reticulum and in the hypertrophied Golgi apparatus.


title: Mental health and mental illness in the workplace: diagnostic and treatment issues.

text: Mental health, mental illness and stress-related disability are especially ill-defined, complex and controversial issues when considered in the context of the workplace. A multi-determined disorder such as major depressive disorder (MDD) does not fit a simple cause and effect model, but is similar to other complex occupational illnesses such as low back pain. Currently, a knowledge gap exists between mental health professionals and employers regarding symptom-based models of illness and function-based models of work performance. As a result, psychiatric disorders affecting workers are under-identified and under-treated and likely result in unmitigated impairment and disability. The authors examine several conceptual models for workplace mental illness across medical and psychological disciplines and propose a unifying construct. The utility of the existing screening methods for common workplace illnesses and their potential application are reviewed. The challenges of diagnosis and effective treatment of workplace mental illness are highlighted within an "occupational mental health system" with suggestions for future research directions.


title: Trial surveillance of cases with acute respiratory symptoms at IMCJ Hospital.

text: We have developed a surveillance system that can detect a severe acute respiratory syndrome (SARS) outbreak in a hospital as quickly as possible using the "SARS alert" strategy proposed by the World Health Organization (WHO). Our research examined hospital staff and in-patients during the winter of 2003/2004. We defined patients with a fever of over 38 degrees C and respiratory symptoms as "cases with acute respiratory symptoms." During the study period, 215 such cases (78% in-patients; 22% hospital staff members) were reported. A rapid diagnostic test for influenza was performed on 131 individuals, with 52 having positive results. There were no cases fulfilling the definition of SARS provided by the WHO in their SARS alert. The present surveillance system will be of use in the early detection of a SARS epidemic in a hospital as well as in early detection of similar illnesses accompanied by acute respiratory symptoms, such as influenza.


title: Mechanical ventilation of SARS patients. Safety issues involving breathing-circuit filters.

text: Patients suffering from severe acute respiratory syndrome (SARS) sometimes require mechanical ventilation. This raises safety concerns about the SARS virus being carried by droplets that exit from the exhalation limb of the ventilator. ECRI recommends that breathing-circuit filters be incorporated in the exhalation limb of any ventilator used on a patient with SARS. In this article, we review the issues behind our recommendations and describe steps hospitals can take to prevent any adverse effects on ventilation.


title: Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans, and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The SARS-CoV receptor, human angiotensin 1-converting enzyme 2 (hACE2), was detected in ciliated airway epithelial cells of human airway tissues derived from nasal or tracheobronchial regions, suggesting that SARS-CoV may infect the proximal airways. To assess infectivity in an in vitro model of human ciliated airway epithelia (HAE) derived from nasal and tracheobronchial airway regions, we generated recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF7a/7b) and insertion of the green fluorescent protein (GFP), resulting in SARS-CoV GFP. SARS-CoV GFP replicated to titers similar to those of wild-type viruses in cell lines. SARS-CoV specifically infected HAE via the apical surface and replicated to titers of 10(7) PFU/ml by 48 h postinfection. Polyclonal antisera directed against hACE2 blocked virus infection and replication, suggesting that hACE2 is the primary receptor for SARS-CoV infection of HAE. SARS-CoV structural proteins and virions localized to ciliated epithelial cells. Infection was highly cytolytic, as infected ciliated cells were necrotic and shed over time onto the luminal surface of the epithelium. SARS-CoV GFP also replicated to a lesser extent in ciliated cell cultures derived from hamster or rhesus monkey airways. Efficient SARS-CoV infection of ciliated cells in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis.


title: Continued seasonal circulation of enterovirus D68 in the Netherlands, 2011-2014.

text: Enterovirus D68 (EV-D68) continued to circulate in a seasonal pattern in the Netherlands, after the outbreak in 2010. Outpatient EV-D68 cases, mainly in the under 20 and 50–59 years age groups, presented with relatively mild respiratory disease. Hospital-based enterovirus surveillance identified more severe cases, mainly in children under 10 years of age. Dutch partial VP1 genomic region sequences from 2012 through 2014 were distributed over three sublineages similar to EV-D68 from the outbreak in the US in 2014.


title: Severe acute respiratory syndrome-related psychiatric and posttraumatic morbidities and coping responses in medical staff within a primary health care setting in Singapore.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a major new infectious disease of this century that is unique in its high morbidity and concentration in health care settings. We aimed to determine the level of psychological impact and coping styles among the medical staff in a primary health care setting. METHOD Using a structured questionnaire, we conducted a cross-sectional survey of the doctors and nurses working within a public, primary health care setting in mid-July 2003. The main outcome measures were rates of psychiatric morbidity, level of posttraumatic stress symptoms, and coping strategies. RESULTS The response rate was 92.0%. Of the 277 respondents (91 doctors and 186 nurses), psychiatric morbidity and posttraumatic morbidity were found in 20.6% and 9.4%, respectively. Both psychiatric and posttraumatic morbidities were associated with higher scores on coping efforts including self-distraction, behavioral disengagement, social support, venting, planning, and self-blame (all p <.001), but not with direct exposure factors such as contact with suspected SARS patients or working in fever rooms/tentages. Multivariate analysis showed that psychiatric morbidity was associated with post-traumatic morbidity (p =.02) and denial (p =.03), whereas posttraumatic morbidity was associated with younger age (p =.007), being married (p =.02), psychiatric morbidity (p =.02), self-distraction (p =.02), behavioral disengagement (p =.01), religion (p =.003), less venting (p =.04), less humor (p =.04), and less acceptance (p =.02). CONCLUSION SARS-related psychiatric and posttraumatic morbidities were present in the medical staff within a primary health care setting. Specific coping efforts, age, and marital status, not direct exposure factors, were associated with psychological morbidity. These findings provide possible foci for early identification and psychological support.


The role of the Emergency Department: beyond gatekeeping.


title: Causes of mortality in reintroduced Eurasian lynx in Switzerland.

text: Seventy-two lynx, found dead in the Swiss Alps and the Jura Mountains (Switzerland) from 1987-99, were evaluated to determine the cause of death. Seventy-two per cent (52/72) of all animals died because of noninfectious diseases or causes such as vehicular collision and poaching. Eighteen percent (13/72) died from infectious diseases, including some which could have been transferred to the lynx from domestic animals or other wild animals such as panleukopenia and sarcoptic mange. If only radio-tagged animals (included in a monitoring program) were taken into consideration, the percentage of mortality caused by infectious diseases rose to 40%, indicating that infections might be underestimated in randomly found mortality events. We hypothesize that even a few cases of infections in a small population like the lynx, which are additionally threatened by noninfectious causes, may threaten the long term survival of the population.


title: Human metapneumovirus infection in young children hospitalized with respiratory tract disease.

text: BACKGROUND Human metapneumovirus (hMPV) is a newly recognized pathogen associated with respiratory tract disease (RTD). OBJECTIVES To evaluate the incidence of hMPV infection in children hospitalized with RTD and to analyze the virologic and clinical features of hMPV infection. STUDY DESIGN All children younger than 5 years of age hospitalized for RTD were included in this 1-year prospective study. hMPV was detected in nasopharyngeal secretions by reverse transcription polymerase chain reaction. The hMPV F gene amplification products were sequenced, and a phylogenetic tree was constructed. Samples were also tested for other respiratory viruses by both direct immunofluorescence assay and virus culture. RESULTS hMPV, detected in 50 of 589 (8.5%) children, represented the second leading cause of RTD after respiratory syncytial virus (RSV). Infections with hMPV occurred mainly between December and April. hMPV isolates clustered into the 4 subgroups (A1, A2, B1 and B2) currently recognized; the majority (72%) of hMPV isolates belonged to subgroup A1. Among the 35 children infected with hMPV alone, 23 (65.7%) had bronchiolitis, 5 (14.3%) had pneumonia, 2 (5.7%) had asthma exacerbation and 5 (14.3%) had a limited upper RTD. Fifteen (30%) of the hMPV-infected children were coinfected with RSV. As compared with children infected with hMPV or RSV alone, duration of hospitalization and requirement for supplemental oxygen were increased in the hMPV/RSV-coinfected children. CONCLUSIONS hMPV is a frequent cause of RTD in young children. hMPV/RSV coinfection is frequent and could be more severe than a single hMPV or RSV infection.


title: Patellar fractures in adults.

text: Patellar fracture is a common injury caused by excessive tension through the extensor mechanism or a direct blow. The intact patella increases the leverage and efficiency of the extensor mechanism and articulates with the femoral trochlea. Patellar fractures can lead to stiffness, extension weakness, and patellofemoral arthritis. Nonsurgical management is indicated for nondisplaced fractures with an intact extensor mechanism. Surgical fixation is recommended for fractures that either disrupt the extensor mechanism or demonstrate >2 to 3 mm step-off and >1 to 4 mm of displacement. Anatomic reduction and fixation with a tension-band technique is associated with the best outcomes; however, symptomatic hardware is a frequent complication. Open fractures are associated with more complications than closed fractures. These complications can be mitigated with timely débridement, irrigation, and internal fixation.


title: Potent inhibition of SARS-associated coronavirus (SCOV) infection and replication by type I interferons (IFN-alpha/beta) but not by type II interferon (IFN-gamma).

text: We sought to investigate the anti-severe acute respiratory syndrome (SARS)-associated coronavirus (SCoV) activities of type I (alpha and beta) and type II (gamma) interferons (IFN) in vitro. Type I IFNs protected cells from cytopathic effects (CPE) induced by SCoV, and inhibited viral genomic RNA replication in FRhk-4 cells (measured by quantitative RT-PCR) in a dose-dependent manner. Intracellular viral RNA copies were reduced 50% by IFN-alpha at a concentration of 25 U/ml and by IFN-beta at a concentration of 14 U/ml. IFN-gamma had fewer effects on inhibition of viral infection and replication. The type I IFN receptor signaling pathway in host cells is mainly involved in the inhibition of SCoV infection and replication. Type I IFNs could be used as potential agents for anti-SARS treatment.


title: Baculovirus surface display of SARS coronavirus (SARS-CoV) spike protein and immunogenicity of the displayed protein in mice models.

text: The baculovirus surface display technique has provided an ideal tool to display foreign proteins with natural conformation, functions, and immunogenicity. In this work, we explored the application of this technique on SARS-associated coronavirus (SARS-CoV) spike (S) protein, and further analyzed the immunogenicity of displayed S protein. The entire ectodomain of S protein was fused between the gp64 signal peptide and the VSV-G membrane anchor and successfully displayed on the baculovirus surface. Subcutaneous injection with purified S-displayed baculoviruses without adjuvant elicited highly effective production of specific and neutralizing antibodies against S protein in mice. These results confirmed a successful surface display of S protein on baculoviruse, and suggested a potential role of S-displayed baculoviruses as a novel live virus-based vaccine candidate for SARS-CoV.


SARS: a local public health perspective.


title: Knowledge and practices among the general practitioners of Karachi regarding dog bite management.

text: OBJECTIVE To find out the knowledge and practices among the general practitioners (GPs) of Karachi regarding dog bite management. METHODS This cross sectional study was carried out in private and public Qlinics of Karachi using a pre-tested self-administered questionnaire. The study population was composed of 151 GPs with MBBS degree. Data was analyzed on SPSS version 12.0. RESULTS Out of total 151 general practitioners, 124 were male and 27/female doctors. The majority (77.5%) of GPs knew the cause of rabies, but only 51.7% knew about the incubation period. Only 19.4% GPs had appropriate knowledge about the first line treatment. Almost all GPs (98%) had no knowledge about the types of anti-rabies vaccine and only 19.2% knew about anti-rabies serum. CONCLUSION There is an apparent lack of awareness among GPs regarding appropriate animal wound management and vaccine administration. Reorientation programmes and continued medical education (CME) for GPs are required to highlight WHO guidelines regarding treatment of animal bite.


title: Contributions of the viral genetic background and a single amino acid substitution in an immunodominant CD8+ T-cell epitope to murine coronavirus neurovirulence.

text: The immunodominant CD8+ T-cell epitope of a highly neurovirulent strain of mouse hepatitis virus (MHV), JHM, is thought to be essential for protection against virus persistence within the central nervous system. To test whether abrogation of this H-2Db-restricted epitope, located within the spike glycoprotein at residues S510 to 518 (S510), resulted in delayed virus clearance and/or virus persistence we selected isogenic recombinants which express either the wild-type JHM spike protein (RJHM) or spike containing the N514S mutation (RJHM(N514S)), which abrogates the response to S510. In contrast to observations in suckling mice in which viruses encoding inactivating mutations within the S510 epitope (epitope escape mutants) were associated with persistent virus and increased neurovirulence (Pewe et al., J Virol. 72:5912-5918, 1998), RJHM(N514S) was not more virulent than the parental, RJHM, in 4-week-old C57BL/6 (H-2b) mice after intracranial injection. Recombinant viruses expressing the JHM spike, wild type or encoding the N514S substitution, were also selected in which background genes were derived from the neuroattenuated A59 strain of MHV. Whereas recombinants expressing the wild-type JHM spike (SJHM/RA59) were highly neurovirulent, A59 recombinants containing the N514S mutation (SJHM(N514S)/RA59) were attenuated, replicated less efficiently, and exhibited reduced virus spread in the brain at 5 days postinfection (peak of infectious virus titers in the central nervous system) compared to parental virus encoding wild-type spike. Virulence assays in BALB/c mice (H-2d), which do not recognize the S510 epitope, revealed that attenuation of the epitope escape mutants was not due to the loss of a pathogenic immune response directed against the S510 epitope. Thus, an intact immunodominant S510 epitope is not essential for virus clearance from the CNS, the S510 inactivating mutation results in decreased virulence in weanling mice but not in suckling mice, suggesting that specific host conditions are required for epitope escape mutants to display increased virulence, and the N514S mutation causes increased attenuation in the context of A59 background genes, demonstrating that genes other than that for the spike are also important in determining neurovirulence.


title: Inhibition of anthrax protective antigen outside and inside the cell.

text: In the course of Bacillus anthracis infection, B. anthracis lethal factor (LF) and edema factor bind to a protective antigen (PA) associated with cellular receptors ANTXR1 (TEM8) or ANTXR2 (CMG2), followed by internalization of the complex via receptor-mediated endocytosis. A new group of potential antianthrax drugs, beta-cyclodextrins, has recently been described. A member of this group, per-6-(3-aminopropylthio)-beta-cyclodextrin (AmPrbetaCD), was shown to inhibit the toxicity of LF in vitro and in vivo. In order to determine which steps in lethal factor trafficking are inhibited by AmPrbetaCD, we developed two targeted fluorescent tracers based on LFn, a catalytically inactive fragment of LF: (i) LFn site specifically labeled with the fluorescent dye AlexaFluor-594 (LFn-Al), and (ii) LFn-decorated liposomes loaded with the fluorescent dye 8-hydroxypyrene-1,3,6-trisulfonic acid (LFn-Lip). Both tracers retained high affinity to PA/ANTXR complexes and were readily internalized via receptor-mediated endocytosis. Using fluorescent microscopy, we found that AmPrbetaCD inhibits receptor-mediated cell uptake but not the binding of LFn-Al to PA/ANTXR complexes, suggesting that AmPrbetaCD works outside the cell. Moreover, AmPrbetaCD and LFn-Al synergistically protect RAW 264.7 cells from PA-mediated LF toxicity, confirming that AmPrbetaCD did not affect the binding of LFn-Al to receptor-associated PA. In contrast, AmPrbetaCD did not inhibit PA-mediated internalization of LFn-Lip, suggesting that multiplexing of LFn on the liposomal surface overcomes the inhibiting effects of AmPrbetaCD. Notably, internalized LFn-Al and LFn-Lip protected cells that overexpressed anthrax receptor TEM8 from PA-induced, LF-independent toxicity, suggesting an independent mechanism for PA inhibition inside the cell. These data suggest the potential for the use of beta-cyclodextrins in combination with LFn-Lip loaded with antianthrax drugs against intracellular targets.


Background paper. On the role of the immune response in the course of coronavirus JHM-induced encephalomyelitides in mice and rats.


title: Increasing importance of viruses in acute otitis media.

text: Acute otitis media is generally considered a simple bacterial infection that can be effectively treated with antibiotics. However, despite the extensive use of broad-spectrum antibiotics, poor clinical response to treatment of acute otitis media is common in children. Numerous studies ranging from animal experiments to extensive clinical studies have clearly demonstrated that respiratory viruses play a crucial role in the aetiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory tract initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. Respiratory viruses induce a release of inflammatory mediators in the nasopharynx, increase bacterial colonization and adherence, and have a suppressive effect on the host's immune defense. Recent data indicate that at least some types of viruses actively invade the middle ear. Viruses also seem to enhance the inflammatory process in the middle ear and impair the outcome of the disease. Vaccines against the major viruses predisposing to acute otitis media hold a great promise for the prevention of this disease. Major advances in the management of acute otitis media will require further research into the mechanisms of viral infection, viral-bacterial interaction and the host inflammatory response during viral infection.


title: Potential cross-reactivity of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) nucleocapsid (N)-based IgG ELISA assay for plasma samples from HIV-1 positive intravenous drug users (IDUs).

text: AIM to evaluate the specificity of the SARS-CoV N protein-based IgG ELISA assay for detection of immunoglobulin G (IgG) in plasma samples obtained from HIV-1 positive and HIV-1 negative intravenous drug users (IDUs). METHODS the SARS-CoV N gene was cloned into pQE-80L vector, and the constructs were transformed into Escherichia coli BL21. The 6x His-tagged N protein was expressed by inducing the bacterial cells with isopropyl-1-thio-D-galactopyranoside (IPTG) and purified by Ni-NTA affinity resin. The 6x His-tagged N protein was used as antigen for ELISA assay and evaluated for the serum samples from patients with SARS positive and the plasma samples from the HIV-1 positive and negative IDUs. RESULTS all sera samples from patients with SARS positive were the ELISA positive (100% sensitivity). The ELISA assay yielded no positive results of the total 61 HIV-1 negative IDU samples (100% specificity) and two positive results of the total 68 HIV-1 positive IDU samples (97.06% specificity). CONCLUSION the specificity of the SARS-CoV N protein-based IgG ELISA assay for the detection of the SARS-CoV N specific IgG in plasma samples from IDUs with HIV-1 positive is, therefore, questionable.


Early Guidelines in the COVID-19 Pandemic.


title: Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing.

text: Wound healing is an intricate process that requires complex coordination between many cell types and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care, the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds, including excessive inflammation, ischemia, scarring, and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or are currently used in clinical practice.


title: Generation of synthetic severe acute respiratory syndrome coronavirus pseudoparticles: implications for assembly and vaccine production.

text: The recently emerged severe acute respiratory syndrome coronavirus (SARS-CoV) contains four structural genes, two replicase-transcriptase open reading frames, and more than five potential genes of unknown function. Despite this relative simplicity, the molecular regulation of SARS-CoV replication and assembly is not understood. Here, we report that two viral genes, encoding the SARS-CoV membrane (M) and nucleocapsid (N) proteins, are necessary and sufficient for formation of virus-like particles. Expression vectors encoding these two proteins were synthesized by using preferred human codons. When M and N expression plasmids were cotransfected into human 293 renal epithelial cells, pseudoparticles formed readily. The addition of a third gene, encoding the spike (S) glycoprotein, facilitated budding of particles that contained a corona-like halo resembling SARS-CoV when examined by transmission electron microscopy, with a buoyant density characteristic of coronaviruses. Specific biochemical interactions of these proteins were also shown in vitro. The S, M, and N proteins of the SARS-CoV are, therefore, necessary and sufficient for pseudovirus assembly. These findings advance the understanding of the morphogenesis of SARS-CoV and enable the generation of safe, conformational mimetics of the SARS virus that may facilitate the development of vaccines and antiviral drugs.


title: Genomic classification using an information-based similarity index: application to the SARS coronavirus.

text: Measures of genetic distance based on alignment methods are confined to studying sequences that are conserved and identifiable in all organisms under study. A number of alignment-free techniques based on either statistical linguistics or information theory have been developed to overcome the limitations of alignment methods. We present a novel alignment-free approach to measuring the similarity among genetic sequences that incorporates elements from both word rank order-frequency statistics and information theory. We first validate this method on the human influenza A viral genomes as well as on the human mitochondrial DNA database. We then apply the method to study the origin of the SARS coronavirus. We find that the majority of the SARS genome is most closely related to group 1 coronaviruses, with smaller regions of matches to sequences from groups 2 and 3. The information based similarity index provides a new tool to measure the similarity between datasets based on their information content and may have a wide range of applications in the large-scale analysis of genomic databases.


title: Interferon-alpha-producing cells are localized in gut-associated lymphoid tissues in transmissible gastroenteritis virus (TGEV) infected piglets.

text: Transmissible gastroenteritis virus (TGEV) infection of piglets results in a very rapid and massive release of IFN-alpha in serum and secretions. The objective of this work was to characterize the IFN-alpha-producing cells (IPC) in tissues of TGEV-infected piglets. Caesarean-derived colostrum-deprived piglets were infected orally with the TGEV virulent Miller strain and IPC were characterized in situ by immunohistochemistry, using a rabbit anti-pig IFN-alpha antiserum. IPC were almost exclusively detected in intestinal tissues and mesenteric lymph nodes (MLN), as early as 6 h post inoculation (p.i.), with a peak at 12-18 h. They disappeared by 24 h. IPC were localized between enterocytes in the small intestine epithelial layer, in the lamina propria, around the Peyer's patches and, at highest frequency, in MLN. Very few IPC were present in the spleen and popliteal lymph nodes of infected piglets. Double immunohistochemical staining for IFN-alpha and leukocyte markers on MLN cryosections showed that IPC were mainly Swine Leukocyte Antigen (SLA) class II positive, and were not stained by an anti-macrophage (SWC3a) MAb. In addition, double staining with anti-TGEV and anti-IFN-alpha MAbs showed that viral antigens were present in MLN, close to IPC. These results show for the first time the presence of IPC in gut mucosa and gut-associated lymphoid tissues in response to an enteropathogenic virus. Moreover, this work shows that IFN-alpha released in serum is likely to originate almost exclusively from gut IPC triggered locally by viral antigens to produce IFN-alpha, since there were very few IPC in spleen or peripheral lymph nodes. MHC class II molecule expression by gut-associated IPC suggests that these cells may be the in vivo mucosal counterparts of the dendritic cells recently shown to produce IFN-alpha after in vitro viral induction.


title: Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism.

text: PURPOSE Physiological uptake in the uncinate process or pancreatic head has been described with Ga-labeled PET tracers for somatostatin receptor imaging. In-DTPA-octreotide is the only registered radiopharmaceutical for the imaging of neuroendocrine tumors. We studied the uptake in this region of the pancreatic head on somatostatin receptor scintigraphy (SRS) using In-DTPA-octreotide in a large group of patients. Furthermore, known physiological and clinical characteristics are discussed in an attempt to elucidate this phenomenon. METHODS Four hundred seven patients underwent SRS using In-DTPA-octreotide in our department in 2014. After excluding patients with a known malignancy in or close to the pancreas, as well as all scans without SPECT/CT of the upper abdomen, we reviewed 178 scans in total. The uptake was graded on a 4-point scale that correlates the uptake in the pancreatic head to physiological uptake in the liver. RESULTS Uptake in the region of the pancreatic head, including the uncinate process, was seen in 46 (26%) of 178 patients on SPECT/CT and in 12 patients (7%) on planar imaging. On SPECT/CT, uptake was lower than the liver in 26 patients (15%), equal to the liver in 17 patients (10%), and higher than the liver in 3 patients (2%). In patients with diabetes mellitus (DM), the incidence of uptake in the pancreatic head was 50% on SPECT/CT. CONCLUSIONS Physiological uptake in the pancreatic head is seen on SPECT/CT with In-DTPA-octreotide in 26% of patients, and the incidence is doubled in patients with DM. Previous case reports showed uptake in the pancreatic head due to histologically proven pancreatic polypeptide (PP) cell hyperplasia. Also, patients with DM have elevated serum PP concentrations, which is likely due to PP cell hyperplasia. Because 90% of PP cells are present in the pancreatic head, PP cell hyperplasia is the most likely explanation for visualization of the pancreatic head on SRS in a substantial number of patients.


title: Use of antibiotics in a haematology ward--an audit.

text: INTRODUCTION Rising rates of antibiotic resistance prompted a review of antibiotic use policies hospitalwide. The Department of Haematology established a new set of consensus guidelines in 2002 for antibiotic use in febrile neutropenia. The aim of our study was to audit adherence to the guidelines established for febrile neutropenia in patients treated for haematologic malignancies. MATERIALS AND METHODS An antibiotic escalation pathway was developed by haematologists and infectious disease physicians. Adherence to the guidelines was audited. Patients with acute myeloid leukaemia (AML) or acute lymphocytic leukaemia (ALL) who had febrile neutropenia after chemotherapy were reviewed. The audit was performed by a retrospective review of casenotes. RESULTS Forty patients with 100 episodes of febrile neutropenia were surveyed. Thirty-two had AML, 7 had ALL and 1 had undifferentiated leukaemia. In 76% of episodes, fever developed within the first 14 days of neutropenia. In 31 episodes, cefepime was started as the first-line agent; hence, compliance with the first-line agent was 31%. Fever defervesced in 13 episodes. The most common reason for switching antibiotics was persistent fever. There were clinical indications for non-compliance with the use of the first-line agent in all cases. There were 3 deaths - none related to non-compliance with or strict adherence to the guidelines. Four patients had proven fungal infections. CONCLUSIONS Given the complex nature of the cases, compliance was reasonable, as there were valid reasons in all cases where the guidelines were not adhered to. Based on our findings, the guidelines could be simplified.


Ultraviolet Germicidal Irradiation to Decontaminate Filtering Face Piece Respirators During COVID-19 Pandemic.


title: Quality of life, psychological and physiological changes following exercise training in patients with chronic heart failure.

text: OBJECTIVE To assess the physiological and psychosocial effects of exercise training in chronic heart failure. SUBJECTS/PATIENTS Twenty-six men with heart failure (New York Heart Association functional classes II and III) aged 52.5 (SD 9.8) years, were studied. METHODS The subjects were randomized either to rehabilitation group (Group A: 16 patients), participating in a 6-month exercise training program, or to control group (Group B: 10 patients). A psychosocial assessment, which included affective (Beck Depression Inventory and Hospital Anxiety and Depression Scale), quality of life (Quality of Life Index, Minnesota Living with Heart Failure Questionnaire and the Scale of Life Satisfaction) and personality (Eysenck Personality Questionnaire) parameters, was performed at the beginning and the end of the study. RESULTS After training VO2 peak increased by 36% and exercise time by 35%, p < 0.05. A significant decrease in anxiety and depression was also observed. Moreover, trained patients demonstrated a significant improvement in quality of life. No significant correlations were found between deltaVO2 peak and all psychosocial parameter gains. However, the more depressed patients showed the largest physiological responses. CONCLUSION An exercise rehabilitation program in patients with chronic heart failure is useful for improving their work capacity and psychosocial status. Improvements in psychological status seem to be independent of the aerobic gains.


title: Impaired T cell immunity in B cell-deficient mice following viral central nervous system infection.

text: CD8(+) T cells are required to control acute viral replication in the CNS following infection with neurotropic coronavirus. By contrast, studies in B cell-deficient (muMT) mice revealed Abs as key effectors in suppressing virus recrudescence. The apparent loss of initial T cell-mediated immune control in the absence of B cells was investigated by comparing T cell populations in CNS mononuclear cells from infected muMT and wild-type mice. Following viral recrudescence in muMT mice, total CD8(+) T cell numbers were similar to those of wild-type mice that had cleared infectious virus; however, virus-specific T cells were reduced at least 3-fold by class I tetramer and IFN-gamma ELISPOT analysis. Although overall T cell recruitment into the CNS of muMT mice was not impaired, discrepancies in frequencies of virus-specific CD8(+) T cells were most severe during acute infection. Impaired ex vivo cytolytic activity of muMT CNS mononuclear cells, concomitant with reduced frequencies, implicated IFN-gamma as the primary anti viral factor early in infection. Reduced virus-specific CD8(+) T cell responses in the CNS coincided with poor peripheral expansion and diminished CD4(+) T cell help. Thus, in addition to the lack of Ab, limited CD8(+) and CD4(+) T cell responses in muMT mice contribute to the ultimate loss of control of CNS infection. Using a model of virus infection restricted to the CNS, the results provide novel evidence for a role of B cells in regulating T cell expansion and differentiation into effector cells.


Respiratory support for severe acute respiratory syndrome: integration of efficacy and safety.


title: Cutaneous vasculitis update: neutrophilic muscular vessel and eosinophilic, granulomatous, and lymphocytic vasculitis syndromes.

text: Most biopsies of cutaneous vasculitis will exhibit a small vessel neutrophilic vasculitis [leukocytoclastic vasculitis (LCV)] that is associated with immune complexes on direct immunofluorescence examination or, less commonly, antineutrophilic cytoplasmic antibodies (ANCA) by indirect immunofluorescence testing. Is in uncommon for skin biopsy to reveal solely a neutrophilic arteritis signifying the presence of cutaneous polyarteritis nodosa or, if accompanied by significant lobular panniculitis, nodular vasculitis/erythema induratum. In other cases, cutaneous vascular damage (fibrinoid necrosis, muscular vessel wall disruption, or endarteritis obliterans) will be mediated by a nonneutrophilic inflammatory infiltrate. Eosinophilic vasculitis can be a primary (idiopathic) process that overlaps with hypereosinophilic syndrome, or it can be a secondary vasculitis associated with connective tissue disease or parasite infestation. Authentic cutaneous granulomatous vasculitis (versus vasculitis with extravascular granulomas) can represent a cutaneous manifestation of giant cell arteritis, an eruption secondary to systemic disease such as Crohn's disease or sarcoidosis, or a localized disorder, often a post-herpes zoster (HZ) phenomenon. Lymphocytic vasculitis is a histologic reaction pattern that correlates with broad clinical differential diagnosis, which includes connective tissue disease - mostly systemic lupus erythematosus (SLE), endothelial infection by Rickettsia and viruses, idiopathic lichenoid dermatoses such as perniosis or ulcerative necrotic Mucha-Habermann disease, and angiocentric cutaneous T-cell lymphomas. Skin biopsy extending into the subcutis, identifying the dominant inflammatory cell and caliber of vessels affected, extravascular histologic clues such as presence of lichenoid dermatitis or panniculitis, and correlation with clinical data allows for accurate diagnosis of these uncommon vasculitic entities.


title: Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division.

text: The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G(2)/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.


title: Global monitoring of influenza: potential contribution of national networks from a French perspective.

text: The aim of global monitoring of influenza is to help decision making in regular seasonal influenza and in the case of a new pandemic. FluNet is the main tool for information sharing among the WHO Global Influenza Surveillance Network, as well as the public. It allows 112 WHO National Influenza Centers in 83 countries access to remote data entry. Weekly information on recent isolates and epidemiological situations are available to the public through many functionalities, for example, maps (animated or static), charts and raw data are embedded in the system for data display. Thus far, FluNet has collected weekly influenza surveillance data from up to 1997. A major outcome of this global network is the influenza vaccine composition, which is proposed twice a year (i.e., for both hemispheres) on the basis of the collected data. However, FluNet is far from performing comprehensive monitoring of influenza at a global level; 109 WHO member states still do not participate in the network and participating national influenza centers have only limited resources, which do not allow them to implement a reliable, accurate and real-time epidemiology of influenza in the areas they deserve. By following the time and space dynamics of an influenza strain, an epidemiologically valid system would make assessment of decisions after adopting preventive measures (e.g., closing schools, travel restriction, use of antivirals or of protective masks and mass immunization) possible. This international cooperation in public health fields must be considerably reinforced in the future, and should encourage database linkage with environmental information, allowing for the evaluation of the role of climate change, animal behavior or pollution involvement in disease.


title: Nurses' perceptions of severe acute respiratory syndrome: relationship between commitment and intention to leave nursing.

text: AIMS This paper reports a study which aimed to: (1) investigate the relationship between nurses' commitment to the nursing profession and organization and their intention to leave; (2) investigate nurses' perceptions of the possibility of acquiring severe acute respiratory syndrome infection and its moderation of their commitment to the nursing profession and the organization and their consequent intentions to leave the profession and the organization following the severe acute respiratory syndrome outbreak. BACKGROUND The outbreak of severe acute respiratory syndrome in 2003 resulted in a fatality rate of approximately 11%. Nurses in hospitals caring for patients with severe acute respiratory syndrome maintained close contact with the infected patients. The high risk of infection and death associated with caring for patients with severe acute respiratory syndrome had a great impact on nurse retention in hospitals. Nurse turnover in many countries where these outbreaks occurred has been high since the first outbreak occurred in March 2003. METHODS Three hundred and thirty nurses working at a Taiwan hospital during the time of the severe acute respiratory syndrome outbreak completed the Meyer, Allen & Smith Organizational and Occupational Commitment Scales, Intention to Leave and Perceived Stress of Infection Scales between July and August 2003. RESULTS All three components of occupational and organizational commitments were negatively associated with nurses' intentions to leave the nursing profession and the organization. Nurses' perceptions of the possibility of acquiring severe acute respiratory syndrome infection through caring for these patients had a moderating effect on the relationship between commitment and the intention to leave. CONCLUSIONS Perceived risk to life from infection has a possible influence on the commitment/intention-to-leave model in hospital nurses caring for patients with severe acute respiratory syndrome, and this information can inform hospital and nursing managers about nurse retention following a severe acute respiratory syndrome outbreak and the management of commitment in the context of nursing human resources management.


title: Minimally invasive splenectomy: an update and review.

text: Laparoscopic splenectomy (LS) has become an established standard of care in the management of surgical diseases of the spleen. The present article is an update and review of current procedures and controversies regarding minimally invasive splenectomy. We review the indications and contraindications for LS as well as preoperative considerations. An individual assessment of the procedures and outcomes of multiport laparoscopic splenectomy, hand-assisted laparoscopic splenectomy, robotic splenectomy, natural orifice transluminal endoscopic splenectomy and single-port splenectomy is included. Furthermore, this review examines postoperative considerations after LS, including the postoperative course of uncomplicated patients, postoperative portal vein thrombosis, infections and malignancy.


Will the severe acute respiratory syndrome epidemic recur?


title: High-resolution CT findings of severe acute respiratory syndrome at presentation and after admission.

text: OBJECTIVE The aim of this study was to assess the high-resolution CT (HRCT) findings at presentation and after hospital admission in patients with severe acute respiratory syndrome (SARS). MATERIALS AND METHODS We reviewed the HRCT findings at presentation (n = 12) and after hospital admission (n = 25) of 29 patients with SARS and compared the HRCT findings with the radiographic findings. HRCT scans were obtained using 1-mm (n = 28) or 2-mm (n = 1) collimation. The radiographs and HRCT scans were reviewed independently by two observers who reached a decision by consensus. RESULTS All patients had abnormal findings on HRCT at presentation. Eight of these 12 patients had normal findings on radiographs. The predominant HRCT findings at presentation consisted of unilateral (n = 6) or bilateral (n = 2) ground-glass opacities or focal unilateral (n = 2) or bilateral (n = 2) areas of consolidation. All patients showed progression of disease on follow-up. The predominant HRCT findings on follow-up CT scans consisted of unilateral (n = 2) or bilateral ground-glass opacities (n = 13), unilateral (n = 2) or bilateral consolidation (n = 5), or a mixed bilateral pattern of ground-glass attenuation, consolidation, and reticulation (n = 3). Reticulation with associated architectural distortion and mild traction bronchiectasis was present in eight patients. CONCLUSION HRCT can show parenchymal abnormalities in patients with SARS who have normal findings on radiographs at presentation. Follow-up CT scans obtained in hospitalized patients show findings consistent with fibrosis in a small percentage of patients.