title: Is There a Relationship between Pressure Gradients through Contemporary Oxygenators and Immune Cell Proliferation during Cardiopulmonary Bypass? A Pilot Study.

text: There have been many advances in the perfusion equipment used for cardiopulmonary bypass (CPB) surgery. A key component, the membrane oxygenator, has had a number of modifications in recent years and a recent clinical evaluation demonstrated disparity in various aspects of device performance. One difference among oxygenators, which to-date has received little attention, was the impact on the patient's immune cells, with some oxygenators producing a significantly greater increase in immune cell numbers after cross clamp. Such increases in immune cell proliferation may contribute to the development of a systemic inflammatory response (SIR), which has been demonstrated to have a negative impact on patient outcomes. Although factors contributing to immune cell proliferation during CPB are recognized to be multi-factorial, the goal of the current communication was to perform an ad hoc analysis of these raw data for evidence that pressure gradients through an oxygenator contributes to this outcome. Despite the observation that higher-pressure gradient oxygenators appeared to associate with increased immune cell proliferation, no correlation was detected in this analysis. This finding, however, provides further evidence for the complex nature of inflammation during CPB, which deserves ongoing discussion and investigation.


title: Sites of replication of a porcine respiratory coronavirus in 5-week-old pigs with or without maternal antibodies.

text: On farms, where the porcine respiratory coronavirus (PRCV) is enzootic, pigs usually become infected between 5 and 10 weeks of age while losing their maternal antibodies. It was examined whether PRCV replicates in the small intestine in such pigs. This point is important since intestinal replication with PRCV might induce immunity against TGEV not only by stimulating mucosal intestinal immunity, but also by the induction of a lactogenic IgA response at later age via the gut-mammary link. Five week old pigs with and without maternal antibodies were inoculated by aerosol or directly into the intestinal lumen. In aerosol inoculated pigs, virus replication was observed to high titres in the respiratory tract. Replication occurred in epithelial cells of nasal mucosa, trachea, bronchi bronchioli and alveoli and in alveolar macrophages. Small amounts of virus produced in the respiratory tract were ingested, but no intestinal replication of PRCV was demonstrated. Differences were not observed in virus titre and sites of replication in seronegative pigs compared to those in pigs with maternal antibodies. Upon inoculation of 10(5) or 10(7) TCID50 directly into the lumen of the cranial jejunum, no intestinal replication could be demonstrated.


title: A comparative study of the cellular uptake and photodynamic efficacy of three novel zinc phthalocyanines of differing charge.

text: Three novel substituted zinc (II) phthalocyanines (one anionic, one cationic and one neutral) were compared to two clinically used photosensitizers, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) and polyhematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Using the RIF-1 cell line, photodynamic efficacy was shown to be related to cellular uptake. The cationic phthalocyanine (PPC, pyridinium zinc [II] phthalocyanine) had improved activity over the other two phthalocyanines and slightly improved activity over PHP and m-THPC. The initial subcellular localization of each photosensitizer was dependent upon the hydrophobicity and plasma protein binding. The phthalocyanines had a punctate distribution indicative of lysosomes, whereas m-THPC and PHP had a more diffuse cytoplasmic localization. A relocalization of phthalocyanine fluorescence was observed in some cases following low-level light exposure, and this was charge dependent. The anionic phthalocyanine (TGly, tetraglycine zinc [II] phthalocyanine) relocalized to the nuclear area, the localization of the hydrophobic phthalocyanine (TDOPc, tetradioctylamine zinc [II] phthalocyanine) was unchanged, whereas the distribution of the cationic phthalocyanine (PPC) became more cytoplasmic. This suggests that relocalization following low-level irradiation is a critical factor governing efficacy, and a diffuse cytoplasmic distribution may be a determinant of good photodynamic activity.


title: Contrast-Induced Encephalopathy after Percutaneous Coronary Intervention.

text: UNLABELLED Contrast-induced encephalopathy (CIE) is a rare complication that presents with transient neurologic deficits and is caused by neurotoxicity of intravascular contrast media. The prognosis can be extremely favorable even in comatose patients. We reported a 76-year-old woman admitted for scheduled coronary angiography. The total amount of Optiray contrast media used was 150 mL. Immediately after the procedure, the patient developed consciousness disturbance, global aphasia, cortical blindness and right-sided weakness. CIE was diagnosed by computed tomography and subsequent magnetic resonance imaging. The patient recovered completely within 48 hours without any neurological deficits. KEY WORDS Angioplasty; Contrast-induced encephalopathy; Percutaneous coronary intervention.


title: Effect of magnetic resonance imaging on core body temperature in anaesthetised children.

text: Children undergoing magnetic resonance imaging (MRI) often require general anaesthesia (GA). Children under GA are at risk of decreases in body temperature. This risk may be greater during MRI due to MRI scanners requiring cool ambient temperatures. Conversely, radiofrequency radiation emitted by MRI scanners is absorbed by the patient as heat energy, creating a risk of an increase in body temperature. The aim of this study was to determine the proportion of anaesthetised children undergoing an MRI scan who develop hyperthermia or hypothermia, and the risk factors associated with temperature changes in these children. Pre-scan and post-scan tympanic temperatures were obtained from 193 children (aged three months to six years) undergoing an MRI procedure under GA. No active warming or cooling devices were used during the MRI scans. The median duration for anaesthesia was 42 minutes (35 to 57 minutes). Fifty-two percent of children were hypothermic after their scan, while no subjects were hyperthermic after their scan. The mean (± standard deviation) pre-scan temperature was 36.2°C±0.5°C, and the mean (± standard deviation) post-scan temperature was 35.9°C±0.6°C (an overall mean temperature decrease of 0.28°C was observed [95% confidence interval, -0.36°C to -0.19°C], P <0.001). In conclusion, core body temperature was found to decrease slightly during an MRI scan under GA. These results suggest that more focus is needed regarding the cooling effects of GA agents during MRI, as opposed to the heating effects of the MRI scanner.


title: Influenza- and respiratory syncytial virus-associated mortality and hospitalisations.

text: The aim of the current study was to estimate influenza- and respiratory syncytial virus (RSV)-associated mortality and hospitalisations, especially the influenza-associated burden among low-risk individuals < or =65 yrs old, not yet recommended for influenza vaccination in many European countries. Retrospectively during 1997-2003, Dutch national all-cause mortality and hospital discharge figures and virus surveillance data were used to estimate annual average influenza- and RSV-associated excess mortality and hospitalisation using rate difference methods. Influenza virus active periods were significantly associated with excess mortality among 50-64-yr-olds and the elderly, but not in younger age categories. Influenza-associated hospitalisation was highest and about equal for 0-1-yr-olds and the elderly, and also significant for low-risk adults. Hospitalisation among children was mostly due to respiratory conditions, and among adults cardiovascular complications were frequent. RSV-active periods were associated with excess mortality and hospitalisation among the elderly. The highest RSV-related excess hospitalisation was found in 0-1-yr-olds. Influenza-associated mortality was demonstrated in 50-64-yr-olds. Among low-risk individuals < or =65 yrs of age, influenza-associated hospitalisation rates were highest for 0-4-yr-olds, but also significant for 5-64-yr-olds. These data may further support extension of recommendations for influenza vaccination to include younger low-risk persons. The respiratory syncytial virus-associated burden was highest for young children but also substantial for the elderly.


title: Human neutralizing Fab molecules against severe acute respiratory syndrome coronavirus generated by phage display.

text: Human recombinant Fab fragments specific for the spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV) were screened from a human Fab library, which was generated from RNAs from peripheral lymphocytes of convalescent SARS patients. Among 50 randomly picked clones, 12 Fabs specially reacted with S protein by an enzyme-linked immunosorbent assay. The microneutralizing test showed that one clone, designated M1A, had neutralizing activity on Vero E6 cells against SARS-CoV. DNA sequence analysis indicated that the light- and heavy-chain genes of M1A Fab belong to the kappa2a and 4f families, respectively. A neutralizing test on purified M1A demonstrated that 0.5 mg/ml of M1A completely inhibited SARS-CoV activity, with an absence of cytopathic effect for 7 days. Real-time fluorescence reverse transcription-PCR also proved the neutralizing capacity of M1A. These data showed that the number of virus copies was significantly reduced in the M1A-treated group, suggesting an important role for M1A in passive immunoprophylaxis against the SARS virus.


title: The nucleocapsid protein gene of bovine coronavirus is bicistronic.

text: For animal RNA viruses that replicate through an RNA intermediate, reported examples of bicistronic mRNAs with overlapping open reading frames in which one cistron is contained entirely within another have been made only for those with negative-strand or double-stranded genomes. In this report, we demonstrate for the positive-strand bovine coronavirus that an overlapping open reading frame potentially encoding a 23-kDa protein (names the I [for internal open reading frame] protein) and lying entirely within the gene for the 49-kDa nucleocapsid phosphoprotein is expressed during virus replication from a single species of unedited mRNA. The I protein was specifically immunoprecipitated from virus-infected cells with an I-specific antipeptide serum and was shown to be membrane associated. Many features of I protein synthesis conform to the leaky ribosomal scanning model for regulation of translation. This, to our knowledge, is the first example of a bicistronic mRNA for a cytoplasmically replicating, positive-strand animal RNA virus in which one cistron entirely overlaps another.


title: Surveillance of community-acquired viral infections due to respiratory viruses in Rhone-Alpes (France) during winter 1994 to 1995.

text: Nasal swab from patients with acute flu-like illness were evaluated for the presence of respiratory viruses in the Rhone-Alpes region of France from 1 October 1994 through 2 May 1995. The relative frequencies and seasonal distributions of the specific viruses were assessed. In addition, virus type was correlated with specific clinical signs and symptoms. During the study, 962 samples were collected by 75 medical practitioners participating in the Groupe Regional d'Observation de la Grippe surveillance network. One or more viruses were detected from 348 samples (36.1%), including 108 respiratory syncytial virus (RSV), 64 influenza virus A type H3N2, 47 influenza virus B, 64 coronavirus, 35 rhinovirus, 22 adenovirus, 5 enterovirus, and 3 parainfluenza-fluenza strains. There were 16 mixed infections. RSV infections peaked in the early winter, and influenza viruses A and B infections peaked during the late winter and early spring. There were two peaks of coronavirus infections (late fall and late winter). Other viruses were detected at lower levels throughout the study period. Patients from whom adenovirus was isolated were significantly more likely to have a fever of > 39.5 degrees C than were patients with other detectable viruses (P < 0.001). Furthermore, there was a significant correlation between influenza and cough (P < 0.01) and RSV and bronchiolitis (P < .001). Thus, the current study defined the overall and relative frequencies of respiratory virus detection from nasal swab specimens in patients with an acute flu-like illness in the Rhone-Alpes region of France during a 7-month period. Correlation with clinical signs and symptoms and provisional conclusions regarding seasonality were also determined.


title: [Relationship between epidemiological evidence and fatality rate in patients with severe acute respiratory syndrome].

text: OBJECTIVE To investgate the relationship between epidemiological diagnosis and fatality rate in patients with severe acute respiratory syndrome (SARS). METHODS Epidemiological evidences and the outcomes of 304 patients with confirmed SARS were retrospectively analyzed. Patients included highly contagious cases, cluster cases, and sporadic cases. RESULTS The case fatality rate was 8.2%. The fatality rate had a tendency of increase in an order of sporadic cases, cluster cases, and highly contagious cases (3.9%, 11.4%, and 17.2%, respectively, chi2trend=7.561, P < 0.01). Chi square-test also proved that the fatality rate was higher in older people (chi2trend=27.024, P < 0.01) and in male (male vs female: 12.2% vs 5.5%). A logistic regression model showed that the epidemiological evidence, age, and gender were correlated to fatality rate. By observing changes of the odds ratio for epidemic evidence, age, and gender using forward method, we found epidemic evidence was an independent risk factor related to fatality rate in SARS patients. CONCLUSION The epidemiological evidence is an independent factor related to fatality rate in SARS patients. Highly contagious case has a worse prognosis and higher fatality rate than sporadic cases and cluster cases.


title: Comparative properties of feline coronaviruses in vitro.

text: Two feline coronaviruses were characterized to determine their biological properties in vitro and their antigenic relatedness to a previously recognized feline infectious peritonitis virus and canine coronavirus. The viruses, designated WSU 79-1146 and WSU 79-1683, were shown to have comparable growth curves with the prototype feline infectious peritonitis virus. Treatment of the feline infectious peritonitis virus strains with 0.25% trypsin indicated that they were relatively resistant to proteolytic inactivation when compared with the feline enteric coronavirus strain. This observation may serve as a useful in vitro marker to distinguish closely related members of the feline coronavirus group. Plaque assay results indicated that the feline infectious peritonitis virus strains produced large homogeneous plaques in comparison to the feline enteric coronavirus strain and canine coronavirus, which showed a heterogenous plaque size distribution. No naturally temperature sensitive mutants were detected in either of the feline coronavirus populations. Both of the viruses were antigenically related to feline infectious peritonitis virus and to a lesser extent to canine coronavirus by virus neutralization.


title: Ventilator-associated pneumonia risk decreased by use of oral moisture gel in oral health care.

text: Although oral health care has a preventive effect against ventilator-associated pneumonia (VAP), the most effective method of oral health care in this respect remains to be established. The objective of this single-center, randomized, controlled trial was to investigate the relationship between VAP and various methods of oral health care. All patients included in the study (n=142) were on mechanical ventilation with oral intubation at the intensive care unit of the Tokyo Dental College Ichikawa General Hospital. They were divided into two groups, one receiving standard oral health care (Standard group), and the other receiving oral health care using an oral moisture gel instead of water (Gel group). After removal of the intubation tube, biofilm on cuff of the tube was stained with a disclosing agent to determine the contamination level. Factors investigated included sex, age, number of remaining teeth, intubation time, fever ≥38.5°C, VAP, cuff contamination level, and time required for one oral health care session. No VAP occurred in either group during the study period. The level of cuff contamination was significantly lower in the Gel group than the Standard group, and the time required for one session of oral health care was shorter (p<0.001). Multivariate analysis revealed use of the oral moisture gel as a factor affecting cuff contamination level. Use of an oral moisture gel decreased invasion of the pharynx by bacteria and contaminants together with biofilm formation on the intubation tube cuff. These results suggest that oral health care using an oral moisture gel is effective in preventing cuff contamination.


title: Umbilical KeyPort bilateral laparoscopic orchiectomy in patient with complete androgen insensitivity syndrome.

text: MAIN FINDINGS A 22-year-old woman with complete androgen insensitivity syndrome (CAIS) presenting with primary amenorrhea and normal female external genitalia was referred for laparoscopic gonadectomy. She had been diagnosed several years earlier but was reluctant to undergo surgery. Case HYPOTHESIS Diagnosis of this X-linked recessive inherited syndrome characterizes by disturbance of virilization in males with an AR mutation, XY karyotipe, female genitalia and severely undescended testis with risk of malignization. The optimal time to orchidectomy is not settled; neither the real risk of malignancy in these patients. Early surgery impacts development of a complete female phenotype, with enlargement of the breasts. Based on modern diagnostic imaging using DCE-MRI and surgical technology with single port laparoscopic access we hypothesize that the optimum time for gonadectomy is not at the time of diagnosis, but once feminization has completed. PROMISING FUTURE IMPLICATIONS An umbilical laparoendoscopic single-site access for bilateral gonadectomy appears to be the first choice approach as leaves no visible incision and diminishes the psychological impact of surgery in a patient with CAIS absolutely reassured as female. KeyPort, a single port access with duo-rotate instruments developed by Richard Wolf facilitates this surgery and allows excellent cosmetic results.


title: [Evaluation of the efficacy and safety of corticosteroid in the treatment of severe SARS in Guangdong province with multi-factor regression analysis].

text: OBJECTIVE To investigate the clinical database of severe acute respiratory syndrome (SARS) in Guangdong province and evaluate the efficacy and safety of corticosteroid in the treatment of severe SARS from December 2002 to December 2003. METHODS The detail data of 1 278 SARS patients and borderline cases were collected. Four hundred and two confirmed SARS cases were recruited in our study. Out of them, 358 cases were assigned to the severe SARS group based on the criteria issued by Ministry of Health. Subjects who received steroid (which was converted into methylprednisolone) treatment were further divided into three groups: small dose group (<80 mg/day); moderate dose group (80-320 mg/day); high dose group (>or=320 mg/day). A Logistic regression model was applied to investigate the outcome variables:death, complications, subsequent lung infection and other infections and COX regression was made. RESULTS (1) Small dose of steroid seemed to have protective effect, but it did not reach significant level. (2) COX regression revealed that steroid was not related to instant mortality rate. (3) Length of stay in hospital of patients steroid usage in medium dosage seemed to be 0.619 time less risky than in patients without steroid usage (chi (2)=7.262, P=0.007), and that in patients with immunomodulator (including gamma globulin, thymic peptide and interferon) was 0.671 time less risky than in patients without immunomodulator (chi (2)=10.252, P=0.001). (4)Incidence of infections in patients with steroid was 3.095 times higher than in patients without steroid (chi (2)=4.289, P=0.038). CONCLUSION There is no significant difference in mortality, instant death incidence between steroid treatment and non-steroid treatment group of SARS patients diagnosed with the diagnostic criteria issued by Ministry of Health. However, steroid seem to shorten the length of hospital stay. But attention should be paid that infection rate could be increased in such cases.


title: Chinese herbal medicine for severe acute respiratory syndrome: a systematic review and meta-analysis.

text: OBJECTIVES To review randomized controlled trials (RCTs) evaluating the effects of Chinese herbal medicine for treating severe acute respiratory syndrome (SARS) systematically. DESIGN Electronic and manual searches identified RCTs comparing Chinese medicine integrated to conventional medicine versus conventional medicine alone. Methodological quality of trials was assessed by generation of allocation sequence, allocation concealment, blinding, and intention-to-treat. RESULTS Eight RCTs (488 patients with SARS) were included. The methodological quality was generally low. The combined therapy showed significant reduction of mortality (relative risk 0.32 [95% confidence interval {CI} 0.12 to 0.91]), shortened duration of fever, symptom relief, reductions in chest radiograph abnormalities, and reductions in secondary fungal infections among patients receiving glucocorticoids. There were no significant effects on quality of life or glucocorticoid dosage. CONCLUSION Chinese herbal medicine combined with conventional medicine may have beneficial effects in patients with SARS. The evidence is insufficient because of the low methodological quality of the included trials.


title: Pneumoconiosis prevalence among working coal miners examined in federal chest radiograph surveillance programs--United States, 1996-2002.

text: Coal workers' pneumoconiosis (CWP) is a chronic lung disease caused by inhalation of coal mine dust. To characterize the prevalence of CWP, the National Institute for Occupational Safety and Health (NIOSH) analyzed recent radiographic information from the U.S. National Coal Workers' X-ray Surveillance Program (CWXSP). Established under the Federal Coal Mine Health and Safety Act of 1969, CWXSP is administered by NIOSH under federal regulations. NIOSH is responsible for approving coal miner examination plans, submitted approximately every 5 years by companies that operate underground coal mines. This report summarizes the results of the analysis, which indicate that the overall prevalence of CWP among participating miners continues to decline; however, new cases are occurring among miners who have worked exclusively under current dust exposure limits. An evaluation of the mining conditions that have resulted in these cases is underway.


title: A wireless PDA-based physiological monitoring system for patient transport.

text: This paper proposes a mobile patient monitoring system, which integrates current personal digital assistant (PDA) technology and wireless local area network (WLAN) technology. At the patient's location, a wireless PDA-based monitor is used to acquire continuously the patient's vital signs, including heart rate, three-lead electrocardiography, and SpO2. Through the WLAN, the patient's biosignals can be transmitted in real-time to a remote central management unit, and authorized medical staffs can access the data and the case history of the patient, either by the central management unit or the wireless devices. A prototype of this system has been developed and implemented. The system has been evaluated by technical verification, clinical test, and user survey. The evaluation of performance yields a high degree of satisfaction (mean = 4.64, standard deviation--SD = 0.53 in a five-point Likert scale) of users who used the PDA-based system for intrahospital transport. The results also show that the wireless PDA model is superior to the currently used monitors both in mobility and in usability, and is, therefore, better suited to patient transport.


title: Prevalence of human metapneumovirus and influenza virus infections among Japanese children during two successive winters.

text: BACKGROUND Human metapneumoviruses (hMPVs) are recognized as a leading cause of respiratory infections in young infants in many countries. The objective of this study was to identify links between hMPV and influenza virus infections among children with influenza-like illness. METHOD This study was conducted in 2 influenza seasons (2002-2003 and 2003-2004) at 2 pediatric outpatient clinics in Niigata city, Japan. Nasopharyngeal swabs or aspirates were collected from influenza-like illness patients, and hMPV and influenza were detected by reverse transcription-polymerase chain reaction (RT-PCR). A nucleotide sequence of 352 nucleotides segment of the F gene was performed. RESULTS A total of 765 influenza viruses and 84 hMPV were identified from 1498 nasopharyngeal swabs or aspirates by virus isolation and RT-PCR, respectively. hMPV-positive rates in patients with influenza-like illness were 5.7 and 5.2% in the 2002-2003 and 2003-2004 seasons, respectively. Epidemic curves of influenza and hMPV patients showed similar patterns with peaks in February in 2 influenza seasons. hMPV infections occurred frequently in infants and school children. Approximately 46% of hMPV patients were coinfected with influenza A viruses, but those coinfected cases were not clinically distinct from the others. No coinfection with influenza B viruses was found. Phylogenetic analysis of the hMPV fusion gene sequences revealed that 2 distinct hMPV cocirculated and that completely identical strains in subgroup A were observed over 2 years. CONCLUSIONS HMPV plays an important pathogenic role in patients with influenza-like illness in winter seasons, often in coinfections with influenza A viruses.


title: Infarct in a New Territory After Treatment Administration in the ESCAPE Randomized Controlled Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

text: BACKGROUND AND PURPOSE Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). METHODS The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I-III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days. RESULTS From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow-up noncontrast computed tomography, 11.7% on follow-up magnetic resonance imaging) were identified (5.0% in endovascular treatment arm versus 4.0% in control arm [P=0.7]). The use of intravenous alteplase was associated with a 68% reduction in the odds of INT occurrence (3.0% with versus 9.1% without; odds ratio, 0.32; 95% confidence interval, 0.11-0.96; adjusted for age, sex, and treatment type). No other variables were associated with INTs. INT occurrence was associated with reduced probability of good clinical outcome (common odds ratio, 0.25; 95% confidence interval, 0.09-0.74; adjusted for age, type of treatment, and follow-up scan). CONCLUSIONS INTs are uncommon, detected more frequently on follow-up magnetic resonance imaging, and affect clinical outcome. In experienced centers, endovascular treatment is likely not causal, whereas intravenous alteplase may be therapeutic. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.


title: New point of care test is highly specific but less sensitive for influenza virus A and B in children and adults.

text: The importance of rapid diagnosis of influenza has increased with the availability of neuraminidase inhibitors, which need to be commenced within 48 hr of symptom onset. Furthermore, the recent development of influenza-like clinical syndromes with novel aetiologies (severe acute respiratory syndrome, SARS) has increased the need for rapid and accurate near-patient diagnosis. A new, modified point of care (POC) diagnostic test (ZstatFlu) was assessed on 469 nasopharyngeal aspirates (NPAs) and 260 nose/throat swabs (TS) taken from children and adults. The test was specific (77-98%) for all specimen types for influenza virus A and B, depending upon incubation conditions. However, it was less sensitive, detecting 65-77% of specimens confirmed as positive on culture, direct immunofluorescence or PCR testing. A positive test is useful, for both directing initiation of therapy in the clinician's office, and making a positive diagnosis of influenza in patients with influenza-like clinical syndromes.


Inclusion of biopsies in clinical trials of oncology drugs.


title: [Severe acute respiratory syndrome (SARS)].

text: On November 2002, 305 cases of atypical pneumonia appeared in southern China. In February 2003, cases were reported in Hong Kong and from there the disease spread to many other countries, mainly, China, Hong Kong, Singapore, Vietnam and Toronto in Canada. The syndrome was defined as Severe Acute Respiratory Syndrome SARS), and a person is suspected of having SARS if he/she became ill after November 1 2002, has a fever exceeding 38 degrees C, has symptoms of a respiratory disease and was in a risk area or in close contact with a SARS patient within ten days prior the appearance of symptoms. The World Health Organization has received reports of 4,836 cases, of which 293 persons have died. Most were family members or medical staff treating the patient, persons who came into close and prolonged contact with the patient. The estimated incubation period is two days to one week. Symptoms of the disease include fever, shortness of breath and cough. Ten percent of patients afflicted with SARS require artificial breathing. The mortality rate is 6-7%. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Infection is transmitted from person to person through direct or close contact with airborne droplets or personal objects of an infected person. Patients must be isolated and treated by contact and airborne isolation. Treatment consists of support care and artificial respiration when required. The use of anti-viral medications has not yet proven effective.


British Columbia.


title: Self-state of nurses in caring for SARS survivors.

text: The aim of this study was to analyze nurses' experiences of role strain when taking care of patients with severe acute respiratory syndrome (SARS). We adopted an interpretive/ constructivist paradigm. Twenty-one nurses who had taken care of SARS patients were interviewed in focus groups. The data were analyzed using thematic analysis. The self-state of nurses during the SARS outbreak evolved into that of professional self as: (1) self-preservation; (2) self-mirroring; and (3) self-transcendence. The relationship between self-state and reflective practice is discussed.


title: Cognitive load and performance of health care professionals in donning and doffing PPE before and after a simulation-based educational intervention and its implications during the COVID-19 pandemic for biosafety.

text: INTRODUCTION The Personal Protective Equipment (PPE) is essential to avoid the COVID-19 spread to health care workers. Its use can be difficult, posing a high risk of contamination, mainly during doffing, then with the risk of becoming infected. METHODS We conducted a prospective before-and-after design that used clinical simulation as a research methodology in a clinical simulation center of Colombia. A simulation-based educational intervention with two cases related to COVID-19 was proposed in the emergency room and the intensive care unit. We conducted A workshop for donning and doffing of personal protective equipment (PPE) and a debriefing after the first case. RESULTS In the pre-test, 100% of participants failed donning and doffing PPE, 98.4% were contaminated, only one-person did not contaminate out of. The mean cognitive load was high (7.43±0.9 points). In the post-test, 100% were successful in donning the PPE and 94.8% in doffing; only 9.8% were contaminated. The mean of the cognitive load was low (4.1±1.4 points), and the performance was high (7.9±1.1). Of the total, 73.8% of participants reported overload in the doffing. The most difficulties were in gown/overall, and N95 mask removal. DISCUSSION The PPE donning and doffing is critical and may be changed significantly by active training. In responding to the current COVID-19 pandemic in 2020, activities of training in donning and doffing PPE would provide a means of training personnel, reducing the cognitive load and maybe the risk of contamination and infection of health care workers.


title: The Future of Health Care in the Kurdistan Region - Iraq: Toward an Effective, High-Quality System with an Emphasis on Primary Care.

text: At the request of the Kurdistan Regional Government (KRG), RAND researchers undertook a yearlong analysis of the health care system in the Kurdistan Region of Iraq, with a focus on primary care. RAND staff reviewed available literature on the Kurdistan Region and information relevant to primary care; interviewed a wide range of policy leaders, health practitioners, patients, and government officials to gather information and understand their priorities; collected and studied all available data related to health resources, services, and conditions; and projected future supply and demand for health services in the Kurdistan Region; and laid out the health financing challenges and questions. In this volume, the authors describe the strengths of the health care system in the Kurdistan Region as well as the challenges it faces. The authors suggest that a primary care-oriented health care system could help the KRG address many of these challenges. The authors discuss how such a system might be implemented and financed, and they make recommendations for better utilizing resources to improve the quality, access, effectiveness, and efficiency of primary care.


Impact of COVID-19 on Pediatric Dental Practice in the United States.


Multiplication of canine coronavirus in CRFK cells.


title: Detection of feline coronavirus RNA in feces, tissues, and body fluids of naturally infected cats by reverse transcriptase PCR.

text: A nested reverse transcriptase PCR (RT-nPCR) was developed for the detection of feline coronavirus (FCoV) RNA in the feces, tissues, and body fluids of infected cats. The RT-nPCR was targeted to the highly conserved 3'-untranslated region of the viral genome and will detect most, if not all, feline coronaviruses in the field. With the RT-nPCR, FCoV RNA was detected in plasma samples from experimentally infected cats as early as 2 days postinoculation. FCoV RNA was also detected in serum, plasma, or ascitic fluid samples from 14 of 18 cats (78%) with naturally occurring feline infectious peritonitis (FIP). The use of RT-PCR for FIP diagnosis is limited because of the occurrence of apparently healthy FCoV carriers. These asymptomatic cats shed the virus in the feces and, in a number of cases, also had detectable virus in the plasma. Because of the nature of FCoV infections, our RT-PCR assay with plasma or serum cannot be used to establish a definite diagnosis of FIP. However, this assay does provide a new means to identify asymptomatic FCoV carriers. As such, RT-nPCR will be of use to screen cats before their introduction into FCoV-free catteries. Moreover, this assay provides an important tool to study the epidemiology of FCoV.


title: A clinical prediction rule for diagnosing severe acute respiratory syndrome in the emergency department.

text: BACKGROUND Accurate, objective models of triage for patients with suspected severe acute respiratory syndrome (SARS) could assess risks and improve decisions about isolation and inpatient treatment. OBJECTIVE To develop and validate a clinical prediction rule for identifying patients with SARS in an emergency department setting. DESIGN Retrospective analysis using a 2-step coefficient-based multivariable logistic regression scoring method with internal validation by bootstrapping. SETTING 2 hospitals in Hong Kong. PARTICIPANTS 1274 consecutive patients from 1 hospital and 1375 consecutive patients from another hospital. MEASUREMENTS Points were assigned on the basis of history, physical examination, and simple investigations obtained at presentation. The outcome measure was a final diagnosis of SARS, as confirmed by World Health Organization laboratory criteria. RESULTS Predictors for SARS on the basis of history (step 1) included previous contact with a patient with SARS and the presence of fever, myalgia, and malaise. Age 65 years and older and younger than 18 years and the presence of sputum, abdominal pain, sore throat, and rhinorrhea were inversely related to having SARS. In step 2, haziness or pneumonic consolidation on chest radiographs and low lymphocyte and platelet counts, in addition to a positive contact history and fever were associated with a higher probability of SARS. A high neutrophil count, the extremes of age, and sputum production were associated with a lower probability of SARS. In the derivation sample, the observed incidence of SARS was 4.4% for those assigned to the low-risk group (in steps 1 or 2); in the high-risk group, incidence of SARS was 21.0% for quartile 1, 39.5% for quartile 2, 61.2% for quartile 3, and 79.7% for quartile 4. This prediction rule achieved an optimism-corrected sensitivity of 0.90, a specificity of 0.62, and an area under the receiver-operating characteristic curve of 0.85. LIMITATIONS The prediction rule may not apply to isolated cases occurring during an interepidemic period. Generalizability of the findings should be confirmed in other SARS-affected countries and should be prospectively validated if SARS returns. CONCLUSIONS Our findings suggest that a simple model that uses clinical data at the time of presentation to an emergency department during an acute outbreak predicted the incidence of SARS and provided good diagnostic utility.


title: Acquired thrombasthenia due to inhibitory effect of glycoprotein IIbIIIa autoantibodies.

text: BACKGROUND A 75 year old patient presenting with mucocutaneous bleeding was diagnosed with acquired thrombasthenia. The diagnosis was based on lack of platelet aggregation with adenosine diphosphate (ADP), arachidonic acid and collagen, and normal aggregation induced by ristocetin. OBJECTIVE To study the mechanism of platelet function inhibition in a patient with acquired thrombasthenia. METHODS Aggregation assays of platelets from the patient and healthy controls were performed. In addition, anti-glycoprotein (GP) IIbIIIa antibodies bindingto normal in the presence or absence of the patient's serum was by flow cytometry. RESULTS Aggregation of normal platelets in the presence of patient's plasma was inhibited four- and 2.5-fold in the presence of ADP and arachidonic acid respectively, while collagen-induced aggregation was completely abolished. Ristocetin-induced aggregation was normal. The patient's serum inhibited binding of commercial anti-glycoprotein IIbIIIa antibodies to normal platelets twofold by flow cytometry. Treatment with anti-CD20 monoclonal antibody (rituximab) normalized the patient's platelet aggregation. CONCLUSIONS These results suggest that the patient developed inhibitory anti-GPIIbIIIa autoantibodies that caused acquired thrombasthenia.


title: Profiling serine protease substrate specificity with solution phase fluorogenic peptide microarrays.

text: A novel microarray-based proteolytic profiling assay enabled the rapid determination of protease substrate specificities with minimal sample and enzyme usage. A 722-member library of fluorogenic protease substrates of the general format Ac-Ala-X-X-(Arg/Lys)-coumarin was synthesized and microarrayed, along with fluorescent calibration standards, in glycerol nanodroplets on microscope slides. The arrays were then activated by deposition of an aerosolized enzyme solution, followed by incubation and fluorometric scanning. The specificities of human blood serine proteases (human thrombin, factor Xa, plasmin, and urokinase plasminogen activator) were examined. The arrays provided complete maps of protease specificity for all of the substrates tested and allowed for detection of cooperative interactions between substrate subsites. The arrays were further utilized to explore the conservation of thrombin specificity across species by comparing the proteolytic fingerprints of human, bovine, and salmon thrombin. These enzymes share nearly identical specificity profiles despite approximately 390 million years of divergent evolution. Fluorogenic substrate microarrays provide a rapid way to determine protease substrate specificity information that can be used for the design of selective inhibitors and substrates, the study of evolutionary divergence, and potentially, for diagnostic applications.


title: [Management and prevention of dental emergency during corona virus disease 2019 (COVID-19) epidemic].

text: The outbreak of corona virus disease 2019 (COVID-19) has developed rapidly and the situation of prevention and control is severe. During the epidemic period of COVID-19, due to the particularity of diagnosis and treatment of oral diseases, there is great challenges for how to deal with various types of dental emergency. In order to prevent and control the epidemic situation strictly, and to perform a scientific and orderly clinical diagnosis and treatment of dental emergency, this article provided suggestions on personnel management training, procedures and treatment, protection and disinfection of dental emergency during COVID-19 epidemic, and reference for dental institutions and medical staff.


title: Co-receptor antagonists as HIV-1 entry inhibitors.

text: PURPOSE OF REVIEW A new mechanistic understanding of how HIV-1 enters cells has emerged recently, and these discoveries are now being translated into novel therapeutic agents. Along with CD4, HIV-1 requires a chemokine receptor, CCR5 or CXCR4, as an entry co-receptor, and differential co-receptor selectivity is an important determinant of viral diversity and pathogenesis. CCR5 and CXCR4 blockers have been the focus of much research and are now entering clinical trials. RECENT FINDINGS Several CCR5 antagonists with anti-HIV-1 activity have been developed, including small-molecule agents, monoclonal antibodies and modified chemokines. At least four small-molecule and one antibody CCR5 inhibitor are in various stages of preclinical and clinical testing. Most or all infected individuals harbor CCR5-using variants, and promising findings have been reported from very preliminary clinical studies. CXCR4 antagonists under development include small-molecule and short-peptide inhibitors. Only a subset of late-stage individuals harbor CXCR4-using strains, and early clinical studies of CXCR4 inhibition showed some evidence of suppression in certain individuals. SUMMARY Chemokine receptor antagonists offer great promise as a much-needed new class of antiviral agent. They also raise questions that are unique to agents targeting these cellular receptors, including whether drug resistance will lead to variants with altered co-receptor selectivity, the tolerability of chronically blocking receptors involved in inflammation (CCR5, CXCR4) or essential in development and hematopoesis (CXCR4), and the role of co-receptor phenotyping in selecting blocking agents. In addition to HIV-1 infection, these drugs may also have utility in inflammation, cancer, stem cell transplant and other areas.


title: Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013.

text: We describe a novel spike pseudoparticle neutralisation assay (ppNT) for seroepidemiological studies on Middle East respiratory syndrome coronavirus (MERSCoV) and apply this assay together with conventional microneutralisation (MN) tests to investigate 1,343 human and 625 animal sera. The sera were collected in Egypt as a region adjacent to areas where MERS has been described, and in Hong Kong, China as a control region. Sera from dromedary camels had a high prevalence of antibody reactive to MERS-CoV by MERS NT (93.6%) and MERS ppNT (98.2%) assay. The antibody titres ranged up to 1,280 and higher in MN assays and 10,240 and higher in ppNT assays. No other investigated species had any antibody reactivity to MERS-CoV. While seropositivity does not exclude the possibility of infection with a closely related virus, our data highlight the need to attempt detection of MERSCoV or related coronaviruses in dromedary camels. The data show excellent correlation between the conventional MN assay and the novel ppNT assay. The newly developed ppNT assay does not require Biosafety Level 3 containment and is thus a relatively high-throughput assay, well suited for large-scale seroepidemiology studies which are needed to better understand the ecology and epidemiology of MERS-CoV.


Equine laparoscopy: hemostasis.


title: [Isolation and characteristics of virus culture of porcine epidemic diarrhea virus LJB/03].

text: Porcine epidemic diarrhea virus (PEDV) LJB/03 strain was isolated from the feces of piglets suspected to be suffering from a severe diarrhea in Heilongjiang Province, and was identified by immunofluorescence test, immunelectronmicroscopy, RT-PCR and indirect ELISA assay. Characteristics of the virus culture and the methods of improvement of virus titer were explored. The results showed that the virus had the typical appearance of the coronavirus. Analysis of the nucleotide sequences of RT-PCR products revealed 98% homology with the reference strains. Indirect immunofluorescence assay showed a significant presence of green fluorescence, and an average P/N ratio of 7.6 by indirect ELISA assay. Taken together, these tests showed positive isolation of PEDV. Using the virus plaque purification cloning methods established in the test, the purified PEDV large plaque and small plaque were obtained, and the large plaque and small plaque titers were measured with significant difference. These results provide potential for the application of PEDV on the basis of the biological features of isolated virus.


title: Recognition of cellular receptors by bovine coronavirus.

text: Bovine coronavirus (BCV) initiates infection by attachment to cell surface receptors the crucial component of which is N-acetyl-9-O-acetylneuraminic acid. Inactivation of receptors by neuraminidase treatment and restoration of receptors by enzymatic resialylation of asialo-cells is described as a method to determine (i) the type of sialic acid that is recognized; (ii) the linkage specificity of the viral binding activity; (iii) the minimal amount of sialic acid required for virus attachment. Evidence is presented that both glycoproteins and glycolipids can serve as receptors for BCV provided they contain 9-O-acetylated sialic acid. A model is introduced proposing that after initial binding to sialic acid-containing receptors, the S-protein of BCV interacts with a specific protein receptor. This interaction may result in a conformational change that exposes a fusogenic domain and thus induces the fusion between the viral and the cellular membrane.


title: Navigating the Zika panic.

text: The epidemics of Ebola virus in West Africa and Zika virus in America highlight how viruses can explosively emerge into new territories. These epidemics also exposed how unprepared we are to handle infectious disease emergencies. This is also true when we consider hypothesized new clinical features of infection, such as the associations between Zika virus infection and severe neurological disease, including microcephaly and Guillain-Barré syndrome. On the surface, these pathologies appear to be new features of Zika virus infection, however, causal relationships have not yet been established. Decades of limited Zika virus research are making us scramble to determine the true drivers behind the epidemic, often at the expense of over-speculation without credible evidence. Here we review the literature and find no conclusive evidence at this time for significant biological differences between the American Zika virus strains and those circulating elsewhere. Rather, the epidemic scale in the Americas may be facilitated by an abnormally warm climate, dense human and mosquito populations, and previous exposure to other viruses. Severe disease associated with Zika virus may therefore not be a new trait for the virus, rather it may have been overlooked due to previously small outbreaks. Much of the recent panic regarding Zika virus has been about the Olympics in Brazil. We do not find any substantial evidence that the Olympics will result in a significant number of new Zika virus infections (~10 predicted) or that the Olympics will promote further epidemic spread over what is already expected. The Zika virus epidemic in the Americas is a serious situation and decisions based on solid scientific evidence - not hyped media speculations - are required for effective outbreak response.


title: Candidate autoantigens in multiple sclerosis.

text: Multiple sclerosis is an inflammatory demyelinating CNS disease of putatively autoimmune origin. Novel models of experimental autoimmune encephalomyelitis (EAE) have demonstrated that T cells specific for various myelin and even nonmyelin proteins are potentially encephalitogenic. The encephalitogenic T cell response directed against different CNS antigens not only determines the lesional topography of CNS inflammation but also the composition of the inflammatory infiltrates. The heterogeneity of the lesional distribution seen in EAE might therefore be useful for the understanding of the various clinical subtypes seen in MS. In this review the possible candidate autoantigens in MS are discussed with special regard to the human T cell and B cell responses against various myelin and nonmyelin proteins.


title: Achieving clinical equality in an influenza pandemic: patent realities.

text: A twenty-first century novel influenza A (H1N1) pandemic is currently unfolding, and the eventual scope of this public health crisis is not clear. In addition, ongoing surveillance of the avian influenza A (H5N1) virus reveals outbreaks of human-to-human transmission of the virus, with significant mortality. Effective pandemic management depends on pharmaceutical intervention with two different clinical objectives: the generation of an immune response to specific viral strains (vaccination) and the reduction of viral replication in an infected individual (antiviral administration). The ability to offer pharmaceutical interventions for a public health crisis depends on three factors: development, capacity, and access. Pharmaceutical measures must be developed, capacity must be established, and access must be ensured. The article discusses the three nodes of patenting that influence the availability of pharmaceutical countermeasures in an influenza pandemic. Identification of the causative influenza virus is the first step in pandemic management and precedes vaccine design, and the virus and its RNA sequence are both knowledge assets and inputs for vaccine design. Vaccine development, therefore, will be influenced by any patents on the genetic sequences or proteins of the pandemic virus, as well as on novel methods for vaccine production, the actual vaccine or adjuvant technology, all of which are relevant to the assembly of a working vaccine on short notice. Pharmaceutical treatment of influenza infection during a pandemic could also rely on use of patented antiviral drugs, whose efficacy may be revealed as the pandemic unfolds. Unlike vaccines, these are not generally developed de novo for a pandemic, but their availability could be dependent on the exercise of patent rights by market incumbents. Patent rights could control capacity, which may determine access. Pandemic planning must consider how patenting can influence development, capacity and access to pharmaceutical interventions. The national and international public health authorities are slowly integrating intellectual property considerations into pandemic planning. Further integration will anticipate the emergence of patent claims, identify any relevant patents, encourage access norms, and consider the use of legal mechanisms that could alleviate patent-mediated obstacles to the availability of critical products and methods that may be patented. Pandemic management must also co-exist with existing efforts to control seasonal influenza outbreaks. The article analyzes the intersection of patent nodes relevant to vaccine development and to antiviral distribution during a global influenza pandemic, identifying where such patents may facilitate or inhibit the availability of pharmaceutical countermeasures, and offers preliminary observations on the emerging novel H1N1 pandemic. The goal of international clinical equality is essential for the eradication of an influenza pandemic, and strategies for its achievement can also be applied to other diseases.


title: Postoperative Cerebrospinal Fluid Leak Rates with Subfascial Epidural Drain Placement after Intentional Durotomy in Spine Surgery.

text: Study Design Retrospective chart review. Objective Postoperative cerebrospinal fluid (CSF) leak is a known complication of intraoperative durotomy. Intraoperative placement of subfascial epidural drains following primary dural repair has been proposed as a potential management strategy to prevent formation of CSF cutaneous fistula and symptomatic pseudomeningocele. Here we describe our experience with subfascial drain after intentional durotomy. Methods Medical records of patients who underwent placement of subfascial epidural drains during spinal procedures with intentional intraoperative durotomies over a 4-year period at two institutions were retrospectively reviewed. Primary outcomes of interest were postoperative CSF cutaneous fistula or symptomatic pseudomeningocele formation. Results Twenty-five patients were included. Mean length of follow-up was 9.5 months. Twelve patients (48%) underwent simultaneous arthrodesis. The average duration of the drain was 5.3 days with average daily output of 126.5 mL. Subgroup analyses revealed that average drain duration for the arthrodesis group was 6.33 days, which is significantly greater than that of the nonfused group, which was 3.7 days (p = 0.016). Similarly, the average daily drain output for the arthrodesis subgroup at 153.1 mL was significantly higher than that of the nonfused subgroup (86.8 mL, p = 0.04). No patient developed postoperative CSF cutaneous fistula or symptomatic pseudomeningocele or had negative sequelae associated with overdrainage of CSF. One patient had a delayed wound infection. Conclusions The intraoperative placement of subfascial epidural drains was not associated with postoperative development of CSF cutaneous fistula, symptomatic pseudomeningocele, overdrainage, or subdural hematoma in the cases reviewed. Subfascial closed wound drain placement is a safe and efficacious management method after intentional spinal durotomies. It is particularly helpful in those who undergo simultaneous arthrodesis, as those patients have statistically higher daily drain output and longer drain durations.


title: Traumatic Rupture of a Duodenal Diverticulum: Case Report and Review of the Literature.

text: Duodenal diverticula are relatively common and usually asymptomatic (95%). Their perforation is a rare but harmful event. Traumatic perforation is exceptional. We report the case of a patient with such a lesion following a blunt trauma secondary to a car accident, and review the literature. Clinical presentation is aspecific and diagnosis is based upon CT scan imaging. Surgery is the recommended treatment consisting of diverticulectomy with transverse duodenal closure of the duodenum associated with retroperitoneal drainage.


title: Isolation of avian paramyxovirus 1 from a patient with a lethal case of pneumonia.

text: An unknown virus was isolated from a lung biopsy sample and multiple other samples from a patient who developed a lethal case of pneumonia following a peripheral blood stem cell transplant. A random PCR-based molecular screening method was used to identify the infectious agent as avian paramyxovirus 1 (APMV-1; a group encompassing Newcastle disease virus), which is a highly contagious poultry pathogen that has only rarely been found in human infections. Immunohistochemical analysis confirmed the presence of APMV-1 antigen in sloughed alveolar cells in lung tissue from autopsy. Sequence from the human isolate showed that it was most closely related to virulent pigeon strains of APMV-1. This is the most completely documented case of a systemic human infection caused by APMV-1 and is the first report of an association between this virus and a fatal disease in a human.


title: Characterization of transcription factor binding to human papillomavirus type 16 DNA during cellular differentiation.

text: Human papillomaviruses (HPVs) require terminal differentiation of the host cell to produce infectious virions. The process of viral maturation involves a variety of changes in the expression/activity of host proteins that lead to high-level replication of the viral genome and expression of the late viral genes. Although the late promoter regions of HPV type 16 (HPV-16) are still not fully characterized, differentiation-dependent regulation of viral genes is thought to involve changes in the binding of host cell transcription factors to the viral promoter and regulatory regions. Currently, very little is known about specific cellular transcription factors involved in this process. We used the Panomics TransSignal protein/DNA array to identify changes in the levels of cellular transcription factors during methylcellulose-induced differentiation of W12 (20863) cells containing HPV-16. We then identified the differentially expressed transcription factors that specifically bind to HPV-16 DNA, including the known promoter and regulatory regions. We have validated the results obtained from the Panomics array by Western blot analysis. Furthermore, by chromatin immunoprecipitation assays, we have shown that many of the transcription factors identified in the above screen bind to the HPV-16 promoter/regulatory sequences in vivo and that the level of this binding is increased during differentiation. This approach identified approximately 30 transcription factors that specifically bind to HPV-16 sequences and may be involved in regulating HPV-16 transcription during differentiation. Although some of these transcription factors have previously been suggested to be involved in HPV-16 transcription, a number of them represent novel viral DNA-host protein interactions.


title: Multiple sclerosis, an autoimmune inflammatory disease: prospects for its integrative management.

text: Multiple sclerosis (MS) is aptly named for the many scars it produces in the brain and spinal cord. A sometimes fatal, often debilitating disease, MS features autoimmune inflammatory attack against the myelin insulation of neurons. Thymus derived (T) cells sensitized against myelin self-antigens secrete tumor necrosis factor, cytokines, prostaglandins, and other inflammatory mediators that strip away the myelin and sometimes destroy the axons. Familial and twin inheritance studies indicate MS is mildly heritable. No single MS locus has been identified, but an HLA haplotype has been implicated. Unique geographic distribution of the disease is best attributed to some combination of vitamin D abnormality and dietary patterns. No pharmaceutical or other therapies exist that confer prolonged remission on MS, and obvious interrelationships between toxic, infectious, and dietary factors make a persuasive case for integrative management. The time-proven MS diet meticulously keeps saturated fats low, includes three fish meals per week, and eliminates allergenic foods. Dietary supplementation for MS minimally requires potent vitamin supplementation, along with the thiol antioxidants, the anti-inflammatory omega-3 fatty acids, and adaptogenic phytonutrients. Gut malabsorption and dysbiosis can be corrected using digestive enzymes and probiotics. Long-term hyperbaric oxygen therapy can slow or remit the disease. Transdermal histamine offers promise, and adenosine monophosphate may sometimes benefit. Chronic viruses and other infectious load must be aggressively treated and exercise should maintain muscle tone and balance. Early intervention with integrative modalities has the potential to make MS a truly manageable disease.


Community acquired pneumonia (CAP) in children in the new vaccination era.


title: Viral proteomics: global evaluation of viruses and their interaction with the host.

text: Viruses constantly adapt to and modulate the host environment during replication and propagation. Both DNA and RNA viruses encode multifunctional proteins that interact with and modify host cell proteins. While viral genomes were the first complete sequences known, the corresponding proteomes are only now elucidated, with some surprising results. Even more daunting is the task to globally monitor the impact of viral infection on the proteome of the host cell and many technical hurdles must still be overcome in order to facilitate robust and reproducible measurements. Further complicating the picture is the dynamic nature of proteins, including post-translational modifications, enzymatic cleavage and activation or destruction by proteolytic events. Nevertheless, several promising studies have been published using high-throughput methods directly measuring protein abundance. Particularly, quantitative or semiquantitative mass spectrometry-based analysis of viral and cellular proteomes are now being used to characterize viruses and their host interaction. In addition, the full set of interactions between viral and host proteins, the interactome, is beginning to emerge, with often unexpected interactions that need to be carefully validated. In this review, we will discuss two major areas of viral proteomics: first, virion proteomics (such as the protein characterization of viral particles) and second, proteoviromics, including the viral protein interactomics and the quantitative analysis of host cell proteome during viral infection.


Sudden acute respiratory syndrome.


title: Phylogenetic studies of bovine coronaviruses isolated in Japan.

text: Molecular analysis of the polymorphic region of the bovine coronavirus (BCoV)-S gene using recent Japanese field isolates and reference strains revealed that the 148 isolates collected from 1999 to 2008 from 13 prefectures, covering all regions of Japan (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku, Shikoku, and Kyusyu region) and divided into 3 clusters, show distinctive divergence from the prototype enteric BCoV strains. Almost all isolates after 2005 were clustered into group 4, and there was no regional specificity in these clusters. To differentiate the genotypes without sequencing, a simple technique-reverse transcriptase-polymerase chain reaction/restriction fragment length polymorphism analysis (RT-PCR/RFLP)-was developed. The availability of a simple and easy diagnostic assay will enable larger epidemiological studies of BCoV.


Anthropology. Coral ages show Hawaiian temples sprang from political revolution.


title: High-throughput sequencing in veterinary infection biology and diagnostics.

text: Sequencing methods have improved rapidly since the first versions of the Sanger techniques, facilitating the development of very powerful tools for detecting and identifying various pathogens, such as viruses, bacteria and other microbes. The ongoing development of high-throughput sequencing (HTS; also known as next-generation sequencing) technologies has resulted in a dramatic reduction in DNA sequencing costs, making the technology more accessible to the average laboratory. In this White Paper of the World Organisation for Animal Health (OIE) Collaborating Centre for the Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine (Uppsala, Sweden), several approaches and examples of HTS are summarised, and their diagnostic applicability is briefly discussed. Selected future aspects of HTS are outlined, including the need for bioinformatic resources, with a focus on improving the diagnosis and control of infectious diseases in veterinary medicine.


title: Surgical care in Jamaica in the laparoendoscopic era: challenges and future prospects for developing nations.

text: In an era of technology-dependent surgery, Jamaica and other developing countries must deal with the wide disparity between their surgical practices and those of developed nations. Although there is still a place for the well-trained surgeon, the current emphasis in developed nations is less on the individual surgeon and more on the surgery team and system, with increasing costs despite diminishing government support. At the University of the West Indies, we are challenged to continue providing appropriate service and training for the Caribbean region, but we hope that a combination of fellowship-trained team leaders and partnerships with resource-rich institutions will enable us to meet this challenge and to meet the health care needs of our populace.


title: An evidence base for International Health Regulations: quantitative measurement of the impacts of epidemic disease on international trade.

text: When cholera broke out in Mozambique, Kenya, Tanzania and Uganda in 1997, an urgent measure was filed with the Sanitary and Phytosanitary Committee of the World Trade Organization, by the European Union, citing the protection of human health, to limit imports of fish products. The authors analysed import data on specified products over time to quantify the trade impact of this measure. Using previous specific trade trends, the authors modelled expected trade flows and compared observed imports with expected imports to calculate the potential cost of lost trade. The conclusion of this analysis was that the impact of European restrictions on fish exports from Mozambique, Kenya, Tanzania and Uganda on the economies of these African countries was at least US dollar 332,217,415 for the years 1998 to 2002. Insights from such quantitative studies will be important in making policy choices under the revised International Health Regulations of the World Health Organization and should inform the discussion about the adoption of these regulations.


title: Efficacy and patency of primary stenting for hepatic venous outflow obstruction after living donor liver transplantation.

text: BACKGROUND Hepatic venous outflow is important for graft survival in living donor liver transplantation (LDLT). If hepatic venous outflow obstruction occurs, hepatic vein stenting is considered to restore the patency. PURPOSE To retrospectively evaluate the efficacy and patency of primary hepatic vein stenting for hepatic venous outflow obstruction (HVOO) after LDLT. MATERIAL AND METHODS Percutaneous interventions, including hepatic vein stent placement with or without balloon angioplasty, were performed in 21 patients who had undergone LDLT and had HVOO confirmed through hepatic venography or manometry, including the patients who had a structural abnormality. Two stents each were inserted in four patients; therefore, the total number of treated anastomoses was 25. Technical success, patency rates, and pressure gradients between hepatic veins and the right atrium were evaluated in 19 patients each. RESULTS Technical success was achieved in 25 of 26 vessels (96%). The mean interval between operation and stenting was 43 days. After the procedure, the follow-up period was a mean 530 days. The mean pressure gradient decreased from 8.5 mmHg to 2.1 mmHg after treatment (P < 0.01). The patency rates of the 25 vessels were 80% at 1, 2, and 3 years after stent placement. However, middle hepatic vein stenting revealed a low patency rate (all were 36%). Three of seven stents (43%) in the middle hepatic vein occluded during follow-up. CONCLUSION Percutaneous primary hepatic vein stent replacement is an effective treatment for HVOO after LDLT.


Otitis media: a preventable disease? Proceedings of an international symposium organized by the Marcel Mérieux Foundation, Veyrier-du-Lac, France, February 13 to 16, 2000.


title: Basilar Artery Thrombosis in a Child Treated With Intravenous Tissue Plasminogen Activator and Endovascular Mechanical Thrombectomy.

text: Basilar artery occlusion in children is rare. It has a high mortality and morbidity if recanalization is not achieved before extensive brainstem infarction has occurred. An 11-year-old boy presented with a clinical and radiological "top-of-the-basilar" syndrome. Intravenous tissue plasminogen activator was administered, and the patient was immediately referred to the regional stroke center. Subsequent mechanical thrombectomy using a Solitaire stent (Solitaire FR stent; ev3, Irvine, CA, USA) resulted in clot removal and recanalization of the basilar artery 4 hours after stroke onset. The patient made a full clinical recovery. To the authors' knowledge this is the first report on basilar artery occlusion in a child treated with "bridging" therapy, the combination of intravenous thrombolysis and endovascular thrombectomy. If the diagnosis can be made within the time window for intravenous thrombolysis (4.5 hours), the present case suggests that bridging therapy in pediatric basilar artery occlusion can be safe and effective.


WHO global conference on severe acute respiratory syndrome (SARS).


title: Characterization of human cytomegalovirus UL145 and UL136 genes in low-passage clinical isolates from infected Chinese infants.

text: BACKGROUND Human cytomegalovirus (HCMV) is a leading cause of morbidity and mortality in immunocompromised individuals. The unique long b' (ULB') region of HCMV contains at least 19 open reading frames (ORFs); however, little is known about the function of UL145 and UL136. We characterized UL145 and UL136 in low-passage clinical isolates from Chinese infants. MATERIAL/METHODS The clinical strains of HCMV were recovered from the urine from HCMV-infected infants. Human embryonic lung fibroblasts (HELFs) were infected with clinical isolates of HCMV, and the viral DNA and mRNA for UL145 and UL136 were analyzed by polymerase chain reaction (PCR) and sequencing techniques. We also predicted the structure and function of UL145 and UL136 proteins. RESULTS Sixty-two Chinese infants infected with HCMV were recruited into this study and the clinical isolates were recovered from the urine. Two strains among the low-passage isolates, D2 and D3, were obtained. The UL145 and UL136 sequences were deposited with GenBank under accession numbers of DQ180367, DQ180381, DQ180377, and DQ180389. The mRNA expression of both UL145 and UL136 was confirmed by reverse transcription (RT-PCR) assays. UL145 was predicted to contain 1 protein kinase C phosphorylation site, 2 casein kinase II phosphorylation sites and a zinc finger structure. UL136 was predicted to contain a protein kinase C phosphorylation site, N-myristoylation site, cAMP- and cGMP-dependent protein kinase phosphorylation site and tyrosine kinase II phosphorylation site. Both UL145 and UL136 are highly conserved. CONCLUSIONS UL145 may act as an intranuclear regulating factor by direct binding to DNA, while UL136 may be a membrane receptor involving signal transduction.


The health of the public is the foundation of prosperity: the work of the Public Health Agency of Canada at home and around the world.


title: Murine coronavirus-induced hepatitis: JHM genetic background eliminates A59 spike-determined hepatotropism.

text: Recombinant murine coronaviruses, differing only in the spike gene and containing the strain A59 (moderately hepatotropic) and JHM (neurotropic) spike genes in the background of the JHM genome, were compared for the ability to replicate in the liver and induce hepatitis in weanling C57BL/6 mice. Interestingly, expression of the A59 spike glycoprotein within the background of the neurotropic JHM strain does not reproduce the A59 hepatotropic phenotype. Thus, the JHM genetic background plays a dominant role over the spike in the determination of hepatotropism.


title: Mouse studies of SARS coronavirus-specific immune responses to recombinant replication-defective adenovirus expressing SARS coronavirus N protein.

text: 1. A recombinant adenovirus encoding SARS coronavirus(SARS-CoV) nucleocapsid protein (rAd-N) was constructed. 2. The ability of the rAd-N to induce anti-SARS-CoV N antibody production and cellular immune responses was evaluated in an HLA-A2.1/Kb transgenic mouse model.


title: Roles of spike protein in the pathogenesis of SARS coronavirus.

text: 1. Infection with SARS coronavirus (SARS-CoV) induces a cellular stress condition known as the unfolded protein response (UPR). UPR induction is mediated primarily by viral spike (S) protein. The modulation of UPR by S protein involves activation of PERK protein kinase. Other branches of the UPR pathways controlled by IRE1 and ATF6 proteins, respectively, are not involved. 2. The protease inhibitor Ben-HCl effectively suppresses SARS-CoV infection by blocking virus entry. Viral infectivity is associated with the cleavage of S protein by the cellular protease factor Xa. 3. Two new aspects of the interaction between SARS-CoV S protein and the cell have been defined. These have important implications in the pathogenesis of SARS, providing opportunities for developing vaccines and antivirals against SARS-CoV. 4. Counteracting the UPR and targeting the cleavage of S protein with small molecule pharmaceutical agents represent two new anti-SARS-CoV strategies. 5. The receptor-binding domain of S protein delivered via adeno-associated virus can efficiently induce mucosal immunity and provide long-term protection against SARS-CoV infection.


title: MultiCode-PLx system for multiplexed detection of seventeen respiratory viruses.

text: The MultiCode-PLx system (EraGen Biosciences, Inc., Madison, WI) for the detection of respiratory viruses uses an expanded genetic alphabet, multiplex PCR chemistry, and microsphere flow cytometry to rapidly detect and specifically identify 17 different respiratory viruses directly in clinical specimens. The MultiCode-PLx system was tested in parallel with direct fluorescent-antibody (DFA) staining and rapid shell vial culture (R-mix cells; Diagnostic Hybrids, Inc. Athens, OH) with 354 respiratory specimens from adult patients that were submitted to the clinical virology laboratory at the Emory University Hospital. Single-target PCRs were performed with retained samples to confirm the positive results obtained with the MultiCode-PLx system for viruses not covered by DFA and R-mix culture (metapneumovirus, coronaviruses [CoV], parainfluenza viruses 4a and 4b, and rhinoviruses) and to resolve any discrepancies between the DFA and R-mix culture and the MultiCode-PLx results for viruses common to both systems. Respiratory viruses were detected in 77 (21.8%) and 116 (32.7%) specimens by DFA and R-mix culture and with the MultiCode-PLx system, respectively. Among the viruses common to both systems, the MultiCode-PLx system detected significantly more influenza A viruses (P = 0.0026). An additional increased diagnostic yield with the MultiCode-PLx system resulted from the detection of human metapneumovirus (HMPV) in 9 specimens, human CoV (HCoV) in 3 specimens, and human rhinovirus (HRV) in 16 specimens. Also, two mixed viral infections were detected by the MultiCode-PLx system (HCoV OC43 and HRV infections and HMPV and HRV infections), but none were detected by DFA and R-mix culture. Single-target PCRs verified the results obtained with the MultiCode-PLx system for 73 of 81 (90.1%) specimens that had discordant results or that were not covered by DFA and R-mix culture. The MultiCode-PLx system provides clinical laboratories with a practical, rapid, and sensitive means for the massively multiplexed molecular detection of common respiratory viruses.


title: 257 incidental appendectomies during total laparoscopic hysterectomy.

text: OBJECTIVE This retrospective observational report analyzes the demographics, blood loss, length of surgical duration, number of days in the hospital, and complications for 821 consecutive patients undergoing total laparoscopic hysterectomy over a 11-year period stratified by incidental appendectomy. METHODS A retrospective chart abstraction was performed. ANOVA and chi-square tests were performed with significance preset at P<0.05. RESULTS Of 821 consecutive patients undergoing total laparoscopic hysterectomy, 257 underwent elective appendectomy with the ultrasonic scalpel, either as part of their staging, treatment for pelvic pain, or prophylaxis against appendicitis. Comparing the 2 groups, no difference existed in mean age of 50+/-10 years or mean BMI of 27.6+/-6.7. Both groups had a similar mean blood loss of 130 mL. Surgery took less time (137 vs 118 minutes, P<0.0012) and the hospital stay was shorter in the appendectomy group (1.5 vs 1.2, P<0.0001) possibly because it was performed incidentally in most cases. No complications were attributable to the appendectomy, and complication types and rates in both groups were similar. Though all appendicies appeared normal, pathology was documented in 9%, including 3 carcinoid tumors. CONCLUSIONS Incidental appendectomy during total laparoscopic hysterectomy is not associated with significant risk and can be routinely offered to patients planning elective gynecologic laparoscopic procedures, as is standard for open procedures.


title: Comparison of transobturator tape surgery using commercial and hand made slings in women with stress urinary incontinence.

text: PURPOSE To compare the complications and success rates of hand-made sling with commercial sling used in transobturator tape (TOT) surgery. MATERIALS AND METHODS From 2008 to 2010, hand-made slings were used in TOT surgery, whereas commercial slings were used from 2010 to 2013 in our clinic. Overall 102 patients were included in the study. Patients were categorized into 2 groups: group 1 had hand-made (polypropylene monofilament) slings, while group 2 had commercial slings (polypropylene monofilament). We retrospectively reviewed 1-year follow-up results of the whole cohort. Ages, body mass indexes, menopausal status, operation time, cost of sling, success of operation and complications were recorded. All these data were compared between the 2 groups. RESULTS There were 41 patients (54.29 ± 9.88 years) in group 1 and 61 patients (52.82 ± 9.85 years) in group 2. Menopausal status and body mass index (28.1 vs. 29.2 kg/m² respectively) were similar for both groups. Previous history of incontinence or pelvic organ prolapse surgery (P = .046), mean duration of the procedure (P = .001), and vaginal extrusion rate (P = .016) were significantly lower in group 2. The cost of the sling was higher in group 2 than in group 1. There was no significant difference in success of operation between the groups (P = .319). CONCLUSION According to our results, hand-made mesh is a viable option in TOT surgery with similar efficacy, but surgeons should be careful in terms of vaginal extrusion.


What should change in nursing practice over the next five years?


title: Serum C-reactive protein in children with adenovirus infection.

text: OBJECTIVES (1) To evaluate serum C-reactive protein (CRP) concentrations in children with adenovirus infection, and (2) to compare CRP concentrations in adenovirus and influenza virus infection. PATIENTS AND METHODS Retrospective, comparative single-center study conducted in Emergency Department patients of a paediatric tertiary care center. Comparison of CRP in adenovirus infection and influenza was performed in patient groups stratified according to age and duration of fever. RESULTS In 87 children with adenovirus infection (median age, 1.5 years; interquartile range, 0.9-3.0), CRP levels of <2 mg/L, <10 mg/L, and <100 mg/L were found in 4 (4%), 12 (13%), and 66 (76%) patients, respectively. Median CRP in the children with adenovirus infection and in 130 children with influenza was 49 mg/L (21-96) and 9 mg/L (3-20), respectively (p = 0.001). A statistically significant difference remained when these 2 patient groups were stratified according to age (=2 vs. >2 years) and duration of fever (=3 vs. >3 days) (p <0.001). In adenovirus infection CRP concentrations were unrelated to age, duration of fever and severity of illness, as judged by the extent of mucosal involvement and by the frequency and duration of hospitalisation. CONCLUSION Paediatric adenovirus infection is associated with substantially elevated CRP concentrations in the absence of secondary bacterial infection. CRP levels were independent of the duration of illness, indicating that adenoviruses trigger an immediate inflammatory host response resembling invasive bacterial infection.


title: How long should we treat community-acquired pneumonia?

text: PURPOSE OF REVIEW The studies reviewed in this article suggest that a shorter duration of antibiotic therapy is comparable to standard therapy in the treatment of community-acquired pneumonia and promotes reduction of adverse events, microbial resistance, cost, and improved patient compliance. RECENT FINDINGS Community-acquired pneumonia has traditionally been treated with a 7-14-day course of antimicrobial therapy. Since there have been few well controlled trials regarding the optimal duration of therapy, however, there has been no consensus on length of therapy among different organizational guidelines. Several recent studies have demonstrated that shorter course antibiotic regimens are effective in the treatment of community-acquired pneumonia. SUMMARY Short-course antibiotic therapy is equivalent to standard length of therapy for clinical cure and bacterial eradication. Minimization of drug exposure, however, reduces selection pressure for resistant strains, strengthens patient compliance, and potentially reduces adverse events such as Clostridium difficile infections.


title: Imaging of unusual diffuse lung diseases.

text: PURPOSE OF REVIEW Computed tomography scans are commonly used in imaging lung diseases. As more information accumulates, patterns of rare or new diseases on CT scans are being increasingly reported. Several pulmonary diseases have distinguishing features, which are better delineated on high resolution CT scans than plain chest radiographs. The radiographic features of unusual diffuse lung diseases published in the past two years are described. RECENT FINDINGS Severe acute respiratory syndrome generally manifests as focal or diffuse bilateral areas of consolidation on chest radiography and reticulation with ground-glass attenuation commonly seen on CT scans. A normal HRCT rules out the diagnosis of Pneumocystis carinii pneumonia while a normal chest radiograph does not. Immunocompromised patients without AIDS, who have CMV pneumonia, generally demonstrate a combination of ground-glass attenuation, air-space consolidation, and small nodules on HRCT. Nodules less than 10 mm in size in immunocompromised patients are highly suggestive of viral infections. Bronchial wall thickening on HRCT associated with cavitating nodules is suggestive of Wegner granulomatosis in the appropriate clinical setting. Small cysts may be seen in a minority of patients with subacute hypersensitivity pneumonitis and centrilobular emphysema in chronic farmer's lung. Reversed halo sign has a high specificity for cryptogenic organizing pneumonia. The triad of ground-glass opacities, ill-defined centrilobular nodules and cysts and focal areas of air trapping is highly suggestive of subacute hypersensitivity pneumonitis. SUMMARY Familiarizing with radiographic and CT scan patterns may help the clinician to exclude certain diagnoses and narrow the differential diagnosis for others.


title: Circulating lupus anticoagulant and probable systemic lupus erythematosus in a cat.

text: An adult domestic short hair cat was presented in a critical condition with icterus. Various investigations demonstrated the presence of haemolytic anaemia and hepatic abnormalities, as well as significant coagulation defects. Systemic lupus erythematosus (SLE) was suggested as a possible cause.


Purpose: Brain metastases are a common complication of cancer and occur in about 15 - 40 % of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Materials and Methods: Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Results: Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADClymphoma 0.92 [0.83 - 1.07] vs. ADCno_lymphoma 1.35 [1.10 - 1.64] P = 0.001). Further differentiation between types of metastases was not possible using FA and ADC. Conclusion: There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis. Key Points: • Histopathological subtypes of brain metastases/CNS lymphomas show different morphologic features on MRI• Primary CNS lymphomas show significantly reduced ADC values• DTI is not a reliable tool for differentiation between brain metastases Citation Format: • Bette S, Wiestler B, Delbridge C et al. Discrimination of Different Brain Metastases and Primary CNS Lymphomas Using Morphologic Criteria and Diffusion Tensor Imaging. Fortschr Röntgenstr 2016; 188: 1134 - 1143.


title: Over expression of a synthetic gene encoding interferon lambda using relative synonymous codon usage bias in Escherichia coli.

text: Interferon Lambda (IFN-λ) is a type III interferon which belongs to a novel family of cytokines and possesses antiviral and antitumor properties. It is unique in its own class of cytokines; because of the specificity towards its heterodimer receptors and its structural similarities with cytokines of other classes. This renders IFN-λ a better choice for the treatment against many diseases including viral hepatitis and human coronavirus (HCoV-EMC). The present study describes a computational approach known as relative synonymous codon usage (RSCU); used to enhance the expression of IFN-λ protein in a eukaryotic expression system. Manually designed and commercially synthesized IFN-λ gene was cloned into pET-22b expression plasmid under the control of inducible T7-lac promoter. Maximum levels of IFN-λ expression was observed with 0.4 mM IPTG in transformed E. coli incubated for 4 hours in LB medium. Higher concentrations of IPTG had no or negative effect on the expression of IFN-λ. This synthetically over expressed IFN-λ can be tested as a targeted treatment option for viral hepatitis after purification.


title: Pandemic flu: lessons from the Toronto SARS outbreak.

text: A review of the severe acute respiratory syndrome outbreak in Ontario in 2003 found that there had been several faults in healthcare services and that these had contributed to the spread of infection and the deaths of two nurses. This article argues that, six years on, these faults have not been rectified and that Ontario healthcare services may be unprepared for an H1N1 outbreak. The assistant deputy public health minister of Toronto offers her response.


title: Neuropathology of multiple sclerosis-new concepts.

text: Multiple sclerosis is a chronic inflammatory disease of the central nervous system with profound heterogeneity in clinical course, neuroradiological presentation and response to therapy. The pathological analysis of 235 actively demyelinating lesions coming from three centers revealed different structural and immunological features suggesting that different pathogenetic mechanisms are involved in lesion formation. On the basis of the presence or absence of immunoglobulin and complement deposition, myelin protein loss and the patterns of oligodendrocyte degeneration beside a T cell- and macrophage-dominated immune response, four distinct patterns of demyelination have been identified. In this short review, possible paraclinical markers for tissue destruction on the basis of the main features of myelin destruction are discussed. Furthermore, the importance of early axonal damage in multiple sclerosis is highlighted.


title: Identification of antibody against porcine coronavirus in human milk.

text: A total of 239 human milk samples collected from mothers in Chiba City, Japan during 1994-1997 were tested for the presence of anti-coronavirus antibody. Interestingly, twelve human milk samples were positive for IgA against porcine transmissible gastroenteritis coronavirus, and this represented 5%. These findings provided evidence that the interspecies transmission of coronavirus between human and porcine might occur in nature. This report is noteworthy because it is the first, to the best of our knowledge, demonstrating the presence of antibody against porcine transmissible gastroenteritis coronavirus in human milk.


title: Spontaneous pneumomediastinum in patients with severe acute respiratory syndrome.

text: Spontaneous pneumomediastinum (SP) unrelated to assisted ventilation is a newly recognised complication of severe acute respiratory syndrome (SARS). The objective of the present study was to examine the incidence, risk factors and the outcomes of SP in a cohort of SARS victims from a community outbreak. Data were retrieved from a prospectively collected database of virologically confirmed SARS patients. One hundred and twelve cases were analysable, with 13 patients developing SP (11.6%) at a mean +/- SD of 19.6 +/- 4.6 days from symptom onset. Peak lactate dehydrogenase level was associated with the development of SP. SP was associated with increased intubation and a trend towards death. Drainage was required in five cases. For patients who survived, the SP and/or the associated pneumothoraces took a median of 28 days (interquartile range: 15-45 days) to resolve completely. In conclusion, spontaneous pneumomediastinum appeared to be a frequent complication of severe acute respiratory syndrome. Further research is needed to investigate its pathogenesis.


title: [Viral Hepatitis].

text: HBV and HCV infection proceeds to chronic infection, and anti-cancer chemotherapy is contraindicated in patients with decompasated liver cirrhosis caused by both viruses. Reactivation of HBV refers to an increase in the HBV load caused by chemotherapy in a patient with HBV infection. Reactivation of HBV is classified into 2 categories: reactivation in a carrier and reactivation in a patient with resolved HBV infection. Because hepatitis caused by HBV reactivation is more likely to become severe and makes the treatment of original diseases difficult, it is most important to prevent the onset of hepatitis. The basic strategy for prevention and treatment of HBV reactivation associated with powerful chemotherapy regimens should follow the guidelines for the management of hepatitis B virus infection by the Japan Society of Hepatology. Risk of HBV reactivation is determined by HBV infection status and the degree of immunosuppression. HBV infection status is classified into chronic active hepatitis, inactive carrier, and resolved infection. This corresponds, in descending order, to the risk of reactivation. Patients undergoing chemotherapy should be screened for HBV infection. HBsAg levels should be measured in all patients prior to commencement of treatment. In HBsAg-positive patients, HBeAg, anti-HBe antibody, and HBV DNA levels should also be measured. In HBsAg-negative patients, anti-HBc antibody and anti-HBs antibody should be measured. The next step for patients with resolved HBV infection is measurement of HBV DNA levels. In patients with resolved HBV infection whose HBV DNA level is 20 IU/mL or higher, as in inactive carriers, prophylactic therapy should be commenced before chemotherapy. In patients with resolved HBV infection whose HBV DNA level is less than 20 IU/mL, periodic monitoring of HBV DNA should be performed during and after chemotherapy. Preemptive therapy should be started immediately if the HBV DNA level ex- ceeds 20 IU/mL.


title: Short internal sequences involved in replication and virion accumulation in a subviral RNA of turnip crinkle virus.

text: cis-acting sequences and structural elements in untranslated regions of viral genomes allow viral RNA-dependent RNA polymerases to correctly initiate and transcribe asymmetric levels of plus and minus strands during replication of plus-sense RNA viruses. Such elements include promoters, enhancers, and transcriptional repressors that may require interactions with distal RNA sequences for function. We previously determined that a non-sequence-specific hairpin (M1H) in the interior of a subviral RNA (satC) associated with Turnip crinkle virus is required for fitness and that its function might be to bridge flanking sequences (X. Sun and A. E. Simon, J. Virol. 77:7880-7889, 2003). To establish the importance of the flanking sequences in replication and satC-specific virion repression, segments on both sides of M1H were randomized and subjected to in vivo functional selection (in vivo SELEX). Analyses of winning (functional) sequences revealed three different conserved elements within the segments that could be specifically assigned roles in replication, virion repression, or both. One of these elements was also implicated in the molecular switch that releases the 3' end from its interaction with the repressor hairpin H5, which is possibly involved in controlling the level of minus-strand synthesis.


title: Epidemiologic evaluation of diarrhea in dogs in an animal shelter.

text: OBJECTIVES To determine associations among infectious pathogens and diarrheal disease in dogs in an animal shelter and demonstrate the use of geographic information systems (GISs) for tracking spatial distributions of diarrheal disease within shelters. SAMPLE POPULATION Feces from 120 dogs. PROCEDURE Fresh fecal specimens were screened for bacteria and bacterial toxins via bacteriologic culture and ELISA, parvovirus via ELISA, canine coronavirus via nested polymerase chain reaction assay, protozoal cysts and oocysts via a direct fluorescent antibody technique, and parasite ova and larvae via microscopic examination of direct wet mounts and zinc sulfate centrifugation flotation. RESULTS Salmonella enterica and Brachyspira spp were not common, whereas other pathogens such as canine coronavirus and Helicobacter spp were common among the dogs that were surveyed. Only intestinal parasites and Campylobacterjejuni infection were significant risk factors for diarrhea by univariate odds ratio analysis. Giardia lamblia was significantly underestimated by fecal flotation, compared with a direct fluorescent antibody technique. Spatial analysis of case specimens by use of GIS indicated that diarrhea was widespread throughout the entire shelter, and spatial statistical analysis revealed no evidence of spatial clustering of case specimens. CONCLUSIONS AND CLINICAL RELEVANCE This study provided an epidemiologic overview of diarrhea and interacting diarrhea-associated pathogens in a densely housed, highly predisposed shelter population of dogs. Several of the approaches used in this study, such as use of a spatial representation of case specimens and considering multiple etiologies simultaneously, were novel and illustrate an integrated approach to epidemiologic investigations in shelter populations.