title: [Respiratory symptoms in meat pigs: is there a role for porcine respiratory corona virus (PRCV) and porcine reproductive and respiratory syndrome virus (PRRSV) in the etiology?].

text: On a pig farm with about 2000 pigs, respiratory problems regularly developed in fattening pigs 3 to 4 weeks after the start of the fattening period. A postmortem examination was carried out on four pigs during the acute phase of their illness. The animals showed signs of viral pneumonia. In two animals porcine respiratory virus (PRCV) was discovered and in the other two animals porcine reproductive and respiratory syndrome virus (PRRSV). The possible role of these two viruses in the aetiology of the health problems on this farm is discussed in the context of the results of a longitudinal serological study.


title: The geometric clutch as a working hypothesis for future research on cilia and flagella.

text: The Geometric Clutch hypothesis contends that the forces transverse to the flagellar axis (t-forces) act on the axonemal scaffold to regulate flagellar beating. T-forces develop as the product of the curvature and the accumulated tension or compression on the doublet microtubules. In this respect, t-force is a mediator of self-organizing behavior. It arises from the collective action of the assemblage of dynein motors on the structural components of the axoneme and, in turn, imparts order to the sequence of activation and deactivation of the dynein. At the switch point of the flagellar beat, the magnitude of the t-force per micron of flagellum is approximately equal to the sum total of dynein force that can be generated per micron of flagellum. This suggests that the t-force could directly overcome the force-producing dynein bridges and terminate their action. However, many questions remain to be answered concerning the behavior of the axonemal scaffold under stress. Little is known of the force-bearing capacity of the radial spokes and the central pair (cp) projections. The properties of these structures will determine how t-force is distributed within the axoneme. The mechanical and elastic properties of the dynein arms and nexin links need to be better understood to determine how they respond to the application of t-force. In the framework of the Geometric Clutch hypothesis these are the issues that are most important to explore if we are to understand how the flagellum works.


New and re-emerging infectious diseases.


title: A young infant with severe acute respiratory syndrome.

text: Severe acute respiratory syndrome (SARS), a new contagious respiratory disease associated with a novel coronavirus, has spread worldwide and become a global health concern after its first outbreak in Guangdong Province of the People's Republic of China in November 2002. The clinical presentation and the radiologic, hematologic, biochemical, and microbiologic findings of a 56-day-old male infant with SARS are described. Some clinical and laboratory features are similar to those reported in adult and pediatric patients. However, this infant had a more severe clinical course as compared with the older children. This is the youngest patient with symptomatic SARS reported to date.


title: The rationale of fever surveillance to identify patients with severe acute respiratory syndrome in Taiwan.

text: STUDY OBJECTIVE To establish a predictive scoring system and to determine its effectiveness for severe acute respiratory syndrome (SARS) cases confirmed by RT-PCR in patients with fever. METHODS A study was conducted of 484 consecutive patients seen in the emergency department (ED) of our tertiary care center during the SARS outbreak in Taiwan. The scoring system was divided into triage and screening station stages. Data were analysed with multivariable and logistic regression analysis. RESULTS Of 737 patients who presented to our ED for possible SARS from March to June 2003, we enrolled 484 patients with a temperature >38.0 degrees C (>100.3 degrees F) (age >18 years). Dyspnoea, diarrhoea, travel, close contact, hospital exposure, and household history were identified as predictive indicators in the triage stage. The triage score was the total of six items. With a one-point cutoff value, the sensitivity and specificity were 81.8% (18/22) and 73.6% (340/462). Leukocytosis, thrombocytopenia, lymphopenia, and CXR were identified as predictive indicators in the fever screening stage. Screening station scores (the sum of 10 items) consisted of triage scores, white blood cell count, and CXR. With a three-point cutoff value, the sensitivity and specificity were 95.5% (21/22) and 87.2% (403/462). CONCLUSIONS Syndromic and traditional surveillance play a role in early identification of SARS in an endemic area. The SARS scoring system described is easily applicable and highly effective in screening patients during outbreaks.


title: COVID-19, Negligence and Occupational Health and Safety: Ethical and Legal Issues for Hospitals and Health Centres.

text: The international incidence of health workers being infected with COVID-19 is deeply troubling. Until a vaccine is developed, they are the community's bulwark against the pandemic. It is vital that they be protected to the maximum extent possible. This entails the need for implementation of effective and compassionate protocols to keep their workplace as safe as possible for them, their colleagues and their patients in a context of much as yet not being known about the virus and awareness that some persons infected by it are for a time at least asymptomatic and that others test negative for it when they are prodromal or even already displaying some symptomatology. This has repercussions both for the liability of hospitals and multi-practitioner centres for negligence and also under occupational health and safety legislation. With the commencement of the roll out of biosecurity and disaster/emergency measures by government and escalating levels of anxiety in the general population, it is important to reflect upon the measures that most effectively can be adopted practically and ethically to protect the health and safety of those whose task it is to care for us if we become infected by COVID-19.


title: Evaluation of shell vial cell culture technique for the detection of bovine coronavirus.

text: The effect of blind passage and centrifugation on the isolation of bovine coronavirus in human rectal tumor cells cultured in shell vials was investigated. A total of 68 fecal samples known to be positive for bovine coronavirus by transmission electron microscopic (TEM) examination were used. The samples were centrifuged onto human rectal tumor cell monolayers and incubated in the presence of trypsin. The growth of bovine coronavirus in infected cells was demonstrated by fluorescent antibody staining, and the extracellular virus was detected and confirmed by hemagglutination and hemagglutination-inhibition tests, respectively. Of the 68 TEM-positive samples, 51 (75%), 58 (85%), and 61 (90%) grew in shell vial cell cultures at first, second, and third passages, respectively. Of the 51 cultures positive on first passage, 19 were examined by TEM; 18 of these were positive for bovine coronavirus. The shell vial technique was also compared with direct detection of bovine coronavirus by staining cryostat sections of infected tissues in a direct fluorescent antibody assay. The results of direct fluorescent antibody assay were available for 54 of the 68 samples, of which 53 (98%) and 43 (80%) were positive by shell vial technique and direct fluorescent antibody assay, respectively. For identification of bovine coronavirus, shell vials using human rectal tumor cells in the presence of trypsin is more sensitive than direct fluorescent antibody assay but is relatively less sensitive than transmission electron microscopy.


title: Validation of various osteoporosis risk indices in elderly Chinese females in Singapore.

text: INTRODUCTION This study aimed to compare the sensitivity and specificity of various published indices for identifying elderly Chinese females at risk of osteoporosis in Singapore. METHODS The indices considered were the Simple Calculated Osteoporosis Risk Estimation (SCORE), the Osteoporosis Risk Assessment Instrument (ORAI), the Age Bulk One or Never Estrogens (ABONE), body weight (WEIGHT), and the Osteoporosis Self-Assessment Tool for Asians (OSTA). Altogether, 135 postmenopausal Chinese female subjects aged 55 years and older participated in the study, and their bone mineral density (BMD) was measured with dual-energy x-ray absorptiometry. Subjects were classified as osteoporotic if their femoral neck BMD T-score was -2.5 or lower. Receiver operating characteristic (ROC) curves were generated to determine the indices' cut-off points, sensitivity, and specificity. RESULTS OSTA had the highest discriminatory power, with an estimated area under the ROC curve of 0.82. This was followed by SCORE (0.80), WEIGHT (0.78), ORAI (0.76), and ABONE (0.70). At the cut-off point of -2, OSTA achieved sensitivity and specificity of 91% and 59%, respectively. CONCLUSION The study showed that OSTA is an effective index for identifying postmenopausal women at risk for osteoporosis.


title: SOCS proteins in development and disease.

text: Cytokine and growth factor signaling mediates essential roles in the differentiation, proliferation, survival and function of a number of cell lineages. This is achieved via specific receptors located on the surface of target cells, with ligand binding activating key intracellular signal transduction cascades to mediate the requisite cellular outcome. Effective resolution of receptor signaling is also essential, with excessive signaling having the potential for pathological consequences. The Suppressor of cytokine signaling (SOCS) family of proteins represent one important mechanism to extinguish cytokine and growth factor receptor signaling. There are 8 SOCS proteins in mammals; SOCS1-7 and the alternatively named Cytokine-inducible SH2-containing protein (CISH). SOCS1-3 and CISH are predominantly associated with the regulation of cytokine receptor signaling, while SOCS4-7 are more commonly involved in the control of Receptor tyrosine kinase (RTK) signaling. Individual SOCS proteins are typically induced by specific cytokines and growth factors, thereby generating a negative feedback loop. As a consequence of their regulatory properties, SOCS proteins have important functions in development and homeostasis, with increasing recognition of their role in disease, particularly their tumor suppressor and anti-inflammatory functions. This review provides a synthesis of our current understanding of the SOCS family, with an emphasis on their immune and hematopoietic roles.


title: Gender and Age Differences Reveal Risk Patterns in COVID-19 Outbreak.

text: By April 28th 2020, the global number of people that were viciously infected with the newfound novel corona virus (COVID-19) stood at a staggering 3 077 133 cases, as per the confirmed data released by the WHO. It has been reported that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene. The level of ACE2 activity was very low in normal healthy younger persons, and was reported to be increased in patients with cardiovascular diseases. Thus, there might be severe myocarditis, that may result in acute heart failure and cardiac complexities in the elderly subjects.


title: Global perspectives on vaccine financing.

text: Despite the great promise of immunization and recent progress in immunizing children throughout the developing world, a global crisis in vaccine R&D, supply and delivery is faced. This article reviews how the global US6 billion dollars vaccine market is structured and its attractiveness to vaccine suppliers, the international two-tiered pricing system in which high-income countries generate about 82% of vaccine revenues but represent only 12% of the doses, the impact of schedule divergence as high-income and developing countries introduce different vaccines, the role of the US government, and possible approaches to ameliorate the crisis.


title: A third world international health elective for U.S. medical students: the 25-year experience of the State University of New York, Downstate Medical Center.

text: The Department of Preventive Medicine and Community Health at the State University of New York, Downstate Medical Center instituted a 6-8 weeks third world international health elective for fourth year medical students in 1980. Since that time, some 217 students have participated in a score of third world countries. However, the most popular sites have been India, Kenya and Thailand. The purposes of this elective are to provide fourth year medical students with an opportunity to observe and study the structure and functions of a health care delivery system in a third world country, to provide medical service, and to have a cross-cultural experience. The emphasis in this elective is on public health, preventive medicine and primary care. There are high levels of student competition for this elective. However, interest in it has been affected by world events such as the terrorist attacks of September 11, 2001 and the recent outbreak of Severe Acute Respiratory Syndrome (SARS) in Asia. Recent annual applications for this elective have been twenty-five and more out of a class of two hundred students. Annual acceptance rates vary considerably, ranging from as low as 27.2% in 1995-1996 to a high of 81.8% in 1987-1988. Careful screening, including an examination of academic records and personal interviews, has resulted in the selection of highly mature, adaptable, and dedicated students who overall have performed well at overseas sites. Student rated satisfaction levels with this elective are extremely high, with most rating it the best experience of their medical school years. Students undergo extensive preparation prior to going overseas. This includes individual health and safety issues, travel and lodging, and the nature of the host country culture, health care system, and assignment site. Our students are especially experienced in cross-cultural understanding because of the unusual diversity of the patients they treat in Brooklyn, and the ethnic diversity of local hospital staff and the medical school class. This Brooklyn experience in cross-cultural understanding has been cited by many participants as having been the best preparation for functioning in a foreign culture. In the late 1990s, we revised our procedures concerning health preparations so as to address the risk of HIV/AIDS and other blood borne diseases. In addition, we also adopted an Agreement and Release form containing 15 provisions requiring risk and responsibility assumption on the part of the student participants. The Alumni Fund of the College of Medicine has steadfastly supported this elective with both a philosophical commitment and financial grants to help defray travel costs. In 1998, Joshua H. Weiner of the class of 1941 created a sizeable endowment in the Alumni Fund of the College of Medicine to support students participating in this elective. In 2001, Sonja K. Binkhorst, Assistant Professor of Psychiatry at the Downstate Medical Center, arranged for some financial support for women medical students through the LSK Foundation and the American Medical Women's Association. During the years that this elective has been offered, overseas preceptors have willingly given of their time and institutional resources to make these experiences available and meaningful for students.


title: Site-directed mutagenesis of the Nidovirus replicative endoribonuclease NendoU exerts pleiotropic effects on the arterivirus life cycle.

text: The highly conserved NendoU replicative domain of nidoviruses (arteriviruses, coronaviruses, and roniviruses) belongs to a small protein family whose cellular branch is prototyped by XendoU, a Xenopus laevis endoribonuclease involved in nucleolar RNA processing. Recently, sequence-specific in vitro endoribonuclease activity was demonstrated for the NendoU-containing nonstructural protein (nsp) 15 of several coronaviruses. To investigate the biological role of this novel enzymatic activity, we have characterized a comprehensive set of arterivirus NendoU mutants. Deleting parts of the NendoU domain from nsp11 of equine arteritis virus was lethal. Site-directed mutagenesis of conserved residues exerted pleiotropic effects. In a first-cycle analysis, replacement of two conserved Asp residues in the C-terminal part of NendoU rendered viral RNA synthesis and virus production undetectable. In contrast, mutagenesis of other conserved residues, including two putative catalytic His residues that are absolutely conserved in NendoU and cellular homologs, produced viable mutants displaying reduced plaque sizes (20 to 80% reduction) and reduced yields of infectious progeny of up to 5 log units. A more detailed analysis of these mutants revealed a moderate reduction in RNA synthesis, with subgenomic RNA synthesis consistently being more strongly affected than genome replication. Our data suggest that the arterivirus nsp11 is a multifunctional protein with a key role in viral RNA synthesis and additional functions in the viral life cycle that are as yet poorly defined.


title: The In Vivo Skills Laboratory in Anesthesiology Residency Training.

text: BACKGROUND Anesthesiologists routinely perform high-risk procedures that are associated with permanent disability or death. Critical perioperative events require that the anesthesiologist perform procedures that are only used intermittently. Teaching these procedures is complicated by their infrequency and pressure to maximize operating room efficiency; therefore we created an annual 1-day anesthesiology skills lab as an innovative method of residency education. METHODS Anesthetized pigs served as the educational platform for first-year anesthesiology residents to gain hands-on experience performing regional, thoracic, vascular, and difficult airway techniques. A 20-question test was administered pre- and post-lab to assess the effectiveness of our educational intervention. Participants evaluated the quality of the educational experience (1-poor to 5-excellent). RESULTS First-year anesthesiology residents participated (n=70, 2008-2012). Residents' pre-test scores measured 50.3±2.6% (range 20-80). Following lab participation, their test scores signi ficantly improved to a mean of 84.2±1.9% (range 45-100, p<0.0001). Participants increased their knowledge and skills (mean 4.96±0.02), considered the skills lab to be a worthwhile educational experience (mean 4.99±0.01), and agreed that the lab should be repeated in the future (mean 5.00). CONCLUSIONS In vivo labs confers educational benefits which are both perceived and self-reported by the participants and objectively demonstrated by marked improvements in their post-test scores. Animal models provide high-fidelity tactile learning, real-time physiological changes, and potential for complications which builds residents' familiarity and confidence with anesthesiology-related procedures and crisis events that would otherwise involve potential patient risk. Our lab is an enriching and well-received educational tool which promotes our goal of improving patient safety.


title: Single-stitch telescopic bilioenterostomy in an animal model.

text: BACKGROUND/AIMS An end-to-side biliodigestive anastomosis is the most common procedure performed in hepato-pancreato-biliary surgery, and this procedure may become technically demanding. A telescopic ureterovesical anastomosis is frequently used in transplant surgery. The aim of this study was to investigate the feasibility of constructing a telescopic biliodigestive anastomosis. METHODOLOGY The technique-standardization (n = 8) and main study (n = 3) groups were formed from 11 pigs. A single-stitch telescopic anastomosis with a self-disposable internal stent was performed in the main study group. The animals were sacrificed at the end of the 4-week follow-up period, and cholangiograms and tissue samples were obtained. Repeated biological, hematological, and biochemical data were recorded. RESULTS No bilomas or functional biliary strictures were identified in any of the main study group animals. Light microscopy revealed intestinal metaplasia of the biliary epithelium in the portion of the bile duct telescoped inside the intestinal lumen. CONCLUSIONS Telescopic bilioenterostomy with a single pull-through stitch and a self-disposable stent is quick and reproducible in animal models, and it appears to be free of complications. Further experiments with longer follow-up periods are required to confirm that this anastomotic technique does not lead to episodes of delayed cholangitis or development of adenocarcinoma.


title: Urogynecologic conditions: chronic pelvic pain.

text: Immigration has brought millions of individuals into the United States over the past decade. The Centers for Disease Control and Prevention and the US Public Health Service are charged with ensuring that immigrants who enter do not pose a public health risk. Health examinations and immunization regimens are required for individuals wishing to live in the United States. Many immigrants and refugees are exposed to communicable diseases not routinely encountered in the United States These include helminthic infections, tuberculosis, malaria, and other infections. Zoonotic infections, such as influenza A, and novel coronavirus infections also are of increasing concern because of population mobility.


title: Kawasaki disease in England: ethnicity, deprivation, and respiratory pathogens.

text: BACKGROUND Kawasaki disease is now the commonest cause of acquired heart disease in children in the United Kingdom. Its incidence has increased in recent years. Epidemiologic analyses have provided insights into the possible etiology, but European data are scarce. METHODS We analyzed linked English-wide hospital admission data for Kawasaki disease in people younger than 18 years of age, during a 5-year period (1998-2003), relating incidence to geographic location, urbanization, deprivation, ethnicity, and to laboratory reports of respiratory infection. RESULTS There were 2432 admissions with Kawasaki disease in the study period for 1704 individuals. One thousand twenty-eight (60%) of the 1704 were male and 1228 (72%) were younger than 5 years of age. The annual age-specific incidence rate in those younger than 5 years was 8.39/100,000. Incidence rates in different areas of residence were significantly and independently related to both the degree of deprivation of the area and the proportion of the population in each area who were Chinese. After adjusting for the winter peaks in both the incidence of Kawasaki disease and respiratory virus infections, there was no correlation between Kawasaki disease and specific viruses. INTERPRETATION The previously reported increase in Kawasaki disease incidence in England has reached a plateau. These data support the concept of an infectious trigger in a genetically susceptible population, but known respiratory viral pathogens are unlikely to be the specific etiologic agents


title: Behavioral depression and positron emission tomography-determined serotonin 1A receptor binding potential in cynomolgus monkeys.

text: CONTEXT Current animal models of depression are inadequate to further our understanding of depression. New models that allow for analysis of cognitive function and sex differences are needed. OBJECTIVE To characterize serotonin 1A (5-HT(1A)) receptor binding potential (BP) and its relationship with specific characteristics of behavioral depression in cynomolgus monkeys. DESIGN A 23-month case-control study. SETTING Small social groups in the laboratory. Subjects Seventeen adult female cynomolgus monkeys. MAIN OUTCOME MEASURES Serotonin 1A receptor BP was examined by positron emission tomography using the radioligand 4,2"-(methoxyphenyl)-1-[2"-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine in the raphe, amygdala, hippocampus, and anterior cingulate cortex in monkeys characterized by behavioral observation as depressed or not depressed. Aggression, submission, affiliation, pathologic behaviors, and activity levels were determined by behavioral observation. Heart rate and hypothalamic-pituitary-adrenal function were also determined. RESULTS Throughout the brain areas examined, there was a reduction in 5-HT(1A) BP in depressed monkeys. The 5-HT(1A) BP in the amygdala and hippocampus was associated with aggression and submission. Friendly interaction, grooming, and locomotion were associated with 5-HT(1A) BP in the left cingulate cortex, whereas attention directed toward the environment was associated with 5-HT(1A) BP in the right cingulate cortex. The 5-HT(1A) receptor BP was inversely associated with heart rate in the raphe, left cingulate, and right amygdala. CONCLUSIONS This is the fourth in a series of studies that suggest that depressive behavior in adult female cynomolgus monkeys is similar to that observed in humans. It has been observed in 2 large groups of monkeys randomly selected from feral populations, suggesting that the capacity for depression is inherent in the species. This animal model holds promise to further our understanding of the basic mechanisms of affective behavior, the neuropathophysiologic characteristics of depression and the cognitive dysfunction that accompanies them, genetic and environmental factors that may affect depression risk, and the role of reproductive function in the excess depression risk in women.


Natural orifice transluminal endoscopic surgery (NOTES).


title: Bringing Cuban Biotech Research to Bear on COVID-19:All Hands and Minds on Deck.

text: This MEDICC Review roundtable gathers some of Cuba's top researchers in the fi elds of vaccines and biotechnology, all of whom work in institutions belonging to BioCubaFarma, the umbrella company of Cuban biotech and pharmaceutical R&D, production, distribution and export. Founded in 2012, the company is comprised of 34 enterprises with 61 lines of production and some 20,000 employees. A total of 765 of its products are registered in 53 countries and exported to an-other 50. Its scientists' research has resulted in 2640 patents in Cuba and globally.


title: Tooth resorption in the Swedish Eurasion lynx (Lynx lynx).

text: The etiology of tooth resorption in the domestic cat remains unknown. The high prevalence and progressive nature of the disease complicates defining healthy control groups. In order to evaluate the possible influence of various life style changes on the prevalence of tooth resorption, healthy control groups are a prerequisite. This paper presents a prevalence study for tooth resorption in a free-ranging wild felidae population. Skulls from 46 free-ranging Eurasian lynx (Lynx lynx) were examined. The age of the animals had previously been estimated based on cementum annuli in the maxillary right canine tooth. The dental examination included both dental probing and radiographic imaging. Complicated fractures of the canine teeth were found in 9/46 (19.5%) skulls. In one fractured canine, apical root resorption and periapical lucency was detected. The root resorption was attributed to inflammatory resorption as a consequence of the initial dental trauma and necrotic pulp. No signs of tooth resorption were found in the remaining teeth. Supernumerary roots were detected in 18/46 skulls (39.1 %). Supernumerary "peg" teeth caudal to the mandibular first molar tooth were detected in 6/46 (13.0%) skulls. Although further studies on dental ultra-structure are needed, the Swedish Eurasian lynx may, in the future, be useful as a healthy comparative model for studies on the etiopathogenesis of tooth resorption in the domestic cat.


title: The COVID-19 Pandemic and Paradigm Change in Global Scientific Research.

text: The current pandemic has rocked the lives of human beings every-where in ways never imagined, forcing us to question where our civilization is headed. In this article, we explore and discuss scien-tifi c evidence that helps explain recent events in the context of the COVID-19 pandemic.COVID-19 is caused by infection with a zoonotic-origin novel virus, SARS-CoV-2, that is genetically close to two coronavirus types iso-lated in bats. The transmission dynamics to humans from the original and intermediary hosts remain poorly understood, but it is highly likely that the SARS-CoV-2 virus infected humans after undergoing an inter-species transfer from bats to an intermediate species, and from there to human beings. Crossing the species barrier is largely fostered by industrial-scale agricultural practices that simplify original ecosystem connections by reducing biodiversity, facilitating the emergence of new infectious diseases. The scientifi c community has played an exemplary role in responding to this global emergency, working to fi nd timely, relevant solutions for governments and society as a whole. We need to take this opportunity to promote a global and open science that delves into the interrelation-ships of the biological, environmental, social and economic dimen-sions of this and other diseases while questioning current modes of production and their impact on the environment, and thus on human health worldwide. Keywords: Coronavirus infections; communicable diseases; zoonoses; ecosystems; technology, industry, and agriculture; pandemics; global health; Mexico.


title: Comparing McGRATH® MAC, C-MAC®, and Macintosh Laryngoscopes Operated by Medical Students: A Randomized, Crossover, Manikin Study.

text: We hypothesized that the McGRATH MAC would decrease the time of intubation compared to C-MAC for novices. Thirty-nine medical students who had used the Macintosh blade to intubate a manikin fewer than 3 times were recruited. The participants performed sequential intubations on the manikin in two simulated settings that included a normal airway and a difficult airway (tongue edema). The intubation time, success rate of intubation, Cormack-Lehane grade at laryngoscopy, and difficulty using the device were recorded. Each participant was asked to identify the device that was most useful. The intubation time decreased significantly and by a similar amount to the McGRATH MAC and C-MAC compared to the Macintosh blade (P < 0.001 and P = 0.017, resp.). In the difficult airway, the intubation times were similar among the three devices. The McGRATH MAC and C-MAC significantly increased the success rate of intubation, improved the Cormack-Lehane grade, and decreased the difficulty score compared to the Macintosh blade in both airway settings. The majority of participants selected the McGRATH MAC as the most useful device. The McGRATH MAC and C-MAC may offer similar benefits for intubation compared to the Macintosh blade in normal and difficult airway situations.


title: The human enteric coronaviruses.

text: A coronarirus was seen in the faeces from 15 (4.2%) of 355 adults with diarrhoea and from 5 (5.2%) of 96 adults without diarrhoea. Similar particles were seen in the faeces from 5 (2.2%) of 227 children aged 1--14 years with gastroenteritis, but in none of those from 230 infants under one year of age with gastroenteritis. There was no evidence that the coronavirus was responsible for any of 34 outbreaks of gastroenteritis, although it possibly caused diarrhoea in patients admitted to a psycho-geriatric unit. Excretion of the virus often continued for many months. One strain was propagated in human embryo kidney monolayers and human embryo intestinal organ cultures, although serial passage could not be accomplished.


Guideline for isolation precautions in hospitals.


title: ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis.

text: The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence. ACE2 has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). To gain further insights into this enzyme, the first crystal structures of the native and inhibitor-bound forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-A resolution, respectively. Comparison of these structures revealed a large inhibitor-dependent hinge-bending movement of one catalytic subdomain relative to the other ( approximately 16 degrees ) that brings important residues into position for catalysis. The potent inhibitor MLN-4760 ((S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol4-yl]-ethylamino]-4-methylpentanoic acid) makes key binding interactions within the active site and offers insights regarding the action of residues involved in catalysis and substrate specificity. A few active site residue substitutions in ACE2 relative to ACE appear to eliminate the S(2)' substrate-binding subsite and account for the observed reactivity change from the peptidyl dipeptidase activity of ACE to the carboxypeptidase activity of ACE2.


title: Coronavirus subgenomic minus-strand RNAs and the potential for mRNA replicons.

text: The genome of the porcine transmissible gastroenteritis coronavirus is a plus-strand, polyadenylylated, infectious RNA molecule of approximately 20 kilobases. During virus replication, seven subgenomic mRNAs are generated by what is thought to be a leader-priming mechanism to form a 3'-coterminal nested set. By using radiolabeled, strand-specific, synthetic oligodeoxynucleotide probes in RNA blot hybridization analyses, we have found a minus-strand counterpart for the genome and for each subgenomic mRNA species in the cytoplasm of infected cells. Subgenomic minus strands were found to be components of double-stranded replicative forms and in numbers that surpass full-length antigenome. We propose that subgenomic mRNA replication, in addition to leader-primed transcription, is a significant mechanism of mRNA synthesis and that it functions to amplify mRNAs. It is a mechanism of amplification that has not been described for any other group of RNA viruses. Subgenomic replicons may also function in a manner similar to genomes of defective interfering viruses to lead to the establishment of persistent infections, a universal property of coronaviruses.


title: Monoclonal antibody against non-dominant epitopes of HBV e Ag was raised by antigen-antibody co-immunization.

text: Detection of hepatitis B e antigen (HBeAg) in the sera of individuals infected with hepatitis B virus (HBV) can indicate both a high infectivity of the disease and a poor prognosis of disease treatment. Most of monoclonal antibodies raised against HBV e proteins interact with immuno-dominant epitopes, such as HBeAg-beta. In order to raise antibodies against non-dominant epitopes of HBV e protein, in this study, mice were immunized with both recombinant HBeAg (rHBeAg) and an anti-HBeAg antibody (EWB) recognizing a dominant antigenic epitope of HBeAg (HBeAg-beta epitope). With this strategy, we successfully selected two monoclonal antibodies, S-29-3 and S-72-3. Both S-29-3 and S-72-3 bind to recombinant HBeAg with a high affinity. The epitope mapping assay determined that the S-73-2 recognizes the N-terminal of HBeAg (1-118 aa) and the S-29-3 recognizes the C-terminal of HBeAg (91-149 aa). Further experiment showed that these two antibodies could be formed a pair-Abs that is used in detecting native HBeAg from the sera of HBV patients. The conclusion is that the developed method is useful to raise mAb against non-dominant epitopes in given Ag.


title: Determination of lactose and xylose malabsorption in preruminant diarrheic calves.

text: In preliminary studies feeding the poorly absorbed carbohydrate sorbitol at 2.3 g/kg body weight as an indication of maximal fermentative capacity failed to produce the expected large increase in breath hydrogen excretion but did produce a transient diarrhea in five out of six control calves. Twelve healthy control and eighteen diarrheic calves were fed lactose or D-xylose on consecutive days at 1.15 g/kg body weight and a concentration of 46 g/L. Breath and blood samples were collected at 1 h intervals from 0 to 7 h. After administration of lactose, there was a significant increase in breath hydrogen excretion in diarrheic versus control calves. The increase in plasma glucose concentrations was delayed in diarrheic calves but the area under the absorption curve was similar in control and diarrheic calves. After administration of D-xylose, breath hydrogen excretion did not increase significantly but plasma D-xylose concentrations were significantly reduced in diarrheic calves. The pathogens commonly isolated from the feces were Cryptosporidium species, rotavirus and coronavirus. The number of pathogens and the severity of the calves' acid-base deficit were not related to the severity of carbohydrate malabsorption. Decreased absorption of lactose and D-xylose may be the result of intestinal villous atrophy caused by viral or parasite infection. It was concluded that carbohydrate malabsorption rather than a specific lactose maldigestion is a significant problem in diarrheic calves. Diarrheic calves appear to digest and absorb lactose when fed in small amounts.


title: NK cells contribute to intracellular bacterial infection-mediated inhibition of allergic responses.

text: To experimentally examine the hygiene hypothesis, here we studied the effect of chlamydial infection on the development of allergic responses induced by OVA and the involvement of NK cells in this process using a mouse model of airway inflammation. We found that prior Chlamydia muridarum infection can inhibit airway eosinophilic inflammation and mucus production induced by allergen sensitization and challenge. The inhibition was correlated with an alteration of allergen-driven cytokine-producing patterns of T cells. We demonstrated that NK cells were activated following chlamydial infection, showing both cell expansion and cytokine secretion. The in vivo depletion of NK cells using anti-NK Ab before OVA sensitization and challenge partially abolished the inhibitory effect of chlamydial infection, which was associated with a partial restoration of Th2 cytokine production. In contrast, the adoptive transfer of NK cells that were isolated from infected mice showed a significant inhibitory effect on allergic responses, similar to that observed in natural infection. The data suggest that the innate immune cells such as NK cells may play an important role in infection-mediated inhibition of allergic responses.


title: Internal ribosome entry in the coding region of murine hepatitis virus mRNA 5.

text: The unique region of murine hepatitis virus (MHV) mRNA 5 has two open reading frames. ORF 5a and ORF 5b, that encode small proteins of unknown function. In the experiments described here, we have used the in vitro translation of synthetic mRNAs to examine the expression of these ORFs. Our results show that a synthetic mRNA containing both ORFs is functionally bicistronic. More importantly, the expression of ORF 5b, but not ORF 5a, is maintained in a tricistronic mRNA containing an additional 5'-proximal ORF. Thus, in the context of the MHV mRNA 5 unique region, the initiation of protein synthesis on ORF 5b can occur independently of ribosomes that enter from the 5' end of the mRNA. We conclude that the translation of ORF 5b is mediated by the internal entry of ribosomes.


FELASA recommendations for the health monitoring of experimental units of calves, sheep and goats Report of the federation of European Laboratory Animal Science Associations (FELASA) Working Group on Animal Health.


title: Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies.

text: To analyze the pathogenesis of the neurotropic murine coronavirus JHMV, we used monoclonal antibodies to the E2 viral glycoprotein to select antigenic variant viruses. Monoclonal antibodies J.7.2 and J.2.2 were shown to bind to topographically distinct regions of the E2 molecule, and the variants selected with the two antibodies demonstrated very different disease pictures in mice. Variants selected with J.7.2 were, like the parental virus, highly virulent and caused an acute encephalitic illness. By contrast, J.2.2-selected variants predominantly caused a subacute paralytic disease clinically and extensive demyelination histologically. Antigenic differences among the variants and parental virus were readily demonstrable with anti-E2 monoclonal antibodies. However, no differences between the viruses could be shown in binding studies with monoclonal antibodies directed against either E1 or N, the other two JHMV structural proteins. Since only J.2.2 selected demyelinating variants with reduced neurovirulence, it is likely that this monoclonal antibody recognizes a subregion of the E2 molecule that is particularly important in JHMV pathogenesis.


title: Pathogen-specific recombinant human polyclonal antibodies: biodefence applications.

text: The potential use of biological agents such as viruses, bacteria or bacterial toxins as weapons of mass destruction has fuelled significant national and international research and development in novel prophylactic or therapeutic countermeasures. Such measures need to be fast-acting and broadly specific, a hallmark of target-specific polyclonal antibodies (pAbs). As reviewed here, pathogen-specific antibodies in the form of human or animal serum have long been recognised as effective therapies in a number of infectious diseases. This review focuses in particular on the potential biowarfare agents prioritised by the National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention (CDC), referred to as the category A organisms. Furthermore, it is propose that the last decade of development in recombinant antibody technologies offers the possibility for developing highly specific human monoclonal or polyclonal pathogen-specific antibodies. In particular, pathogen-specific polyclonal human antibodies offer certain advantages over existing hyperimmune serum products, monoclonal antibodies, small molecule drugs and vaccines. Here, the rationale for designing pAb-based therapeutics against the CDC category A microbial agents causing anthrax, botulism, plague, smallpox, tularaemia and viral haemorrhagic fevers, as well as the overall design of such therapeutics, are discussed.


Vitamin D and Covid-19: A Note of Caution.


title: Treatment Planning for Image-Guided Neuro-Vascular Interventions Using Patient-Specific 3D Printed Phantoms.

text: Minimally invasive endovascular image-guided interventions (EIGIs) are the preferred procedures for treatment of a wide range of vascular disorders. Despite benefits including reduced trauma and recovery time, EIGIs have their own challenges. Remote catheter actuation and challenging anatomical morphology may lead to erroneous endovascular device selections, delays or even complications such as vessel injury. EIGI planning using 3D phantoms would allow interventionists to become familiarized with the patient vessel anatomy by first performing the planned treatment on a phantom under standard operating protocols. In this study the optimal workflow to obtain such phantoms from 3D data for interventionist to practice on prior to an actual procedure was investigated. Patient-specific phantoms and phantoms presenting a wide range of challenging geometries were created. Computed Tomographic Angiography (CTA) data was uploaded into a Vitrea 3D station which allows segmentation and resulting stereo-lithographic files to be exported. The files were uploaded using processing software where preloaded vessel structures were included to create a closed-flow vasculature having structural support. The final file was printed, cleaned, connected to a flow loop and placed in an angiographic room for EIGI practice. Various Circle of Willis and cardiac arterial geometries were used. The phantoms were tested for ischemic stroke treatment, distal catheter navigation, aneurysm stenting and cardiac imaging under angiographic guidance. This method should allow for adjustments to treatment plans to be made before the patient is actually in the procedure room and enabling reduced risk of peri-operative complications or delays.


Effective mucus clearance is essential for respiratory health.


Molecular virology.


title: Enteric infections in veal calves: a longitudinal study on four veal calf units.

text: Forty-five calves on four veal calf units were monitored during the first four weeks after their arrival. Faecal samples were collected on alternate days and screened for the presence of rotaviruses, bovine coronavirus, Cryptosporidium oocysts, K99 positive strains of E. coli and Salmonella spp. Rotaviruses and Cryptosporidium were the most commonly detected agents (78% and 60% respectively of the calves). Bovine coronavirus was detected in the faeces of 18% of the calves, whilst K99 positive E. coli was only found in 2 samples from one calf. Salmonella spp. were not isolated from any of the 646 faecal samples examined. Shedding of rotaviruses occurred in a bimodal pattern beginning in the first week of the survey. Cryptosporidium oocysts were detected most frequently in the interval between the two peaks of rotavirus shedding. The presence of rotaviruses or Cryptosporidium oocysts in faeces was not strongly associated with scour, nor were combined infections with these agents or the cases of bovine coronavirus infection. The condition of the calves throughout the survey was generally satisfactory.


title: X-ray crystallographic structure of the Norwalk virus protease at 1.5-A resolution.

text: Norwalk virus (NV), a member of the Caliciviridae family, is the major cause of acute, epidemic, viral gastroenteritis. The NV genome is a positive sense, single-stranded RNA that encodes three open reading frames (ORFs). The first ORF produces a polyprotein that is processed by the viral cysteine protease into six nonstructural proteins. We have determined the structure of the NV protease to 1.5 and 2.2 A from crystals grown in the absence or presence, respectively, of the protease inhibitor AEBSF [4-(2-aminoethyl)-benzenesulfonyl fluoride]. The protease, which crystallizes as a stable dimer, exhibits a two-domain structure similar to those of other viral cysteine proteases with a catalytic triad composed of His 30, Glu 54, and Cys 139. The native structure of the protease reveals strong hydrogen bond interactions between His 30 and Glu 54, in the favorable syn configuration, indicating a role of Glu 54 during proteolysis. Mutation of this residue to Ala abolished the protease activity, in a fluorogenic peptide substrate assay, further substantiating the role of Glu 54 during proteolysis. These observations contrast with the suggestion, from a previous study of another norovirus protease, that this residue may not have a prominent role in proteolysis (K. Nakamura, Y. Someya, T. Kumasaka, G. Ueno, M. Yamamoto, T. Sato, N. Takeda, T. Miyamura, and N. Tanaka, J. Virol. 79:13685-13693, 2005). In the structure from crystals grown in the presence of AEBSF, Glu 54 undergoes a conformational change leading to disruption of the hydrogen bond interactions with His 30. Since AEBSF was not apparent in the electron density map, it is possible that these conformational changes are due to subtle changes in pH caused by its addition during crystallization.


Handwashing precautions taken by renal transplant recipients for severe acute respiratory syndrome.


title: A point mutation within the replicase gene differentially affects coronavirus genome versus minigenome replication.

text: During the construction of the transmissible gastroenteritis virus (TGEV) full-length cDNA clone, a point mutation at position 637 that was present in the defective minigenome DI-C was maintained as a genetic marker. Sequence analysis of the recovered viruses showed a reversion at this position to the original virus sequence. The effect of point mutations at nucleotide 637 was analyzed by reverse genetics using a TGEV full-length cDNA clone and cDNAs from TGEV-derived minigenomes. The replacement of nucleotide 637 of TGEV genome by a T, as in the DI-C sequence, or an A severely affected virus recovery from the cDNA, yielding mutant viruses with low titers and small plaques compared to those of the wild type. In contrast, T or A at position 637 was required for minigenome rescue in trans by the helper virus. No relationship between these observations and RNA secondary-structure predictions was found, indicating that mutations at nucleotide 637 most likely had an effect at the protein level. Nucleotide 637 occupies the second codon position at amino acid 108 of the pp1a polyprotein. This position is predicted to map in the N-terminal polyprotein papain-like proteinase (PLP-1) cleavage site at the p9/p87 junction. Replacement of G-637 by A, which causes a drastic amino acid change (Gly to Asp) at position 108, affected PLP-1-mediated cleavage in vitro. A correlation was found between predicted cleaving and noncleaving mutations and efficient virus rescue from cDNA and minigenome amplification, respectively.


Update in infectious diseases.


Vaccines in travel health: from risk assessment to priorities.


title: Circulating Tumour Cells in Patients with Malignant Lung Tumors Undergoing Radio-frequency Ablation.

text: BACKGROUND/AIM Radiofrequency ablation (RFA) is an increasingly utilised technique in patients with surgically-untreatable lesions. The effect of this therapy on circulating tumor cells (CTCs) is unknown. As far as we are aware of, this is the first study to evaluate the effects of RFA on CTCs in patients with malignant lung tumors immediately post-treatment. PATIENTS AND METHODS Nine patients with primary or metastatic lung tumors underwent RFA therapy from June to November 2013. Blood samples were taken before and after RFA, and filtered through the ScreenCell CTC capture device. RESULTS A general increase in CTCs in 7 out of the 9 cases was found, the largest increases were seen in the metastatic group. CONCLUSION This study demonstrates that the manipulation and ablative procedure of lung tumors leads to immediate dissemination of tumor cells, the effects of which are unknown and require further investigation.


title: [Clinical presentation and management of the severe acute respiratory syndrome (SARS)].

text: BACKGROUND AND OBJECTIVE In February 2003, a newly emerged infectious disease was described, the etiology of which was initially unknown. It is referred to under the term SARS. In the beginning, it spread in some regions South-East Asia. Import infections appeared in many other parts of the world. Based on the first cases in Germany, this report illustrates the clinical appearance, the diagnostic results and the management of this new disease. PATIENTS AND METHODS We analysed the data of two patients with SARS and one suspected patient. The results of radiological, laboratory, microbiological and physical examinations were abstracted and compared with the data obtained in other regions. RESULTS Two of the three patients under our care developed SARS disease. This is characterised by fever of sudden onset lasting for more than 5 days, rapidly changing consolidations in chest x-ray not affected by antimicrobial therapy, leuko-, lympho- as well as thrombopenia with a compromised pulmonary function later in the course. Close contacts with SARS patients does not regularly result in full development of the disease. Secretion of a coronavirus could be detected in respiratory samples during the febrile phase and in feces for a longer time. It is still an open question whether bedrest and antibiotic prophylaxis by themselves or an additional administration of ribavirin and corticosteroids can improve the outcome. CONCLUSION SARS is a new and highly contagious lung disease. It is crucial to be able to recognize the clinical appearance and the diagnostic features of this disease at an early stage, in order to prevent a further dissemination of the disease.


title: NEPHROPATHIES IN THE EUROPEAN CAPTIVE CHEETAH (ACINONYX JUBATUS) POPULATION.

text: According to previous studies in captive cheetah ( Acinonyx jubatus ) populations, one of the most threatening diseases besides amyloidosis, myelopathy, veno occlusive disease, and gastritis, is renal failure. Contrary to captive cheetahs in North America and South Africa, morphological data concerning renal lesions in the cheetah European Endangered Species Program (EEP) are lacking. This study details the histological characterization as well as immunohistochemical and morphometrical analysis of nephropathies in 35 captive cheetahs from the EEP, which were necropsied between 1985 and 2003. Examination of paraffin- and glycolmethacrylate-methylmethacrylate (GMA-MMA) embedded kidney samples by light microscopy revealed glomerulonephritis in 91%, with a high prevalence for glomerulosclerosis and glomerulonephritis with the histologic pattern of membranous glomerulonephritis (77%). Besides these predominating glomerulopathies, a wide range of other renal lesions, like acute tubular necrosis, interstitial nephritis, calcinosis, and amyloidosis, were present. Pathological expression of collagen type IV, complement C3, fibronectin, and IgG was demonstrated in the glomeruli of the cheetah kidneys with the use of the avidin-biotin complex method. Morphometrical analysis was performed on GMA-MMA embedded kidney samples to obtain glomerulosclerosis index and glomerulosclerosis incidence.


title: Environmental transmission of SARS at Amoy Gardens.

text: Recent investigations into the March 2003 outbreak of SARS in Hong Kong have concluded that environmental factors played an important role in the transmission of the disease. These studies have focused on a particular outbreak event, the rapid spread of SARS throughout Amoy Gardens, a large, private apartment complex. They have demonstrated that, unlike a typical viral outbreak that is spread through person-to-person contact, the SARS virus in this case was spread primarily through the air. High concentrations of viral aerosols in building plumbing were drawn into apartment bathrooms through floor drains. The initial exposures occurred in these bathrooms. The virus-laden air was then transported by prevailing winds to adjacent buildings at Amoy Gardens, where additional exposures occurred. This article reviews the results of the investigations and provides recommendations for maintenance and other measures that building owners can take to help prevent environmental transmission of SARS and other flulike viruses in their buildings.


title: Effects of Static and Dynamic Stretching on the Isokinetic Peak Torques and Electromyographic Activities of the Antagonist Muscles.

text: The aim of this study was to investigate if static and dynamic stretching exercises of the knee muscles (quadriceps and hamstring muscles) have any effects on concentric and eccentric isokinetic peak torques and electromyographic amplitudes (EMG) of the antagonist muscles. Twenty healthy male athletes (age between 18-30 years) voluntarily participated in this study. All of the subjects visited the laboratory to complete the following intervention in a randomized order on 5 separate days; (a) non-stretching (control), (b) static stretching of the quadriceps muscles, (c) static stretching of the hamstring muscles, (d) dynamic stretching of the quadriceps muscles, and (e) dynamic stretching of the hamstring muscles. Static stretching exercises either for the quadriceps or the hamstring muscles were carried out at the standing and sitting positions. Subjects performed four successive repetitions of each stretching exercises for 30 seconds in both stretching positions. Similar to static stretching exercises two different stretching modes were designed for dynamic stretching exercises. Concentric and eccentric isokinetic peak torque for the non-stretched antagonist quadriceps or hamstring muscles at angular velocities of 60°/sec and 240°/sec and their concurrent electromyographic (EMG) activities were measured before and immediately after the intervention. Isokinetic peak torques of the non-stretched agonist hamstring and quadriceps muscles did not represent any significant (p > 0.05) differences following static and dynamic stretching of the antagonist quadriceps and hamstring muscles, respectively. Similarly, the EMG activities of the agonist muscles exhibited no significant alterations (p > 0.05) following both stretching exercises of the antagonist muscles. According to the results of the present study it is possible to state that antagonist stretching exercises either in the static or dynamic modes do not affect the isokinetic peak torques and the EMG activities of the non-stretched agonist quadriceps or hamstring muscles.


title: Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide.

text: Antiviral agents are urgently needed to fight severe acute respiratory syndrome (SARS). We showed that niclosamide, an existing antihelminthic drug, was able to inhibit replication of a newly discovered coronavirus, SARS-CoV; viral antigen synthesis was totally abolished at a niclosamide concentration of 1.56 microM, as revealed by immunoblot analysis. Thus, niclosamide represents a promising drug candidate for the effective treatment of SARS-CoV infection.


SARS in China. The big question now: will it be back?


title: Comparative estimation of the reproduction number for pandemic influenza from daily case notification data.

text: The reproduction number, R, defined as the average number of secondary cases generated by a primary case, is a crucial quantity for identifying the intensity of interventions required to control an epidemic. Current estimates of the reproduction number for seasonal influenza show wide variation and, in particular, uncertainty bounds for R for the pandemic strain from 1918 to 1919 have been obtained only in a few recent studies and are yet to be fully clarified. Here, we estimate R using daily case notifications during the autumn wave of the influenza pandemic (Spanish flu) in the city of San Francisco, California, from 1918 to 1919. In order to elucidate the effects from adopting different estimation approaches, four different methods are used: estimation of R using the early exponential-growth rate (Method 1), a simple susceptible-exposed-infectious-recovered (SEIR) model (Method 2), a more complex SEIR-type model that accounts for asymptomatic and hospitalized cases (Method 3), and a stochastic susceptible-infectious-removed (SIR) with Bayesian estimation (Method 4) that determines the effective reproduction number Rt at a given time t. The first three methods fit the initial exponential-growth phase of the epidemic, which was explicitly determined by the goodness-of-fit test. Moreover, Method 3 was also fitted to the whole epidemic curve. Whereas the values of R obtained using the first three methods based on the initial growth phase were estimated to be 2.98 (95% confidence interval (CI): 2.73, 3.25), 2.38 (2.16, 2.60) and 2.20 (1.55, 2.84), the third method with the entire epidemic curve yielded a value of 3.53 (3.45, 3.62). This larger value could be an overestimate since the goodness-of-fit to the initial exponential phase worsened when we fitted the model to the entire epidemic curve, and because the model is established as an autonomous system without time-varying assumptions. These estimates were shown to be robust to parameter uncertainties, but the theoretical exponential-growth approximation (Method 1) shows wide uncertainty. Method 4 provided a maximum-likelihood effective reproduction number 2.10 (1.21, 2.95) using the first 17 epidemic days, which is consistent with estimates obtained from the other methods and an estimate of 2.36 (2.07, 2.65) for the entire autumn wave. We conclude that the reproduction number for pandemic influenza (Spanish flu) at the city level can be robustly assessed to lie in the range of 2.0-3.0, in broad agreement with previous estimates using distinct data.


title: Role of surfactant protein A and D (SP-A and SP-D) in human antiviral host defense.

text: SP-A and SP-D contribute to host defense against respiratory viral infection. The most extensive body of evidence relates to influenza A viruses (IAV), and evidence from gene-deleted mice also indicate a role for surfactant collectins in defense against respiratory syncytial virus (RSV) and adenovirus. Some important respiratory pathogens including rhinovirus and metapneumovirus have not yet been examined. Viral pathogens that enter the body via the respiratory tract (e.g., Ebola virus), replicate in the lung (e.g., human immunodeficiency virus or HIV) or infect the lung in immuno-compromised hosts (e.g., herpes simplex virus or HSV) are inhibited by collectins. SP-A and SP-D are expressed in other mucosal surfaces (e.g., the eye or genitourinary tract) where they may play roles in antiviral defense. In addition to direct antiviral activities, the SP-A and SP-D modulate innate and adaptive immunity and inflammation associated with infection. The relative importance of antiviral vs anti-inflammatory effects of SP-A and SP-D in viral infections and the potential use of these collectins as therapeutics for viral infections are under investigation.


title: Sustainable control of zoonotic pathogens in wildlife: how to be fair to wild animals?

text: Wildlife may harbour infectious pathogens that are of zoonotic concern. However, culling such reservoir populations to mitigate or control the transmission of these pathogens to humans has proved disappointingly inefficient. Alternatives are still in an experimental stage of development. They include vaccination, medication, contraception and environmental manipulation, including fencing and biosecurity measures. This review examines the general concepts involved in the control of wildlife diseases and presents relevant case studies. Since wildlife disease control inevitably involves interfering with wildlife ecology, this is a complex goal whose attempts at realisation should be supervised by a scientific organisation. Most approaches within natural ecosystems should first be carefully tested in trials that are progressively extended to a larger scale. Finally, all measures that aim to prevent infection in humans (such as personal hygiene or vaccination) or that encourage us to avoid infectious contacts with wildlife should be recommended.


title: Stability of extemporaneous oral ribavirin liquid preparation.

text: Ribavirin is an antiviral agent commonly used in Hong Kong for the treatment of severe acute respiratory syndrome. The choice of oral ribavirin therapeutic products available in the local market is currently limited to capsules. The present study investigated the chemical stability of an oral ribavirin suspension (200 mg/5mL) prepared extemporaneously from oral capsules using a sugar-free suspension formula. The suspension was subjected to stability testing at 4 deg C for up to 28 days. Employing a validated stability-indicating high-performance liquid chromatographic method, the ribavirin content of the extemporaneous preparation has been demonstrated to exhibit negligible changes throughout the storage period. No degradation product was observable in all high-peroformance liquid chromatograms, suggesting that the suspension remained chermically stable under the stated conditions.


title: Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus.

text: Positive-strand RNA viruses are the largest virus class and include many pathogens such as hepatitis C virus and the severe acute respiratory syndrome coronavirus (SARS). Brome mosaic virus (BMV) is a representative positive-strand RNA virus whose RNA replication, gene expression, and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. By using traditional yeast genetics, host genes have been identified that function in controlling BMV translation, selecting BMV RNAs as replication templates, activating the replication complex, maintaining a lipid composition required for membrane-associated RNA replication, and other steps. To more globally and systematically identify such host factors, we used engineered BMV derivatives to assay viral RNA replication in each strain of an ordered, genome-wide set of yeast single-gene deletion mutants. Each deletion strain was transformed to express BMV replicase proteins and a BMV RNA replication template with the capsid gene replaced by a luciferase reporter. Luciferase expression, which is dependent on viral RNA replication and RNA-dependent mRNA synthesis, was measured in intact yeast cells. Approximately 4500 yeast deletion strains ( approximately 80% of yeast genes) were screened in duplicate and selected strains analyzed further. This functional genomics approach revealed nearly 100 genes whose absence inhibited or stimulated BMV RNA replication and/or gene expression by 3- to >25-fold. Several of these genes were shown previously to function in BMV replication, validating the approach. Newly identified genes include some in RNA, protein, or membrane modification pathways and genes of unknown function. The results further illuminate virus and cell pathways. Further refinement of virus screening likely will reveal contributions from additional host genes.


title: Organizational capacity for community development in regional health authorities: a conceptual model.

text: The value of community development (CD) practices is well documented in the health promotion literature; it is a foundational strategy outlined in the Ottawa Charter for Health Promotion. Despite the importance of collaborative action with communities to enhance individual and community health and well-being, there exists a major gap between the evidence for CD and the actual extent to which CD is carried out by health organizations. In this paper it is argued that the gap exists because we have failed to turn the evaluative gaze inward-to examine the capacity of health organizations themselves to facilitate CD processes. This study was designed to explicate key elements that contribute to organizational capacity for community development (OC-CD). Twenty-two front-line CD workers and managers responsible for CD initiatives from five regional health authorities in Alberta, Canada, were interviewed. Based on the study findings, a multidimensional model for conceptualizing OC-CD is presented. Central to the model are four inter-related dimensions: (i) organizational commitment to CD, rooted in particular values and beliefs, leadership and shared understanding of CD; (ii) supportive structures and systems, such as job design, flexible planning processes, evaluation mechanisms and collaborative processes; (iii) allocation of resources for CD; and (iv) working relationships and processes that model CD within the health organization. These four dimensions contribute to successful CD practice in numerous ways, but perhaps most importantly by supporting the empowerment and autonomy of the pivotal organizational player in health promotion practice: the front-line worker.


title: Novel antiviral agents: a medicinal plant perspective.

text: Several hundred plant and herb species that have potential as novel antiviral agents have been studied, with surprisingly little overlap. A wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins and peptides have been identified. Some volatile essential oils of commonly used culinary herbs, spices and herbal teas have also exhibited a high level of antiviral activity. However, given the few classes of compounds investigated, most of the pharmacopoeia of compounds in medicinal plants with antiviral activity is still not known. Several of these phytochemicals have complementary and overlapping mechanisms of action, including antiviral effects by either inhibiting the formation of viral DNA or RNA or inhibiting the activity of viral reproduction. Assay methods to determine antiviral activity include multiple-arm trials, randomized crossover studies, and more compromised designs such as nonrandomized crossovers and pre- and post-treatment analyses. Methods are needed to link antiviral efficacy/potency- and laboratory-based research. Nevertheless, the relative success achieved recently using medicinal plant/herb extracts of various species that are capable of acting therapeutically in various viral infections has raised optimism about the future of phyto-antiviral agents. As this review illustrates, there are innumerable potentially useful medicinal plants and herbs waiting to be evaluated and exploited for therapeutic applications against genetically and functionally diverse viruses families such as Retroviridae, Hepadnaviridae and Herpesviridae


title: Inhibition of SARS coronavirus helicase by bismuth complexes.

text: A series of bismuth complexes were synthesized and characterized, and most of them exhibited inhibition against the SARS coronavirus helicase ATPase and duplex-unwinding activities at micromolar concentrations.


title: Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries.

text: Many tissues including blood, skin, gut and germ cells are continuously maintained by tissue stem cells. Under certain conditions, however, other organs can undergo repair using stem-cell-like progenitors generated by cell de-differentiation. Cell fates have been broadened experimentally, but mechanisms allowing de-differentiation to a stem cell state are poorly known. Germline stem cells begin to differentiate by forming interconnected germ cell cysts (cystocytes), and under certain conditions male mouse cystocytes have been postulated to revert into functional progenitors. Here we report that four- and eight-cell Drosophila germline cystocytes generated either in second instar larval ovaries or in adults over-producing the BMP4-like stem cell signal Decapentaplegic efficiently convert into single stem-like cells. These de-differentiated cells can develop into functional germline stem cells and support normal fertility. Our results show that cystocytes represent a relatively abundant source of regenerative precursors that might help replenish germ cells after depletion by genotoxic chemicals, radiation or normal ageing. More generally, Drosophila cystocytes now provide a system for studying de-differentiation and its potential as a source of functional stem cells.


title: A study of RFID application impacts on medical safety.

text: With the international reform in medical management systems gaining ground worldwide, hospital management has gradually begun to shift its focus from providing expensive medical treatment to improving medical service quality and patient safety. In this study, we discuss the application of Radio Frequency Identification (RFID) and data integrating technology with the medical service, and examine whether or not this technology can enhance medical safety. We also discuss the possible benefits following the application of the RFID system. The findings show that the application of RFID to hospitals can actually generate benefits, which can be further divided into operational structure benefits, users' structure benefits, and organisational and environmental benefits. However, not all these benefits can achieve medical safety. Among them, only the operator and environmental benefits can play such roles. Nevertheless, the application of RFID can bring hospitals towards the integration of technology benefits and improved medical safety.


title: A new nucleotide-composition based fingerprint of SARS-CoV with visualization analysis.

text: It has been observed by conducting an extensive analysis of the two-dimensional cellular automata images of known SARS-CoV genome sequences that the V-shaped cross-lines only exist in some special locations, and hence can be used as a fingerprint to identify the SARS sequences. Such a discovery can be used to rapidly and reliably diagnose SARS coronavirus for both basic research in laboratories and practical application in clinics.


title: Host intraspatial selection of infectious bronchitis virus populations.

text: Arkansas (Ark)-type infectious bronchitis virus (IBV) subpopulations with an S gene sequence distinct from the vaccine predominant consensus were previously found in the upper respiratory tract of chickens within 3 days after inoculation. This finding indicated that a distinct virus subpopulation was rapidly positively selected by the chicken upper respiratory tract. We hypothesized that during host invasion, the replicating IBV population further changes as it confronts the distinct environments of different tissues, leading to selection of the most fit population. We inoculated 15-day-old chickens with 10(4) 50% embryo infective doses of an Ark-type IBV commercial vaccine via the ocular and nasal routes and characterized the sequences of the S1 gene of IBV contained in tear fluid, trachea, and reproductive tract of individual chickens at different times postinoculation. The predominant IBV phenotype contained in the vaccine (before inoculation) became a minor or nondetectable population at all times in all tissues after replication in the majority of the chickens, corroborating our previous findings. Five new predominant populations designated component (C) 1 through C5, showing distinct nonsynonymous changes, i.e., nucleotide changes resulting in different amino acids encoded and thus in a phenotypic change of the predominant virus population, were detected in the tissues or fluids of individual vaccinated chickens. Due to the different biochemical properties of some amino acids that changed in the S1 glycoprotein, we anticipate that phenotypic shift occurred during the invasion process. Significant differences were detected in the incidence of some distinct IBV predominant populations in tissues and fluids; e.g., phenotype C1 showed the highest incidence in the reproductive tract of the chickens, achieving a significant difference versus its incidence in the trachea (P < 0.05). These results indicate for the first time that IBV undergoes intraspatial variation during host invasion, i.e., the dominant genotype/phenotype further changes during host invasion as the microenvironment of distinct tissues exerts selective pressure on the replicating virus population.


title: [Preliminary result on the nosocomial infection of severe acute respiratory syndrome in one hospital of Beijing].

text: OBJECTIVE To study the transmission route of severe acute respiratory syndrome (SARS) nosocomial infection. METHODS Ten identified SARS patients were selected from a general hospital in March. Survey was carried out through a standardized questionnaire provided by Chinese Center for Disease Control and Prevention. Contents of the questionnaire would include: history of contact with SARS patient, route of infection, methods used for protection and so on. RESULTS (1) Distribution os SARS patients were confined to 3 wards: 4, 5, and 6 on the 7, 8, 12, 13 and 14 floors in the west unit of the inpatient building. Most of the inpatients were elderly and having severe original diseases. (2) Index patients were the first generation source of transmission and they infected inpatients and medical staff, making them the second generation. People with latent infection who had close contact with SARS patients might also serve as the possible source of transmission. (3) The major transmission routes were: near distant droplet infection and close contact infection. There was also a clue to the probability of aerosol or droplet nuclei infection through air-conditioning and ventilation system. CONCLUSION Nosocomial infection appeared to be the main characteristic of the SARS epidemic in the early stage of this hospital. Other than close contact and near space airborne transmission of SARS virus, the possibility of long-distance aerosol transmission called for further epidemiological and experimental studies in the future.


title: Four cases with Kawasaki disease and viral infection: aetiology or association.

text: The aetiology of Kawasaki disease has not yet been precisely determined. It has been associated with a variety of bacterial and viral agents. Some viruses including human adenovirus, coronavirus, and parainfluenza virus type 3 have been isolated from patients with Kawasaki disease. Clinical presentation of patients with human coronavirus and adenovirus infections mimics Kawasaki disease. In addition, these viruses may also be detected in Kawasaki disease as a coinfection. In this report, we present four Kawasaki disease patients infected with adenovirus, coronavirus OC43/HKU1 and parainfluenza virus type 3.


title: Results after laparoscopic left anterior transperitoneal submesocolic adrenalectomy for the treatment of pheochromocytoma.

text: AIM Minimally invasive adrenalectomy is the treatment of choice for benign adrenal lesions including pheocromocytoma (PHE) and in selected patients with malignant lesions. The aim of the present study is to evaluate the authors' results after laparoscopic left anterior transperitoneal submesocolic adrenalectomy (LLATSA) for unilateral PHE. MATERIAL OF STUDY This study is a retrospective analysis of prospectively collected data. From 1994 to 2018, 552 patients underwent laparoscopic adrenalectomy (LA). Of these, 34 patients (14 men, 20 women, mean age 52.8 years) underwent LLATSA for PHE. RESULTS Mean operative time was 93.1 ± 44.9 minutes. Conversion to open surgery occurred in two patients due to difficult identification of the anatomy. Intraoperative blood pressure and heart rate instability were observed in four cases, but with no need for conversion. Postoperative morbidity was nil. One American Society of Anesthesiologists (ASA) III patient died on postoperative day 4 from acute myocardial infarction. Mean postoperative hospital stay was 3.8 ± 1.8 days (range 2 - 8). DISCUSSION The main advantage of this approach is the early ligation of the main adrenal vein prior to any gland manipulation. This reduces the risk of catecholamines' spread and consequently the risk of hemodynamic instability. Intraperitoneal dissection is limited and there is no need to mobilize the colon or pancreas, with a lower risk of complications from organ manipulation. CONCLUSIONS LLATSA is feasible and safe for the treatment of PHE. A randomized trial design and a larger cohort of patients would be required to confirm these conclusions. KEY WORDS Adrenal tumors, Adrenal lesions, Laparoscopic adrenalectomy, Pheochromocytoma, Transperitoneal anterior approach, Laparoscopic left anterior transperitoneal submesocolic adrenalectomy (LLATSA).


title: Single-port plus an additional port robotic complete mesocolic excision and intracorporeal anastomosis using a robotic stapler for right-sided colon cancer.

text: The concept of complete mesocolic excision and central vascular ligation for colonic cancer has been recently introduced. The paper describes a technique of right-sided complete mesocolic excision and intracorporeal anastomosis by using a single-port robotic approach with an additional conventional robotic port. We performed a single-port plus an additional port robotic surgery using the Da Vinci Single-Site platform via the Pfannenstiel incision and the wristed robotic instruments via an additional robotic port in the left lower quadrant. The total operative and docking times were 280 and 25 minutes, respectively. The total number of lymph nodes harvested was 36 and the proximal and distal resection margins were 31 and 50 cm, respectively. Single-port plus an additional port robotic surgery for right-sided complete mesocolic excision and intracorporeal anastomosis appears to be feasible and safe. This system can overcome certain limitations of the previous robotic systems and conventional single-port laparoscopic surgery.


First confirmation of porcine colonic spirochaetosis caused by Brachyspira pilosicoli in Iberian pigs in Spain.


title: Influenza vaccination coverage among health-care personnel --- United States, 2010-11 influenza season.

text: The Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee recommend that all U.S. health-care personnel (HCP) be vaccinated annually against influenza. Nonetheless, influenza vaccination coverage among HCP in the United States has increased slowly over the past decade; during the 2009-10 influenza season, 61.9% of HCP received seasonal influenza vaccination. To update data with estimates from the 2010-11 influenza season, CDC conducted an Internet-based survey of 1,931 HCP who participated in three online survey panels. This report summarizes the results of that survey, which indicated that overall influenza vaccination coverage among HCP was 63.5% during the 2010--11 influenza season, similar to coverage for the 2009-10 season. Among HCP who reported working at a facility where vaccination was required by their employer, 98.1% were vaccinated. Among HCP without such an employer requirement but who were offered vaccination onsite, greater coverage was associated with a personal reminder from the employer to get vaccinated (69.9%), vaccination availability at no cost (67.9%), and vaccination availability for >1 day (68.8%). Influenza vaccination of HCP is needed to protect patients from HCP-transmitted disease. Maximizing influenza vaccination for all HCP is an important part of any comprehensive infection-control program.


title: Proteomics analysis of gastric epithelial AGS cells infected with Epstein-Barr virus.

text: Effects of the Epstein-Barr virus (EBV) on cellular protein expression are essential for viral pathogenesis. To characterize the cellular response to EBV infection, differential proteomes of gastric epithelial AGS cells were analyzed with two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization- time of flight (MALDI-TOF) and liquid chromatography electrospray/ionization ion trap (LC-ESI-IT) mass spectrometry identification. Mass spectrometry identified 9 altered cellular proteins, including 5 up-regulated and 4 down-regulated proteins after EBV infection. Notably 2-DE analysis revealed that EBV infection induced increased expression of heat shock cognate 71 kDa protein, actin cytoplasmic 1, pyridoxine-5'-phosphate oxidase, caspase 9, and t-complex protein 1 subunit alpha. In addition, EBV infection considerably suppressed those cellular proteins of zinc finger protein 2, cyclin-dependent kinase 2, macrophage-capping protein, and growth/ differentiation factor 11. Furthermore, the differential expressional levels of partial proteins (cyclin-dependent kinase 2 and caspase 9) were confirmed by Western blot analysis.Thus, this work effectively provided useful protein-related information to facilitate further investigation of the mechanisms underlying EBV infection and pathogenesis.


IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB), newsletter 1999.


title: Atmospheric movement of microorganisms in clouds of desert dust and implications for human health.

text: Billions of tons of desert dust move through the atmosphere each year. The primary source regions, which include the Sahara and Sahel regions of North Africa and the Gobi and Takla Makan regions of Asia, are capable of dispersing significant quantities of desert dust across the traditionally viewed oceanic barriers. While a considerable amount of research by scientists has addressed atmospheric pathways and aerosol chemistry, very few studies to determine the numbers and types of microorganisms transported within these desert dust clouds and the roles that they may play in human health have been conducted. This review is a summary of the current state of knowledge of desert dust microbiology and the health impact that desert dust and its microbial constituents may have in downwind environments both close to and far from their sources.


title: Substrate specificity of the human coronavirus 229E 3C-like proteinase.

text: Coronavirus gene expression involves proteolytic processing of the gene 1-encoded polyproteins and a key enzyme in this process is the virus-encoded 3C-like proteinase. In this study, we describe the biosynthesis of the human coronavirus 229E 3C-like proteinase in Escherichia coli and the substrate specificity of the purified protein. Using immunofluorescence microscopy, we have also investigated the subcellular localization of the 3C-like proteinase and have found a punctate, perinuclear distribution of the proteinase in virus-infected cells.


title: Identification of viral antigens that induce antibody responses on exposure to coronaviruses.

text: Various techniques were used to look for protective, non-cross-reactive antibodies in the sera of cats exposed to virulent feline infectious peritonitis virus (FIPV). Antibodies reactive with feline enteric coronavirus (FECV) from FIPV-exposed cats were adsorbed by several passages over an FECV-Sepharose column. In an ELISA against FECV and FIPV, the activity against both viruses was removed at the same rate; thus, no FIPV-specific antibodies could be identified. By gel electrophoresis-derived ELISA, the responses of cats surviving FIPV exposure were compared with those of cats succumbing to FIPV exposure to determine whether survival could be correlated with an antibody response against a particular virus protein. Results indicated that both groups responded in the same way to the matrix envelope protein and nucleocapsid proteins. Even though the response to peplomer in each group was weak, the survivor group responded better to this protein. Furthermore, the response of this group to the peplomer protein had the highest correlation with virus neutralization titer.


title: Diagnostic methods for detection of respiratory RNA viruses.

text: This article is a comprehensive description of diagnostic methods for detection of RNA respiratory viruses - respiratory syncytial virus RSV, influenza A and B viruses, parainfluenza 1, 2 and 3 viruses, coronaviruses and rhinoviruses--from cell culture to molecular biology methods. Both patients and medical personnel appear to be at risk of viral infection, specially during the winter season. Moreover, many health care units lack viral diagnostic facilities; therefore, it is essential for medical personnel to have an understanding of the etiology, mechanisms of transmission and of all disposable today diagnostic methods of RNA respiratory viruses. Patients at greatest risk of acquiring nosocomial viral respiratory disease are children, patients with immunodeficiency and patients treated in intensive care.


title: Pharmacists Welcome FDA's Opioids REMS: How Directly Will They Be Affected?

text: Pharmacists will need to become well versed in the FDA's REMS for opioids.


title: Genome instability in BVDV: an examination of the sequence and structural influences on RNA recombination.

text: The cytopathogenic biotype of the pestivirus, bovine viral diarrhea virus, is frequently a product of nonhomologous recombination in the region of the genome encoding the viral NS2-NS3 proteins. The possibility that sequences or structures in this region contributed to a hotspot for RNA recombination was examined. A PCR-based strategy was used to examine viral genomic RNA isolated from tissue samples of cattle persistently infected with the noncytopathogenic biotype of the virus. Analysis of two different regions of the viral genome revealed that recombination was not restricted to particular sequences. Alignment of the genomic sequences undergoing recombination and examination of the predicted secondary structures of the participating RNAs revealed that the dissociation of partial, newly synthesized negative strand RNAs from the positive strand template occurred at many different sites on the molecule. Similarly, it appeared that the reassociation of the RNA polymerase complex with a second positive strand template was frequently influenced by short regions of homology between the nascent RNA strand and open secondary structures in the template molecule.


title: Several rat cell lines share a common defect in their inability to internalize murine coronaviruses efficiently.

text: Infection of rat cells, Schwannoma RN2, hepatoma HTC or myoblast L6, with the murine coronavirus JHM strain results in a persistent infection characterized by the release of virus over an extended period of time with a limited cytopathology. Several stages of the viral replication cycle have been examined in these cells in comparison to those in mouse L2 cells, which are totally permissive to JHM infection. Although the rat cells bound as much virus as the mouse cells. Their ability to internalize it was 40-fold less efficient than the mouse cells. This lower internalization efficiency was not enhanced by pH shock of infected cells, but was by treatment with polyethylene glycol. In all cell types there appeared to be no major differences in the ability of the internalized virus to replicate the viral RNA as determined by slot-blot analysis with a radiolabelled viral cDNA. A similar genetic mechanism appears to be operative in the lines because somatic cell hybrids formed between these lines in various combinations were also deficient in the ability to internalize bound virus. Taken together these results imply that rat cell lines in general share a common deficiency in their inability to internalize murine coronaviruses efficiently. This low efficiency in viral internalization may explain in part the ability of these lines to sustain persistent infections.


title: Epidemiologic survey of bovine diseases in Suriname.

text: A seroepidemiologic survey of cattle diseases was undertaken in Suriname in 1985 to help assess the livestock disease situation in that country. The six diseases covered by the survey were bovine coronavirus infection, bovine rhinotracheitis, bovine virus diarrhea, brucellosis, parainfluenza-3 infection, and respiratory syncytial virus infection. The results indicated relatively low prevalences of these diseases compared to the prevalences found in most developed countries. The reasons for this are uncertain, but the finding suggests that the cattle population in Suriname could lack extensive exposure to these diseases and so could be highly susceptible to them. In addition, the evident need for more thoroughgoing survey data points up the need to establish a continuous animal data health monitoring system in Suriname--as well as in other developing countries where there is a need to objectively assess the livestock disease picture.


title: Pre-oligodendrocytes from adult human CNS.

text: CNS remyelination and functional recovery often occur after experimental demyelination in adult rodents. This has been attributed to the ability of mature oligodendrocytes and/or their precursor cells to divide and regenerate in response to signals in demyelinating lesions. To determine whether oligodendrocyte precursor cells exist in the adult human CNS, we have cultured white matter from patients undergoing partial temporal lobe resection for intractable epilepsy. These cultures contained a population of process-bearing cells that expressed antigens recognized by the O4 monoclonal antibody, but these cells did not express galactocerebroside (a marker for oligodendrocytes), glial fibrillary acidic protein (a marker for astrocytes), or vimentin. Selective elimination of O4-positive (O4+) cells by complement-mediated lysis resulted in inhibition of oligodendrocyte development in vitro. Since O4+ cells have an antigenic phenotype reminiscent of the rat adult oligodendrocyte-type 2 astrocyte progenitor and appear to develop into oligodendrocytes rather than type 2 astrocytes with time in culture, we call them "pre-oligodendrocytes." Neither pre-oligodendrocytes nor oligodendrocytes incorporated 3H-thymidine in response to rat astrocyte-conditioned medium, platelet-derived growth factor, insulin-like growth factor (IGF-1), or basic fibroblast growth factor (bFGF). However, IGF-1 increased the relative abundance of oligodendrocytes to pre-oligodendrocytes, while bFGF had the opposite effect. Cells with the antigenic phenotype of pre-oligodendrocytes were also identified in tissue prints of adult human white matter. We propose that, in human demyelinating diseases such as multiple sclerosis, pre-oligodendrocytes may divide and/or migrate in response to signals present in demyelinated lesions and thus facilitate remyelination.


title: Expression of viral proteins in feline leukemia virus-associated enteritis.

text: Fourteen cases of feline leukemia virus (FeLV)-associated enteritis were immunohistologically examined for the expression of FeLV proteins gp70, p27, and p15E in the jejunum, mesenteric lymph nodes, spleen, and bone marrow. Results were compared with those of FeLV-infected cats without intestinal alterations. Other viral infections and specific bacterial, fungal, and parasitic infections were excluded by standard microbiologic methods, histopathology, immunohistology, and in situ hybridization. In FeLV-associated enteritis, FeLV gp70 and p15E were strongly expressed in intestinal crypt epithelial cells. In contrast, FeLV-positive cats without intestinal alterations showed only faint staining for gp70 and p15E and comparatively strong p27 expression in these cells. Findings suggest a direct relation between FeLV infection and alterations in intestinal crypt epithelial cells that may be attributed to the envelope proteins gp70 and p15E and/or their precursor protein. Distinct similarities to the intestinal changes in the experimentally induced FeLV-feline AIDS syndrome are obvious, suggesting that naturally occurring feline AIDS variants may be responsible for FeLV-associated enteritis.


Toroviruses--members of the coronavirus superfamily?


title: Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors.

text: OBJECTIVE To examine the impact of severe acute respiratory syndrome (SARS) on pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among survivors. METHODS 110 survivors with confirmed SARS were evaluated at the Prince of Wales Hospital, HK at the end of 3 and 6 months after symptom onset. The assessment included lung volumes (TLC, VC, RV, FRC), spirometry (FVC, FEV1), carbon monoxide transfer factor (TLCO adjusted for haemoglobin), inspiratory and expiratory respiratory muscle strength (Pimax and Pemax), 6 minute walk distance (6MWD), chest radiographs, and HRQoL by SF-36 questionnaire. RESULTS There were 44 men and 66 women with a mean (SD) age of 35.6 (9.8) years and body mass index of 23.1 (4.8) kg/m2. Seventy (64%) were healthcare workers. At 6 months 33 subjects (30%) had abnormal chest radiographs; four (3.6%), eight (7.4%), and 17 (15.5%) patients had FVC, TLC, and TLCO below 80% of predicted values; and 15 (13.9%) and 24 (22.2%) had Pimax and Pemax values below 80 cm H2O, respectively. The 6MWD increased from a mean (SD) of 464 (83) m at 3 months to 502 (95) m (95% CI 22 to 54 m, p<0.001), but the results were lower than normal controls in the same age groups. There was impairment of HRQoL at 6 months. Patients who required ICU admission (n = 31) had significantly lower FVC, TLC, and TLCO than those who did not. CONCLUSION The exercise capacity and health status of SARS survivors was considerably lower than that of a normal population at 6 months. Significant impairment in surface area for gas exchange was noted in 15.5% of survivors. The functional disability appears out of proportion to the degree of lung function impairment and may be related to additional factors such as muscle deconditioning and steroid myopathy.


title: Barriers and facilitators to establishing a national public health observatory.

text: OBJECTIVE To determine what stakeholders perceive as barriers and facilitators to creating a national public health observatory (PHO) in Trinidad and Tobago. METHODS A descriptive study was conducted based on 15 key informant interviews carried out from April to September 2013. The key informants worked within the health care sector in Trinidad and Tobago. Using a semi-structured interview guide, information was collected on knowledge, attitudes, and beliefs about creating a PHO; barriers and facilitators to creating and sustaining a PHO; legal considerations; and human resource and information technology requirements. Common themes of the responses were identified. RESULTS The majority of participants supported the development of a national PHO, recognized its value in informing their work, and indicated that a national PHO could 1) provide information to support evidence-informed decision-making for health policy and strategic planning; 2) facilitate data management by establishing data policies, procedures, and standards; 3) increase the use of data by synthesizing and disseminating information; and 4) provide data for benchmarking. However, a number of barriers were identified, including 1) the perception that data collection is not valued; 2) untimely availability of data; 3) limited data synthesis, dissemination, and utilization to inform decision-making; and 4) challenges related to the allocation of human resources and existing information technology. CONCLUSIONS Key informants support the development of a national PHO in Trinidad and Tobago. The findings align well within the components of the conceptual framework for establishing national health observatories. A stepwise approach to establishing a national PHO in Trinidad and Tobago, beginning with structural components and followed by functional components, is recommended. A national PHO in Trinidad and Tobago could serve as a model for other countries in the Caribbean.