title: Development and validation of a high-throughput screen for inhibitors of SARS CoV and its application in screening of a 100,000-compound library.

text: The authors have developed a high-throughput screen (HTS) that allows for the identification of potential inhibitors of the severe acute respiratory syndrome coronavirus (SARS CoV) from large compound libraries. The luminescent-based assay measures the inhibition of SARS CoV-induced cytopathic effect (CPE) in Vero E6 cells. The assay was validated in 96-well plates in a BSL3 containment facility. The assay is sensitive and robust, with Z values > 0.6, signal to background (S/B) > 16, and signal to noise (S/N) > 3. The assay was further validated with 2 different diversity sets of compounds against the SARS CoV. The "hit" rate for both libraries was approximately 0.01%. The validated HTS assay was then employed to screen a 100,000-compound library against SARS CoV. The hit rate for the library in a single-dose format was determined to be approximately 0.8%. Screening of the 3 libraries resulted in the identification of several novel compounds that effectively inhibited the CPE of SARS CoV in vitro-compounds which will serve as excellent lead candidates for further evaluation. At a 10-microM concentration, 3 compounds with selective indexes (SI50) of > 53 were discovered.


title: Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors.

text: Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.


Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Executive summary. Sinus and Allergy Health Partnership.


title: Replication and packaging of transmissible gastroenteritis coronavirus-derived synthetic minigenomes.

text: The sequences involved in the replication and packaging of transmissible gastroenteritis virus (TGEV) RNA have been studied. The structure of a TGEV defective interfering RNA of 9.7 kb (DI-C) was described previously (A. Mendez, C. Smerdou, A. Izeta, F. Gebauer, and L. Enjuanes, Virology 217: 495-507, 1996), and a cDNA with the information to encode DI-C RNA was cloned under the control of the T7 promoter. The molecularly cloned DI-C RNA was replicated in trans upon transfection of helper virus-infected cells and inhibited 20-fold the replication of the parental genome. A collection of 14 DI-C RNA deletion mutants (TGEV minigenomes) was synthetically generated and tested for their ability to be replicated and packaged. The smallest minigenome (M33) that was replicated by the helper virus and efficiently packaged was 3.3 kb. A minigenome of 2.1 kb (M21) was also replicated, but it was packaged with much lower efficiency than the M33 minigenome, suggesting that it had lost either the sequences containing the main packaging signal or the required secondary structure in the packaging signal due to alteration of the flanking sequences. The low packaging efficiency of the M21 minigenome was not due to minimum size restrictions. The sequences essential for minigenome replication by the helper virus were reduced to 1,348 nt and 492 nt at the 5' and 3' ends, respectively. The TGEV-derived RNA minigenomes were successfully expressed following a two-step amplification system that couples pol II-driven transcription in the nucleus to replication supported by helper virus in the cytoplasm, without any obvious splicing. This system and the use of the reporter gene beta-glucuronidase (GUS) allowed minigenome detection at passage zero, making it possible to distinguish replication efficiency from packaging capability. The synthetic minigenomes have been used to design a helper-dependent expression system that produces around 1.0 microgram/10(6) cells of GUS.


Tobacco control in Australia: victims of our past success?


title: Extremely Low Frequency Electromagnetic Field from Convective Air Warming System on Temperature Selection and Distance.

text: BACKGROUND Hypothermia generates potentially severe complications in operating or recovery room. Forced air warmer is effective to maintain body temperature. Extremely low frequency electromagnetic field (ELF-EMF) is harmful to human body and mainly produced by electronic equipment including convective air warming system. We investigated ELF-EMF from convective air warming device on various temperature selection and distance for guideline to protect medical personnel and patients. METHODS The intensity of ELF-EMF was measured as two-second interval for five minutes on various distance (0.1, 0.2, 0.3, 0.5 and 1meter) and temperature selection (high, medium, low and ambient). All of electrical devices were off including lamp, computer and air conditioner. Groups were compared using one-way ANOVA. P<0.05 was considered significant. RESULTS Mean values of ELF-EMF on the distance of 30 cm were 18.63, 18.44, 18.23 and 17.92 milligauss (mG) respectively (high, medium, low and ambient temperature set). ELF-EMF of high temperature set was higher than data of medium, low and ambient set in all the distances. CONCLUSION ELF-EMF from convective air warming system is higher in condition of more close location and higher temperature. ELF-EMF within thirty centimeters exceeds 2mG recommended by Swedish TCO guideline.


title: [Comparison between two different mesh fixation methods in laparoscopic inguinal hernia repair: tacker vs. Synthetic cyanoacrylate glue.]

text: AIM The aim of this retrospective study was to compare the results of two different mesh fixation methods in laparoscopic transabdominal preperitoneal hernioplasty (TAPP): tacker vs. synthetic cyanoacrylate glue. METHODS The study group includes 70 patients with bilateral and monolateral recurrent inguinal hernia undergoing transabdominal preperitoneal repair (TAPP) in the period 2011-2013. A polypropylene mesh was fixed in group A (N.=35) with titanium tacks (EndoUniversal stapler, Covidien) or in group B (N.=35) with synthetic cyanoacrylate glue (Glubran-2, GEM). Patient outcome was assessed by the following variables: sex, mean age, ASA score, intra- and postoperative morbidity, hospitalization, postoperative acute and chronic pain, recurrence rate. The observation period was 24 months, with a mean follow-up of 10.5 months (range, 1-23) for Group A and 11 months (range, 2-24) for Group B. RESULTS No difference between the two groups was observed with respect to mean operative time and hospitalization. In all cases, surgery was successfully concluded laparoscopically. Intraoperative complications occurred in 1 patient of the group A and consisted of a urinary bladder injury, which was immediately sutured. Postoperative complication rate was 5.7% (4 patients, of whom 3 in group A and 1 in group B). In each group we detected one recurrence within 6 (group A) and 18 months (group B) postsurgery; both patients were treated with a re-TAPP. Postoperative pain at 6 months from surgery, measured by visual analogue score (VAS), was reported by 4 patients in the group A and in no case of the group B (P=0.04). CONCLUSION Data from this study demonstrate the advantages of synthetic cyanoacrylate glue for mesh fixation in laparoscopic transabdominal preperitoneal inguinal hernia repair, compared to titanium tacks. The use of this surgical glue was associated with a significantly reduced risk for developing chronic groin pain and a shortened hospital stay. Nevertheless, further studies with longer follow-up periods are needed to confirm our encouraging results.


title: The pathogenesis of turkey origin reoviruses in turkeys and chickens.

text: Avian reoviruses that have been shown to be genetically distinct from chicken origin reoviruses were isolated from commercial turkey flocks in the Southeastern US and Texas that were experiencing enteritis. The pathogenesis of these turkey origin reoviruses (TRVs) was evaluated in commercial and specific pathogen free (SPF) turkey poults and SPF chickens. Mortality, clinical disease, gross lesions, microscopic lesions and body weights were observed. TRVs replicated poorly and did not cause disease in chickens. Clinical disease induced by the TRV isolates, characterized by diarrhoea and depression, was mild in both SPF and commercial origin poults. Several TRV isolates caused moderate to severe bursal atrophy in poults. Additionally, each of the TRV isolates caused significant body weight decreases in SPF and/or commercial poults as compared with sham inoculates. Molecular characterization of the isolates revealed that the TRVs and chicken origin reoviruses had identical electropherotype profiles.


title: Megatrends in Infectious Diseases: The Next 10 to 15 Years.

text: It has been about 100 years since the Spanish influenza pandemic of 1918-19 that killed an estimated 50 million individuals globally. While we have made remarkable progress in reducing infection-related mortality, infections still account for 13 to 15 million deaths annually. This estimate is projected to remain unchanged until 2050. We have identified 4 megatrends in infectious diseases and these are "emerging and re-emerging infections", "antimicrobial resistance", "demographic changes" and "technological advances". Understanding these trends and challenges should lead to opportunites for the medical community to reshape the future. Further inroads will also require broad approaches involving surveillance, public health and translating scientific discoveries into disease control efforts.


title: Differential detection of transmissible gastroenteritis virus and porcine epidemic diarrhea virus by duplex RT-PCR.

text: Transmissible gastroenteritis (TGE) and porcine epidemic diarrhea (PED) are highly contagious enteric diseases of piglets. The clinical signs of these diseases are very similar and include watery, yellowish diarrhea. Thus, the effective differential detection of TGE virus and PED virus is required. In the present study, a duplex reverse transcription-polymerase chain reaction (RT-PCR) was established for the differential detection of TGE and PED viruses. The primers were designed for the S gene of each virus. RNA was extracted from the intestines and stool samples that were collected from the swine with diarrhea. The RT-PCR test could detect both TGE and PED viruses with 2 TCID50/200 microl. Among 90 clinical samples, 7 TGE viruses and 2 PED viruses were detected by the duplex RT-PCR. This duplex RT-PCR may be a useful diagnostic method for the rapid, specific, and sensitive differential detection of TGE and PED viruses using clinical samples.


Lack of training in biodefense research leading to dangerous leaks.


title: Radiofrequency ablation of phalangeal osteoid osteoma: technical challenges encountered in small bones.

text: Osteoid osteoma, a benign bone tumor, is characterized by a generally less than 1 cm nidus surrounded by a zone of reactive sclerosis. It is frequently located in the femur and tibia; on the other hand in up to 5% of cases it may be presented in upper extremities. In previous years, its treatment was usually open surgery with en-bloc resection or curettage of the tumor. Various minimal invasive percutaneous treatments including radiofrequency ablation became popular in last years. In this report, the difficulties encountered during radiofrequency ablation treatment in small bones is described in a 19-year-old female case of osteoid osteoma.


title: Lack of correlation between nutritional status and seroprotection against influenza in a long term care facility.

text: UNLABELLED We conducted a prospective study in a long-term care facility. Virologic diagnosis was assessed using viral isolation, polymerase chain reaction and serology for all patients with a flu-like syndrome. Albumin, vitamins and trace elements were also measured. RESULTS The risk of influenza increased 6.5-fold in patients with an antibody titer of 40 during the influenza outbreak (P=0.04). Micronutrients and vitamins deficiencies were important. Patients with antibody titer >1:40 could still be infected by the virus without correlation with the nutritional status. CONCLUSION Humoral protection with a titer >1:40 might not be protective in the elderly. Nutritional deficiencies were too prevalent to detect any effect on the results.


title: [Covert infection of severe acute respiratory syndrome in health-care professionals and its relation to the workload and the type of work].

text: OBJECTIVE To study severe acute respiratory syndrome (SARS) covert infection in health-care professionals and its relation to work intensity and type of work. METHODS Specific antibodies to SARS virus in 1 127 serum specimens from health-care professionals who had a close contact history with patients of SARS and 92 healthy persons were assayed with ELISA. RESULTS The health-care professionals consisted of 287 men and 840 women, aged 21 - 55 years (mean 34 +/- 9 years). The overall positive rate of specific IgG and IgM was 2.57% (29/1 127); the positive rates in nurses, doctors and laboratory workers, and supervisors were 3.46%, 1.41%, 2.86%, respectively. 34.5% of the infected worked in the ICU, and 65.5% in the general wards. None of them presented clinical SARS. Medical examination was also carried out for 313 people who had close contact with the 29 antibody positive health care professionals, but no clinical SARS was found. CONCLUSIONS Covert infection can be found in the health-care professionals and it showed no contagiousness. The positive rate of specific antibodies was higher in ICU where the work intensity was higher. The positive rate in nurses was higher than in doctors.


title: The experience of the 2003 SARS outbreak as a traumatic stress among frontline healthcare workers in Toronto: lessons learned.

text: The outbreak of severe acute respiratory syndrome (SARS) in the first half of 2003 in Canada was unprecedented in several respects. Understanding the psychological impact of the outbreak on healthcare workers, especially those in hospitals, is important in planning for future outbreaks of emerging infectious diseases. This review draws upon qualitative and quantitative studies of the SARS outbreak in Toronto to outline the factors that contributed to healthcare workers' experiencing the outbreak as a psychological trauma. Overall, it is estimated that a high degree of distress was experienced by 29-35% of hospital workers. Three categories of contributory factors were identified. Relevant contextual factors were being a nurse, having contact with SARS patients and having children. Contributing attitudinal factors and processes were experiencing job stress, perceiving stigmatization, coping by avoiding crowds and colleagues, and feeling scrutinized. Pre-existing trait factors also contributed to vulnerability. Lessons learned from the outbreak include: (i) that effort is required to mitigate the psychological impact of infection control procedures, especially the interpersonal isolation that these procedures promote; (ii) that effective risk communication is a priority early in an outbreak; (iii) that healthcare workers may have a role in influencing patterns of media coverage that increase or decrease morale; (iv) that healthcare workers benefit from resources that facilitate reflection on the effects of extraordinary stressors; and (v) that healthcare workers benefit from practical interventions that demonstrate tangible support from institutions.


Severe acute respiratory syndrome.


title: Live, attenuated coronavirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis.

text: Feline infectious peritonitis (FIP) is a fatal immunity-mediated disease caused by mutants of a ubiquitous coronavirus. Since previous attempts to protect cats under laboratory and field conditions have been largely unsuccessful, we used our recently developed system of reverse genetics (B. J. Haijema, H. Volders, and P. J. M. Rottier, J. Virol. 77:4528-4538, 2003) for the development of a modified live FIP vaccine. With this objective, we deleted the group-specific gene cluster open reading frame 3abc or 7ab and obtained deletion mutant viruses that not only multiplied well in cell culture but also showed an attenuated phenotype in the cat. At doses at which the wild-type virus would be fatal, the mutants with gene deletions did not cause any clinical symptoms. They still induced an immune response, however, as judged from the high levels of virus-neutralizing antibodies. The FIP virus (FIPV) mutant lacking the 3abc cluster and, to a lesser extent, the mutant missing the 7ab cluster, protected cats against a lethal homologous challenge; no protection was obtained with the mutant devoid of both gene clusters. Our studies show that the deletion of group-specific genes from the coronavirus genome results in live attenuated candidate vaccines against FIPV. More generally, our approach may allow the development of vaccines against infections with other pathogenic coronaviruses, including that causing severe acute respiratory syndrome in humans.


title: Influenza A (H1N1) virus resistance to cyanovirin-N arises naturally during adaptation to mice and by passage in cell culture in the presence of the inhibitor.

text: Influenza A/New Caledonia/20/99 (H1N1) virus was studied for development of resistance to cyanovirin-N (CVN). CVN neutralizes virus infectivity by binding to specific high-mannose oligosaccharides on the viral haemagglutinin 1 (HA1) subunit. During virus adaptation to mice in the absence of CVN treatment the virus became resistant to CVN (CVN-MR virus), as did virus passaged in cell culture in the presence of CVN (CVN-R virus). The CVN-R virus possessed a single amino acid change at position 94a (Asn94aAsp) of HA1 that eliminated this glycosylation site. The CVN-MR virus at mouse passage 7 was a mixture of clones, consisting of a single mutation (Asp225Gly) and double mutations (Asn63Ser+Asp225Gly or Asn94a+Asp225Gly), eliminating glycosylation sites. CVN did not bind well to the CVN-R and CVN-MR viruses. Propagating these viruses in cells treated with 1 mM deoxymannojirimycin (dMJ, mannosidase inhibitor) increased sensitivity to CVN, suggesting that glycans attached at other sites on HA1 that typically are not high-mannosidic became so due to dMJ treatment. Further evaluation showed that the Asp225Gly mutant virus was sensitive to the inhibitor and did not kill mice or induce weight loss. The CVN-R virus was also avirulent to mice. The double-mutant CVN-MR viruses were resistant to CVN and caused deaths and severe weight loss in mice. CVN-R virus subjected to mouse adaptation acquired the 225 mutation and a lethal phenotype. Thus, the 225 mutation in the HA receptor-binding site in combination with a loss of glycan at Asn (63 or 94a) are important for mouse adaptation in this virus. The mutations reported here causing resistance to CVN are consistent with its known mode of action.


An outbreak of acute respiratory infections due to human respiratory syncytial virus in a nursing home for the elderly in Ibaraki, Japan, 2014.


title: New simulation-based airway management training program for junior physicians: Advanced Airway Life Support.

text: BACKGROUND All junior physicians in Taiwan were enrolled into a 3-month post-graduate year 1 (PGY1) course after Severe Acute Respiratory Syndrome (SARS) attack in 2003. AIMS To develop and evaluate a new airway management training protocol by using an integrated course of lectures, technical workshops and medical simulations. METHODS In each PGY1 course, the trainees participated in the Advanced Airway Life Support (AALS) program. After 2 h lecture, the trainees were divided into three groups for 4 h technical workshop, including 10 skill stations and medical simulation at the Clinical Skills Resources Center of the hospital at different times. Video-based debriefing and feedback were performed after each simulation. The same scenario was re-simulated after debriefing. Participants' performance was assessed by single global rating and a 5 key actions scoring. RESULTS A total of 266 junior physicians have been trained with this AALS programs in 2 years. They learned the techniques of airway management, passed the performance checklist of technical workshop, and received higher scores during re-simulation regardless of scoring methods. CONCLUSIONS The AALS training program can provide methodical and systematic training for junior residents to mature with specialized technical skills and higher-order cognitive skills, behaviors and leadership in airway management.


title: Challenges faced by hospital healthcare workers in using a syndrome-based surveillance system during the 2003 outbreak of severe acute respiratory syndrome in Taiwan.

text: Because the severe acute respiratory syndrome (SARS) outbreak in Taiwan in 2003 was worsened by hospital infections, we analyzed 229 questionnaires (84.8% of 270 sent) completed by surveyed healthcare workers who cared for patients with SARS in 3 types of hospitals, to identify surveillance problems. Atypical clinical presentation was the most often reported problem, regardless of hospital type, which strongly indicates that more timely syndromic surveillance was needed.


title: [Effectiveness of the implementation of clinical-epidemiological management during Covid-19 in a medium-long-stay hospital.]

text: OBJECTIVE The effects of the Covid-19 health emergency have demonstrated the high vulnerability of people residing in medium and long-stay centers, with high mortality rates. Little data is available about contingency protocols to minimize the spread of the virus in these centers. The goal of this study was to describe the clinical and epidemiological features of patients affected by SARS-CoV-2 and the preventive and management measures adopted at the National Hospital for Paraplegics (Toledo, Castilla-La Mancha, Spain) to minimize the risk of transmission of Covid-19. METHODS A team of specialists in Preventive and Internal Medicine established a protocol for active surveillance, identification of suspected and confirmed cases, and follow-up of contacts. Also, a Unit for the care of confirmed cases was created with personnel specifically trained in Covid-19, to achieve better patient care and optimize the available resources. Descriptive statistical measures have been used to analyze the data. RESULTS The prevalence of Covid-19 was 12.2%, with a cumulative incidence of 8.2%. After the protocol was established, control of the disease was achieved without hospital transmission after its application. Due to the alarm generated at the start of the pandemic, up to 45% of the requested RT-PCRs did not meet the criteria of the Ministry of Health, all of which were negative. The clinical characteristics of our patients differed slightly from those observed in other studies published in the general population, with cough and asthenia being the most frequent symptoms, present in 69.2% and 38.5%, respectively. 100% of the infected patients did not present complications that required assistance in the Intensive Care Unit. CONCLUSIONS With the application of preventive and organizational actions, we consider that we have presented a low incidence of those infected. The preparation of protocols and their supervision is essential for the rapid identification of cases and optimization of the tests requested. Despite being a medium and long-stay hospital, we have not presented any mortality or complications that required admission to the Intensive Care Unit.


title: [Clinical pathology and pathogenesis of severe acute respiratory syndrome].

text: BACKGROUND To explore the pathological features and pathogenesis of severe acute respiratory syndrome (SARS) to provide evidence for the clinical treatment and prevention of SARS. METHODS Pathological features of 2 cases of full autopsy and 4 cases of needle biopsy tissue samples from the patients who died from SARS were studied by light and electron microscopy. The distribution and quantity of lymphocyte subpopulations in the lungs and immune organs from SARS patients were analyzed by immunohistochemistry. The location and semi-quantitative analysis of SARS coronavirus in the tissue specimens were studied by electron microscopy, in situ hybridization and immunohistochemistry. RESULTS In total of 6 cases, diffuse alveolar damage and alveolar cell proliferation were common. The major pathological changes of 2 autopsy cases of SARS in lung tissues were acute pulmonary interstitial and alveolar exudative inflammation, and 2 autopsy and one biopsy lung tissues showed alveolar hyaline membrane formation. Terminal bronchiolar and alveolar desquamation of lung tissues in one autopsy and 2 biopsy cases were noted. Among 6 cases, 2 biopsy cases presented early pulmonary fibrosis and alveolar organization. Meanwhile, the immune organs, including lymph nodes and spleens from 2 autopsy cases of SARS whose disease courses were less than 12 days showed extensive hemorrhagic necrosis, reactive macrophage/histocyte proliferation, with relative depression of mononuclear and granulocytic clones in the bone marrows. However, spleen and bone marrow biopsy tissue samples from 4 dead SARS cases whose clinical course lasted from 21 to 40 days presented repairing changes. SARS coronaviruses were mainly identified in type I and II alveolar epithelia, macrophages, and endothelia; meanwhile, some renal tubular epithelial cells, cardiomyocytes, mucosal and crypt epithelial cells of gastrointestinal tracts, parenchymal cells in adrenal glands, lymphocytes, testicular epithelial cells and Leydig's cells were also detected by electron microscopy combined with in situ hybridization. The semi-quantitative analysis of lymphocyte subpopulations revealed that the proportion of CD8+ T lymphocytes were about 80% of the total infiltrative inflammatory cells in the pulmonary interstitium, with a few CD4+ lymphocytes CD3+, CD4+, CD8+ or CD20+ lymphocyte subpopulations were obviously decreased and there was imbalance in number and proportion, while CD57+, CD68+, S-100+ and HLA-DR+ cells were relatively increased in lymph nodes and spleens. CONCLUSIONS Histologically, the pulmonary changes could be divided into acute inflammatory exudative, terminal bronchiolar and alveolar desquamative and proliferative repair stages or types during the pathological process of SARS. SARS coronavirus was found in multi-target cells in vivo, which means that SARS coronavirus might cause multi-organ damages which were predominant in lungs. There were varying degrees of decrease and imbalance in number and proportion of lymphocyte subpopulations in the immune organs of the patients with SARS. However, these changes may be reversible. It was found that cellular immune responses were predominant in the lungs of SARS cases, which might play an important role in getting rid of coronaviruses in infected cells and inducing immune mediated injury.


Some recent developments in virology.


title: [A Case of Aortitis Caused by a Granulocyte-Colony-Stimulating Factor during Chemotherapy for Pancreatic Cancer].

text: BACKGROUND Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor(G-CSF), has been used as prophylaxis for severe hematotoxicity induced by chemotherapy. We report a case of aortitis induced by pegfilgrastim administration during modified FOLFIRINOX(mFOLFIRINOX)chemotherapy for metastatic pancreatic cancer. CASE REPORT A 65-year-old woman underwent a distal pancreatectomy for pancreatic tail cancer. Liver metastases appeared 2 years after the surgery. mFOLFIRINOX chemotherapy was started with prophylactic administration of pegfilgrastim. Eight days after the first administration and 6 days after administration of the 8th course, the patient developed a fever. The blood test results indicated severe inflammation. Computed tomography revealed a thickened aorta indicating aortitis. The symptoms rapidly improved with antibiotic therapy. We diagnosed aortitis induced by pegfilgrastim administration. CONCLUSION Aortitis should be considered when a patient has unidentified inflammatory findings after receiving pegfilgrastim.


title: [Coronaviruses].

text: Coronaviruses contain positive-stranded RNA with ca. 30 kb as a genome, which is wrapped by the envelope, and constitute Nidovirales together with Arteriviridae. The feature of viruses in Nidovirales is the unique structure of the mRNA set, called 3' co-terminal nested set. Coronaviruses have several to more than 10 different species of subgenomic mRNA and generally only the OFR located in the 5' end of each mRNA is translated. The 5' 20 kb of the coronavirus genome or mRNA-1 consists of two ORFs, 1a and 1b, between that there is a unique RNA structure called pseudoknot. From mRNA-1, 1a as well as 1a+1b are translated; the latter 1a+1b results from the translation due to ribosomal frame-shifting facilitated by the pseudoknot structure. From those two proteins, totally 16 proteins are produced as a result of auto-cleavage by the proteases included in la protein. Those proteins exhibit different functions, such as RNA-dependent RNA polymerase, helicase, proteases and proteins that regulate cellular functions, mRNAs smaller than mRNA-2 translate in general the structural proteins, nucleocapsid (N) protein, spike (S) protein, integrated membrane (M) protein and envelope (E) proteins. Those proteins assemble to the vesicles located from ER to Golgi (ER Golgi intermediate compartment) and virions bud into the vesicles. Those virions are released from infected cells via exocytosis.


title: [Coronaviruses].

text: Corona viruses belong to a group of not yet well known viruses isolated in patients with infections of the upper respiratory organs, especially in winter months. It is presumed that they provoke about 15% - 20% of all infections. However, in the last years more attention has been paid to the role of human corona viruses in the provocation of sickness in man and they are becoming a special field of interest in scientific studies.


title: Transmission of severe acute respiratory syndrome in dynamical small-world networks.

text: The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.


title: Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women.

text: The high incidence of lung cancer among Chinese females, despite a low smoking prevalence, remains poorly explained. Cooking fume exposure during frying could be an important risk factor. We carried out a population-based case-control study in Hong Kong. Cases were Chinese female nonsmokers with newly diagnosed primary lung cancer. Controls were female nonsmokers randomly sampled from the community, frequency matched by age groups. Face-to-face interviews were conducted using a standardized questionnaire. The "total cooking dish-years," categorized by increments of 50, was used as a surrogate of cooking fumes exposure. Multiple unconditional logistic regression was used to estimate the odds ratios (OR) for different levels of exposure after adjusting for various potential confounding factors. We interviewed 200 cases and 285 controls. The ORs of lung cancer across increasing levels of cooking dish-years were 1, 1.17, 1.92, 2.26, and 6.15. After adjusting for age and other potential confounding factors, the increasing trend of ORs with increasing exposure categories became clearer, being 1, 1.31, 4.12, 4.68, and 34. The OR of lung cancer was highest for deep-frying (2.56 per 10 dish-years) followed by that of frying (1.47), and stir-frying had the lowest OR (1.12) among the three methods. Cumulative exposure to cooking by means of any form of frying could increase the risk of lung cancer in Hong Kong nonsmoking women. Practical means to reduce exposures to cooking fumes should be given top priority in future research.


title: [Research advances in cardiovascular system damage caused by SARS-CoV-2 in children].

text: The outbreak of coronavirus disease 2019 (COVID-19) started in December 2019 in China and the epidemic is still going on at present. Since children are the susceptible population, the number of cases is gradually increasing. In addition to the typical respiratory symptoms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection also has the clinical symptoms of cardiovascular system damage. Based on a literature review, this article discusses the possible cardiovascular system damage caused by SARS-CoV-2 in children and related mechanisms, in order to provide help for the timely treatment and prevention of cardiovascular system damage caused by SARS-CoV-2 in children.


title: Detection of human metapneumovirus RNA sequences in nasopharyngeal aspirates of young French children with acute bronchiolitis by real-time reverse transcriptase PCR and phylogenetic analysis.

text: Human metapneumovirus (HMPV) was the unique viral pathogen detected by a real-time reverse transcriptase PCR (RT-PCR) assay in 6 (6.4%) of 94 consecutive French children hospitalized for acute bronchiolitis from September 2001 to June 2002. This virus was identified as the third etiological cause of bronchiolitis, after respiratory syncytial virus and rhinovirus (35 [37%] and 21 [22%] of 94 cases, respectively). Phylogenetic analysis of F-gene sequences demonstrated the cocirculation of distinct HMPV genotypes during this study. These findings highlight the need to implement a rapid HMPV RT-PCR detection assay for the clinical diagnosis of respiratory infections in pediatric patients with bronchiolitis.


title: First report of Schistosoma mekongi infection with brain involvement.

text: We describe, to our knowledge, the first reported case of Schistosoma mekongi infection with brain involvement. S. mekongi is a distinct species most closely related to Schistosoma japonicum that is endemic in a defined area of the Mekong River in Laos and Cambodia and characteristically associated with hepatosplenic disease. The patient had an excellent response to praziquantel therapy but required repeated courses of corticosteroid therapy to suppress recrudescent neurological symptoms.


title: Immunogenicity and antigenicity of human coronaviruses 229E and OC43.

text: The immunogenicity and antigenicity of human coronaviruses 229E and OC43 were studied by quantitative immunoelectrophoresis. Three distinct antigens were recognized in both coronavirus strains when T-100-solubilized whole virus was tested by two-dimensional immunoelectrophoresis against homologous rabbit antiserum. No antigens cross-reacted between strains, but the electrophoretic patterns against homologous antiserum were highly similar in that both strains had one electrophoretically fast antigen, one of intermediate mobility, and one of slow mobility. Immunization of rabbits with 10(9) plaque-forming units of virus was required for production of antiserum which recognized the three antigens; lesser amounts gave rise to antisera which recognized only one or two components. Precipitin lines excised from two-dimensional immunoelectropherograms were used successfully as immunogens to prepare monospecific antiserum to each of the antigens of OC43 and 229E. Monospecific antiserum to the slow component of 229E neutralized 229E only, and monospecific antiserum to the slow component of OC43 both neutralized and inhibited hemagglutination of OC43 virus. Human convalescent sera which possessed both complement-fixing and neutralizing antibody also recognized the slow-moving component.


The surgeon as a risk factor.


title: The potential of antibody-mediated immunity in the defence against biological weapons.

text: Antibody-mediated immunity (AMI) has been used for the treatment and prevention of infectious diseases for > 100 years, and has a remarkable record of safety, efficacy and versatility. AMI can be used for defence against a wide variety of biological weapons, and passive antibody (Ab) therapy has the potential to provide immediate immunity to susceptible individuals. Recent advances in the Ab field make it possible to generate Abs with enhanced antimicrobial functions. There are significant gaps in our understanding of Ab function, such that the development of Ab-based strategies remains a largely empirical exercise. Nevertheless, the advantages inherent in the therapeutic and prophylactic use of AMI provide a powerful rationale for continued development that will undoubtedly yield many new vaccines and therapeutic Abs.


title: Noninvasive ventilation after early extubation in patients recovering from hypoxemic acute respiratory failure: a single-centre feasibility study.

text: PURPOSE The use of noninvasive ventilation (NIV) to facilitate discontinuation of mechanical ventilation in patients with acute hypoxemic respiratory failure (hypoxemic ARF) has never been explored. This pilot study aims to assess the feasibility of early extubation followed by immediate NIV, compared conventional weaning, in patients with resolving hypoxemic ARF. METHODS Twenty consecutive hypoxemic patients were randomly assigned to receive either conventional weaning or NIV. The changes in arterial blood gases and respiratory rate were compared between the two groups at 1, 12, 24 and 48 h. Differences in the rate of extubation failure, ICU and hospital mortality, number of invasive-ventilation-free-days at day 28, septic complications, number of tracheotomies, days and rates of continuous intravenous sedation, and ICU length of stay were also determined. RESULTS No patient interrupted the study protocol. Arterial blood gases were similar during invasive mechanical ventilation, 1 h after NIV application following extubation, and after 12, 24 and 48 h. Respiratory rate was higher after 1 h in the NIV group, but no different after 12, 24 and 48 h. The number of invasive-ventilation-free-days at day 28 was 20 ± 8 (min = 0, max = 25) days in the treatment group and 10 ± 9 (min = 0, max = 25) days in the control group (p = 0.014). The rate of extubation failure, ICU and hospital mortality, tracheotomies, septic complications, days and rates of continuous sedation, and ICU length of stay were not significantly different between the two groups. CONCLUSIONS In a highly experienced centre NIV may be used to facilitate discontinuation of mechanical ventilation in selected patients with resolving hypoxemic ARF.


Phylogeny of the SARS coronavirus.


title: Investigation of diarrhea in AIDS.

text: Chronic diarrhea is a common problem in patients with acquired immune deficiency syndrome (AIDS), resulting in significant morbidity and potential mortality. In the early stages of immunodeficiency, human immunodeficiency virus (HIV)-infected patients are susceptible to infection with the same enteric pathogens that cause diarrhea in immunocompetent hosts, but with progressive immunodeficiency, these patients become susceptible to numerous opportunistic disorders. The main factor to consider when tailoring the work-up of diarrhea in the HIV-infected patient is the immune status, which is reflected by the total CD4 lymphocyte cell count. A CD4 count of less than 100 cells/microL is significantly correlated with opportunistic disorders. For the HIV-infected patient with diarrhea, repeated stool studies to investigate for bacteria, ova and parasites should be the first step. When either upper or lower gastrointestinal tract symptoms are present and stool studies are negative, endoscopy directed to the probable organ of involvement is appropriate. If localizing symptoms are absent, the most appropriate next test is sigmoidoscopy with biopsies. Not infrequently, despite extensive evaluation, the cause of diarrhea in patients with AIDS remains unexplained. Recently, the widespread use of highly active antiretroviral therapy, including protease inhibitors, has led to a change in the epidemiology of diarrhea in AIDS patients. As their immune status improves, HIV-infected patients treated with combination therapy become less prone to opportunistic disorders. However, diarrhea appears to be frequent because several antiretroviral agents can themselves cause diarrhea.


title: The organ tropism of mouse hepatitis virus A59 in mice is dependent on dose and route of inoculation.

text: The organ tropism of MHV-A59, a murine coronavirus, was studied in 4-6 week-old C57BL/6 mice inoculated by different routes and with various amounts of virus. MHV-A59 caused hepatitis after intracerebral and intraperitoneal inoculation (two clearly artificial routes) and also after intranasal and intragastric inoculation (two routes more likely to mimic naturally acquired infection). For each route, the severity of hepatitis was dependent on the amount of virus inoculated. Significantly higher doses were needed to cause hepatitis by the intranasal or intragastric routes. We have shown previously that mice inoculated intracerebrally with MHV-A59 develop mild meningoencephalitis followed by chronic central nervous system (CNS) disease, characterized by primary demyelination (1). We extend these results here to show that acute CNS disease can be produced also by intranasal and intragastric inoculation, although much larger doses are needed as compared to intracerebral inoculation. Thus induction of demyelination, not only by the intracerebral route but also by the intranasal route, provides a useful model system to study virus-induced demyelination.


title: Immunomodulatory effects in vivo of recombinant porcine interferon gamma on leukocyte functions of immunosuppressed pigs.

text: Immunological parameters of porcine peripheral blood mononuclear cells after in vivo injections of recombinant porcine interferon gamma (rPoIFN gamma) were studied in pigs immunosuppressed by dexamethasone (6 mg/kg body weight in a single injection). A 2-d period of rPoIFN gamma injected alone and intramuscularly at a dose of 1 microgram/kg body weight increased interleukin 1 (IL1) production (P less than 0.05). Recombinant porcine IFN gamma also reversed the immunosuppressive effects of dexamethasone on: i), lymphocyte responsiveness to mitogens: PHA (P less than 0.03), ConA (P less than 0.053); ii), IL1 production; and iii), IL2 production (P less than 0.05). However, rPoIFN gamma had no effect on neutrophilia induced by dexamethasone. These data show that rPoIFN gamma modulates leukocyte functions of pigs in vivo.


title: Identification and characterization of a virus-inducible non-coding RNA in mouse brain.

text: Infection of mice with Japanese encephalitis virus or Rabies virus results in the activation of a gene encoding a novel, non-coding RNA (ncRNA) in the mouse central nervous system. This transcript, named virus-inducible ncRNA (VINC), is identical to a 3.18 kb transcript expressed in mouse neonate skin (GenBank accession no. AK028745) that, together with a number of unannotated cDNAs and expressed sequence tags, is grouped in the mouse unigene cluster Mm281895. VINC is expressed constitutively in early mouse embryo and several adult non-neuronal mouse tissues, as well as a murine renal adenocarcinoma (RAG) cell line. Northern blotting of nuclear and cytoplasmic RNAs revealed that VINC is localized primarily in the nucleus of RAG cells and is thus a novel member of the nuclear ncRNA family.


title: Development of high-specificity antibodies against renal urate transporters using genetic immunization.

text: Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1). Antibodies against these transporters are very important for investigating their expressions and functions. With the cytokine gene as a molecular adjuvant, genetic immunization-based antibody production offers several advantages including high specificity and high recognition to the native protein compared with current methods. We fused high antigenicity fragments of the three transporters to the plasmids pBQAP-TT containing T-cell epitopes and flanking regions from tetanus toxin, respectively. Gene gun immunization with these recombinant plasmids and two other adjuvant plasmids, which express granulocyte/ macrophage colony-stimulating factor and FMS-like tyrosine kinase 3 ligand, induced high level immunoglobulin G antibodies, respectively. The native corresponding proteins of URAT1, OAT1 and OAT3, in human kidney can be recognized by their specific antibodies, respectively, with Western blot analysis and immunohistochemistry. Besides, URAT1 expression in Xenopus oocytes can also be recognized by its corresponding antibody with immuno-fluorescence. The successful production of the antibodies has provided an important tool for the study of UA transporters.


title: Evidence from multiplex molecular assays for complex multipathogen interactions in acute respiratory infections.

text: While most diagnostic processes cease with the detection of the first relevant infectious agent, newer multiplexed molecular methods which provide simultaneous analysis of multiple agents may give a more accurate representation of the true pathogen spectrum in these samples. To examine this in the context of respiratory infections, acute-phase respiratory specimens submitted to our clinical diagnostic microbiology/virology laboratory for our routine VIRAP diagnosis protocol during the spring 2006 peak respiratory infection season were processed in parallel by analysis with Genaco (QiaPlex) ResPlex I and ResPlex II molecular diagnostic panels. A total of 1,742 specimens were examined for 21 relevant targets each. The resulting data reveal that multiple infections are frequent and provide evidence for complex interactions between different infectious agents. Statistically relevant association patterns (both positive and negative) were observed between particular pathogens. While some interactions we observed are substantiated by prior reports in the literature, several specific patterns do not appear to have been reported previously. In addition, we report preliminary clinical evidence which supports a hypothesis that these coinfections are medically relevant and that effective treatment for severe respiratory tract infections will increasingly require diagnosis of all involved pathogens, as opposed to single-pathogen reporting.


Hemagglutinin-esterase glycoprotein gene of bovine corona virus delivered by adenovirus vector induces mucosal immunity in cotton rats.


The molecular pathogenesis of Semliki Forest virus: a model virus made useful?


title: [Managing patients in dialysis and with kidney transplant infected with Covid-19].

text: We are in the midst of a health emergency that is totally new for us all and that requires a concerted effort, especially when it comes to safeguarding patients on hemodialysis, and kidney transplant recipients. Brescia is currently a very active cluster of infections (2918 cases on the 17/03/2020), second only to Bergamo. The way our structure is organised has allowed us to treat nephropathic patients directly within the Nephrology Unit, following of course a great deal of reshuffling; at the moment, we are treating 21 transplanted patients and 17 on hemodialysis. This has led us to adopt a systematic approach to handling this emergency, not only in managing inpatients, but also in researching the new disease. Our approach is mirrored in the guidelines attached to this article, originally intended for internal use only but potentially very useful to our colleagues, as they face the same exact problems. We have also started collecting data on our positive patients with the aim of understanding better the functioning of this disease and how best to manage it. If anyone is interested, we ask you to please get in touch with us, so we can coordinate our efforts.


title: Effect of experimental genital mycoplasmosis on production of matrix metalloproteinases in membranes and amniotic fluid of Sprague-Dawley rats.

text: PROBLEM Preterm, premature rupture of membranes (PPROM) is a dire pregnancy outcome that is frequently associated with infection by the genital mycoplasmas, Mycoplasma hominis, Ureaplasma parvum, and U. urealyticum. One potential mechanism by which these microorganisms may cause PPROM is by increasing the concentration of matrix metalloproteinases (MMPs) in the membranes and amniotic fluid. We tested this hypothesis in a well-defined model system of genital infection with M. pulmonis, a natural reproductive pathogen of rats. METHOD OF STUDY Timed-pregnant, specific pathogen-free, Sprague-Dawley rats were infected with 10(7) CFU M. pulmonis at gestation day (gd) 14. Controls received an equivalent volume (100 microL) of sterile medium. At gd 18, rats were euthanized, and membranes and amniotic fluids were harvested and stored at -70 degrees C until analysis. Proteinase activity of amniotic fluid and membranes was resolved on discontinuous 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis gelatin zymography gels. Band intensity was determined using a digital gel documentation system and the manufacturer's software (Kodak). RESULTS Gelatinolytic activity associated with a band similar in molecular weight to ProMMP-9 (92 kDa, the inactive precursor of MMP-9) was significantly increased in amniotic fluids and membranes harvested from M. pulmonis-treated pups at gd 18 when compared with tissues harvested from control pups. Both ProMMP-9 and ProMMP-2 (72 kDa, the inactive precursor of MMP-2) were increased in infected animals at gd 21. CONCLUSION Our study suggests that the genital mycoplasmas can increase MMP-9 production in vivo.


title: Caring for a surge of Hurricane Katrina evacuees in primary care clinics.

text: Primary care physicians are rarely mentioned in medical disaster plans. We describe how a group of mostly family physicians and administrators of the JPS Health Network (JPS) took primary responsibility for 3,700 evacuees of Hurricane Katrina who came to Tarrant County, Texas. JPS provided medical care to 1,664 (45%) evacuees during a 2-week period. The most common needs were medications for chronic illnesses and treatment of skin infections (primarily on the feet). The JPS Emergency Department saw only 148 evacuees, most of whom arrived by their own transportation and were not seriously ill. JPS created a triage center located several miles from the hospital that referred almost all evacuees with health care needs to a primary care clinic. It was an effective approach for caring for the medical needs of disaster victims and prevented an emergency department and hospital from being overwhelmed. The JPS experience may guide future planning efforts for natural or manmade disasters, especially pandemic threats.


title: CD4 T-cell-mediated demyelination is increased in the absence of gamma interferon in mice infected with mouse hepatitis virus.

text: Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. Adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected mice deficient in recombination activation gene 1 resulted in demyelination. We showed previously that the process of CD8 T-cell-mediated demyelination was strongly dependent on the expression of gamma interferon (IFN-gamma) by donor cells. In this report, we show, in contrast, that demyelination and lymphocyte infiltration were increased in recipients of IFN-gamma(-/-) CD4 T cells when compared to levels in mice receiving C57BL/6 CD4 T cells.


title: Animal origins of SARS coronavirus: possible links with the international trade in small carnivores.

text: The search for animal host origins of severe acute respiratory syndrome (SARS) coronavirus has so far remained focused on wildlife markets, restaurants and farms within China. A significant proportion of this wildlife enters China through an expanding regional network of illegal, international wildlife trade. We present the case for extending the search for ancestral coronaviruses and their hosts across international borders into countries such as Vietnam and Lao People's Democratic Republic, where the same guilds of species are found on sale in similar wildlife markets or food outlets. The three species that have so far been implicated, a viverrid, a mustelid and a canid, are part of a large suite of small carnivores distributed across this region currently overexploited by this international wildlife trade. A major lesson from SARS is that the underlying roots of newly emergent zoonotic diseases may lie in the parallel biodiversity crisis of massive species loss as a result of overexploitation of wild animal populations and the destruction of their natural habitats by increasing human populations. To address these dual threats to the long-term future of biodiversity, including man, requires a less anthropocentric and more interdisciplinary approach to problems that require the combined research expertise of ecologists, conservation biologists, veterinarians, epidemiologists, virologists, as well as human health professionals.


title: Factors influencing compliance with quarantine in Toronto during the 2003 SARS outbreak.

text: The purpose of this study was to cull lessons from Toronto's experiences with large-scale quarantine during the outbreak of Severe Acute Respiratory Syndrome in early 2003. We focused on issues that affected the population's willingness to comply with quarantine. Information was acquired from interviews, telephone polling, and focus groups. Issues of quarantine legitimacy, criteria for quarantine, and the need to allow some quarantined healthcare workers to leave their homes to go to work were identified. Also important was the need to answer questions from people entering quarantine about the continuation of their wages, salaries, and other forms of income while they were not working, and about the means by which they would be supplied with groceries and other services necessary for daily living. The threat of enforcement had less effect on compliance than did the credibility of compliance-monitoring. Fighting boredom and other psychological stresses of quarantine, muting the forces of stigma against those in quarantine, and crafting and delivering effective and believable communications to a population of mixed cultures and languages also were critical. The need for officials to develop consistent quarantine policies, procedures, and public messages across jurisdictional boundaries was paramount.


Aquagenic Syringeal Acrokeratoderma from Extensive Water Immersion during the COVID-19 Pandemic Outbreak.


title: New modification of cephalic resection of lateral crus in endonasal rhinoplasty.

text: A successful rhinoplasty mainly depends on maintaining adequate nasal tip projection and achieving the desired tip refinement. In endonasal rhinoplasty, the surgeon can modify the tip anatomy while still preserving the key structural support mechanisms. Herein, we describe a new modification of retrograde technique for the resection of the cephalic margin of the lateral crus in endonasal rhinoplasty in which a combined resection of the cephalic margin of the lateral crus and its underlying mucoperichondrium are performed.


title: [Modeling of the SARS coronavirus main proteinase and conformational flexibility of the active site].

text: SARS coronavirus 3CL proteinase is the key enzyme for virus replication which may serve as the target for drug discovery against SARS. A 3D structure model has been built for SARS coronavirus 3CL proteinase by comparative protein modeling. A homodimer model of the proteinase was also built. Analysis of the dimeric interface suggests the 3CL proteinase may have dimer form in solution. The conformational flexibility of the active site has been simulated by molecular dynamics combined with multi-canonical sampling. The active site loops have two typical conformations which may be related to the conformational movement associated with the enzymatic reaction.


The persistence and resurgence of medical pluralism.


title: Coronavirus antibodies in sera from patients with multiple sclerosis and matched controls.

text: Sera from patients with multiple sclerosis and carefully matched controls were tested for antibodies to three strains of coronavirus. There was no significant difference in the levels of antibody in the patients vs the controls. We conclude that unless the strains of coronaviruses recently reported to have been isolated from patients with multiple sclerosis express important serological differences from those used in these studies, coronaviruses are not associated with the cause of multiple sclerosis.


title: Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial.

text: CONTEXT Immune response in elderly individuals has been reported to improve after micronutrient supplementation. However, efficacy trials evaluating infectious diseases as outcomes are scarce and inconclusive. OBJECTIVE To investigate the effect of daily multivitamin-mineral and vitamin E supplementation on incidence and severity of acute respiratory tract infections in elderly individuals. DESIGN A randomized, double blind, placebo-controlled, 2 x 2 factorial trial. SETTING AND PARTICIPANTS A total of 652 noninstitutionalized individuals aged 60 years or older enrolled from 2 community-based sampling strategies in the Wageningen area of the Netherlands, conducted from 1998 to 2000. At baseline, 6% of participants had suboptimal ascorbic acid and 1.3% had suboptimal alpha-tocopherol plasma concentration. INTERVENTION Physiological doses of multivitamin-minerals, 200 mg of vitamin E, both, or placebo. MAIN OUTCOME MEASURES Incidence and severity of self-reported acute respiratory tract infections at 15 months, as assessed by a nurse (telephone contact), home visits, and microbiological and serological testing in subsets of patients. RESULTS During a median observation period of 441 days, 443 (68%) of 652 participants recorded 1024 respiratory tract infection episodes. The incidence rate ratio of acute respiratory tract infection for multivitamin-mineral supplementation was 0.95 (95% confidence interval, 0.75-1.15; P =.58) and for vitamin E supplementation, 1.12 (95% confidence interval, 0.88-1.25; P =.21). Severity of infections was not influenced by multivitamin-mineral supplementation. For vitamin E vs no vitamin E, severity was worse: median (interquartile range) for illness-duration was 19 (9-37) vs 14 (6-29) days, P =.02; number of symptoms, 6 (3-8) vs 4 (3-8), P =.03; presence of fever, 36.7% vs 25.2%, P =.009; and restriction of activity, 52.3% vs 41.1%, P =.02. CONCLUSIONS Neither daily multivitamin-mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favorable effect on incidence and severity of acute respiratory tract infections in well-nourished noninstitutionalized elderly individuals. Instead we observed adverse effects of vitamin E on illness severity.


title: Development of diabetes in Chinese with the metabolic syndrome: a 6-year prospective study.

text: OBJECTIVE We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. RESEARCH DESIGN AND METHODS We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose > or =7.0 mmol/l with fasting and/or > or =11.1 mmol/l at 2 h. RESULTS The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8-6.0] and 3.5 [2.3-5.2], respectively. HRs for fasting plasma glucose (FPG) > or =6.1 or 5.6 mmol/l were 6.9 [4.1-11.5] and 4.1 [2.8-6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, approximately 20%, but their negative predictive values were approximately 95%. CONCLUSIONS The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes.


title: Acid gastroesophageal reflux in convalescent preterm infants: effect of posture and relationship to apnea.

text: Concerns regarding gastroesophageal reflux (GER) and associated apnea episodes result in some practitioners having convalescent, prematurely born infants sleep in the prone position. We have tested the hypothesis that such infants would not suffer from clinically important acid GER or associated apnea episodes more in the supine compared with the prone position. Lower esophageal pH was measured and videopolysomnographic recordings of nasal airflow, chest and abdominal wall movements, electrocardiographic activity, and oxygen saturation were made on two successive days of 21 premature infants (median gestational age 28 wk) at a median postmenstrual age (PMA) of 36 wk. On each day, the infants were studied prone and supine. The acid reflux index was higher in the supine compared with the prone position (median 3% versus 0%, p = 0.002), but was low in both positions. The number of obstructive apnea episodes per hour was higher in the supine position (p = 0.008). There were, however, no statistically significant correlations between the amount of acid GER and the number of either obstructive or total apnea episodes in either the supine or prone position. Supine compared with prone sleeping neither increases clinically important acid GER nor obstructive apnea episodes associated with acid GER in asymptomatic, convalescent, prematurely born infants.


title: Characteristics associated with HIV infection among heterosexuals in urban areas with high AIDS prevalence --- 24 cities, United States, 2006-2007.

text: In the United States, approximately one in three new human immunodeficiency virus (HIV) infections are transmitted via heterosexual contact. To monitor HIV risk behaviors and HIV prevalence among heterosexuals and other populations, CDC surveys persons in selected metropolitan statistical areas (MSAs), using the National HIV Behavioral Surveillance System (NHBS). This report summarizes data collected from heterosexuals in 24 MSAs with a high prevalence of acquired immunodeficiency syndrome (AIDS) that participated in NHBS during 2006-2007. Of 14,837 heterosexuals aged 18-50 years who were interviewed and tested, 2.0% were HIV infected. HIV prevalence was higher among those with lower socioeconomic status (SES). For example, HIV prevalence was 2.8% among participants with less than a high school education compared with 1.2% among those with more than a high school education, 2.6% among participants who were unemployed compared with 1.0% among those who were employed, and 2.3% among participants with annual household incomes at or below the poverty level compared with 1.0% among those with incomes above the poverty level. This association between HIV prevalence and SES could not be attributed to factors commonly associated with HIV infection risk in heterosexuals, such as using crack cocaine, exchanging sex for things such as money or drugs, or being diagnosed with a sexually transmitted disease (STD). Based on the association observed between HIV prevalence and SES, HIV prevention activities targeted at heterosexuals in urban areas with high AIDS prevalence should be focused on those with lower SES.


title: New filtering antimicrobial nonwovens with various carriers for biocides as respiratory protective materials against bioaerosol.

text: This study evaluated the bioactivity of polypropylene melt-blown filtering nonwovens used in respiratory protective devices (RPD) with a biocidal agent (alkylammonium microbiocides) on 2 mineral carriers. Two types of carriers were tested: a bentonite, with an aluminosilicate base, and a perlite, volcanic glass. High biostatic and biocidal effects of modified nonwovens with biocides were tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. Nonwovens modified with a biocide on a bentonite carrier showed an opposite reaction to a biocide on a perlite. The research also showed that 10% concentration of a biocidal agent on a perlite carrier was sufficient to inhibit the growth of bacteria (100% reduction) placed in the structure of a filtering material during normal use of RPD. A comparison of the biological activity of 2 filtering materials, each containing 10% of a perlite and produced in a laboratory and industrial conditions, showed no statistically significant differences.


title: Simple solution for preventing cerebrospinal fluid loss and brain shift during multitrack deep brain stimulation surgery in the semisupine position: polyethylene glycol hydrogel dural sealant capping: rapid communication.

text: This study evaluated preliminary findings on the efficacy of polyethylene glycol (PEG) hydrogel dural sealant capping for the prevention of cerebrospinal fluid (CSF) leakage and pneumocephalus during deep brain stimulation (DBS) surgery in the semisupine position. Group A consisted of 5 patients who underwent bilateral subthalamic nucleus (STN)-DBS surgery without PEG hydrogel dural sealant capping. Group B consisted of 5 patients who underwent bilateral STN-DBS surgery with PEG hydrogel dural sealant capping. The immediate postoperative intracranial air volume was measured in all patients and compared between the 2 groups using the Welch test. Adverse effects were also examined in both groups. The intracranial air volume in Group A was 32.3 ± 12.3 ml (range 19.1-42.5 ml), whereas that in Group B was 1.3 ± 1.5 ml (range 0.0-3.5 ml), showing a significant difference (p < 0.005). No hemorrhage or venous air embolisms were observed in either group. The effect of brain shift was discriminated by STN recordings in Group B. These preliminary findings indicate that PEG hydrogel dural sealant capping may reduce adverse effects related to CSF leakage and brain shift during DBS surgery.


WHO recommended measures for persons undertaking international travel from areas affected by severe acute respiratory syndrome (SARS).


title: Dipeptidyl peptidase-4 inhibition and renoprotection: the role of antifibrotic effects.

text: PURPOSE OF REVIEW This article analyzes the potential beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors on renal diseases. RECENT FINDINGS The pathological significance of DPP-4, either dependent or independent on catalytic activities, on renal diseases has been reported in preclinical studies. With regard to this, we have shown that damaged endothelial cells are converted to a mesenchymal cell phenotype, which is associated with the induction of DPP-4 in endothelial cells. The endothelial mesenchymal transition may contribute to kidney fibrosis; indeed, the antifibrotic effects of DPP-4 inhibitors have been reported elsewhere. However, even though such potential benefits of DPP-4 inhibitors on renal diseases were shown in preclinical studies, clinical trials have not yet revealed significant benefits in renal hard outcomes of DPP-4 inhibitors. SUMMARY To completely understand the beneficial effects of DPP-4 inhibitors, both the following studies are required: first, preclinical studies that analyze deeper molecular mechanisms of DPP-4 inhibition, and, second, clinical studies that investigate whether such potential beneficial effects of DPP-4 inhibitors are relevant to the patients in the clinic.


title: Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates.

text: Nucleoside monophosphates and monophosphonates have been known for a long time to exert favorable pharmacological effects upon intracellular delivery. However, their development as drug molecules has been hindered by the inherent poor druglike properties of the monophosphate and monophosphonate groups. These include inefficient cellular uptake and poor in vivo stability, with this latter drawback being most relevant to monophosphates than monophosphonates. To address these limitations, numerous monophosphate and monophosphonate prodrug strategies have been developed and applied in the discovery of nucleoside monophosphate and monophosphonate prodrugs that can treat viral infections and cancer. The approval of sofosbuvir, a nucleoside monophosphate prodrug, highlighted the success to be had by employing these prodrug technologies in the discovery of nucleotide therapeutics. In this Miniperspective, we discuss the different key monophosphate and monophosphonate nucleoside prodrugs that entered clinical development, some of which may in the future be approved to treat various human diseases.


title: The Sulu-Sulawesi Sea: environmental and socioeconomic status, future prognosis and ameliorative policy options.

text: The Sulu-Sulawesi Sea, with neighboring Indonesian Seas and South China Sea, lies at the center of the world's tropical marine biodiversity. Encircled by 3 populous, developing nations, the Philippines, Indonesia and Malaysia, the Sea and its adjacent coastal and terrestrial ecosystems, supports ca. 33 million people, most with subsistence livelihoods heavily reliant on its renewable natural resources. These resources are being impacted severely by rapid population growth (> 2% yr-1, with expected doubling by 2035) and widespread poverty, coupled with increasing international market demand and rapid technological changes, compounded by inefficiencies in governance and a lack of awareness and/or acceptance of some laws among local populations, particularly in parts of the Philippines and Indonesia. These key root causes all contribute to illegal practices and corruption, and are resulting in severe resource depletion and degradation of water catchments, river, lacustrine, estuarine, coastal, and marine ecosystems. The Sulu-Sulawesi Sea forms a major geopolitical focus, with porous borders, transmigration, separatist movements, piracy, and illegal fishing all contributing to environmental degradation, human suffering and political instability, and inhibiting strong trilateral support for interventions. This review analyzes these multifarious environmental and socioeconomic impacts and their root causes, provides a future prognosis of status by 2020, and recommends policy options aimed at amelioration through sustainable management and development.


title: Bovine viral diarrhea virus isolated from fetal calf serum enhances pathogenicity of attenuated transmissible gastroenteritis virus in neonatal pigs.

text: A bovine viral diarrhea virus (BVDV-C) was isolated from swine tissue culture cells used to attenuate the transmissible gastroenteritis virus (TGEV) after 68 passes. Piglets given a pure culture of BVDV-C developed clinical signs similar to those of a mild TGEV infection and recovered by 10 days postexposure. Villous blunting and fusion was observed in the small intestine, and a lymphocyte depletion was observed in Peyer's patches in the ileum. Piglets given a combination of BVDV-C and attenuated TGEV developed clinical signs similar to those of a virulent TGEV infection and were euthanized. The combined infection induced a generalized lymphocyte depletion throughout the lymphatic system and villous atrophy in the intestinal tract. Piglets exposed to a another type I strain of BVDV (NY-1) either alone or in combination with the attenuated TGEV had mild clinical signs similar to those of a TGEV infection. Moderate villous atrophy in the ileum and a lymphocyte depletion in the mesenteric lymph node were observed in these piglets postmortem. The data indicate a potential problem for diagnostic laboratories in relation to a diagnosis of virulent TGEV infections and in the field for young piglets exposed to a BVDV-contaminated TGEV vaccine.


title: The control of necrotic enteritis in sucking piglets by means of a Clostridium perfringens toxoid vaccine.

text: Necrotic enteritis in sucking piglets constitutes a serious problem in piglet rearing units because of the high morbidity and mortality associated with the disease. The primary causal agent is Clostridium perfringens type C. The beta-toxin plays a decisive role in the pathogenesis of this disease. A toxoid vaccine for use in sows has been developed and studied in field trials. The European Pharmacopoeia Monograph on vaccines for use in animals lays down a method of the efficacy testing based on the immunization of rabbits, the collection of pooled sera and the subsequent assay of anti-toxin antibodies in mice using an appropriate test toxin. The vaccine is regarded as effective if it induces a minimum of 10 IU of beta-anti-toxin per ml of rabbit serum. We have established a range of 17.14-98.23 IU beta-anti-toxin per ml rabbit serum induced by a sample of C. perfringens toxoid vaccine. The vaccine has been used under field conditions in different rearing units at the same time, mostly in the form of emergency vaccinations following the outbreak of disease. The outcome of vaccination was evaluated by recording the total numbers of piglets born alive and the piglet losses. Use of the vaccine, coupled with other measures, resulted in an approximately 30% reduction in the number of losses.


Communicating risks.


title: The ACE2 gene: its potential as a functional candidate for cardiovascular disease.

text: The RAS (renin-angiotensin system) plays an important role in the pathophysiology of CVD (cardiovascular disease), and RAS blockade is an important therapeutic strategy in the management of CVD. A new counterbalancing arm of the RAS is now known to exist in which ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Altered ACE2 expression is associated with cardiac and vascular disease in experimental models of CVD, and ACE2 is increased in failing human hearts and atherosclerotic vessels. In man, circulating ACE2 activity increases with coronary heart disease, as well as heart failure, and a large proportion of the variation in plasma ACE2 levels has been attributed to hereditary factors. The ACE2 gene maps to chromosome Xp22 and this paper reviews the evidence associating ACE2 gene variation with CVD and considers clues to potential functional ACE2 variants that may alter gene expression or transcriptional activity. Studies to date have investigated ACE2 gene associations in hypertension, left ventricular hypertrophy and coronary artery disease, but the results have been inconsistent. The discrepancies may reflect the sample size of the studies, the gender or ethnicity of subjects, the cardiovascular phenotype or the ACE2 SNP investigated. The frequent observation of apparent sex-dependence might be of special importance, if confirmed. As yet, there are no studies to concurrently assess ACE2 gene polymorphisms and circulating ACE2 activity. Large-scale carefully conducted clinical studies are urgently needed to clarify more precisely the potential role of ACE2 in the CVD continuum.


title: Reconstituted coronavirus TGEV virosomes lose the virus ability to induce porcine interferon-alpha production.

text: The transmissible gastroenteritis virus (TGEV) is a coronavirus which induces a strong interferon-alpha (IFN-alpha) production in vivo and in vitro. Previous studies have shown that the TGEV external protein M plays a major role in IFN-alpha induction by a non-infectious virus, whereas protein S is not involved. The present study extended these results by showing that monoclonal antibodies (MAbs) directed at the external viral protein sM could not block IFN-alpha induction, which argues against a direct role for this protein. In the same type of blocking experiment, MAbs to the TGEV receptor aminopeptidase N did not inhibit IFN-alpha induction, which strongly indicates that viral replication or entry through the receptor is not needed for TGEV induction of IFN-alpha in leukocytes. In an attempt to isolate functional envelope proteins, TGEV virions were detergent-solubilized and reconstituted in virosomes. Although BIAcore antigenic analysis revealed that the three external viral proteins were present on the virosomes, these proteins were unable to induce IFN-alpha in porcine leukocytes, and seemed to compete with the native virus for IFN-alpha induction. These data indicated that IFN-alpha inducing interactions between TGEV external proteins and leukocytes required a complex native envelope protein structure which has been lost in the virosomes.


title: In vitro interaction of coronaviruses with primate and human brain microvascular endothelial cells.

text: Primary human and primate brain microvascular endothelial cells were tested for permissiveness to coronaviruses JHM and 229E. While sub-genomic viral RNAs could be detected up to 72 hours post-infection, primate cells were abortively infected and neither virus caused cytopathology. Human cells were non-permissive for JHM but permissive for 229E replication; peak production of progeny 229E and observable cytopathic effects occurred approximately 22 and 32 hour post-infection, respectively. Using the criterion of cytopathology induction in infected endothelial cells, 229E was compared to other human RNA and DNA viruses. In addition, virus induced modulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and HLA I was monitored by immunostaining of infected cells.


Risks from microbes on the rise: reasons why and ways to prevent future epidemics.


title: Effect of the SARS outbreak on visits to a community hospital emergency department.

text: OBJECTIVES To examine the effect of severe acute respiratory syndrome (SARS) on visits to a community hospital emergency department (ED) during the early stage of the Toronto outbreak in 2003 and for the same period in 2004. We focused on visits for respiratory illness (SARS-like symptoms) and different age groups. METHODS This study is a retrospective review of ED discharge diagnoses obtained from a computerized database, examining the 4-week period starting March 28 for the years 2001-2004. We obtained the discharge diagnosis, age and visit date for each ED patient during the relevant time intervals, then compared visit data from 2003 and 2004 with a baseline derived from the average number of visits during 2001 and 2002. We constructed groupings based on age and respiratory-illness symptoms. RESULTS During the SARS outbreak in 2003, ED visits declined by 21% (95% confidence interval [CI], 18%-24%) over the 4-week study period. The greatest reduction was for combined infant and toddler visits (69%; 95% CI, 58%-79%); these did not recover the following year. However, during the SARS outbreak there was a large increase in the number of visits for respiratory illnesses in adults (61%; 95% CI, 46%-75%) and in teenagers (132%; 95% CI, 82%-182%). CONCLUSIONS During the SARS outbreak, total ED visits fell. The relative decline was most notable for infants and toddlers. By contrast, there was an increase in respiratory illness-related visits for adults and teenagers. In 2004, the year following the SARS outbreak, visit patterns shifted toward baseline levels, but ED visits by infants and toddlers remained depressed.


title: SARS Immunity and Vaccination.

text: Severe acute respiratory syndrome (SARS) is a serious and fatal infectious disease caused by SARS coronavirus (SARS-Cov), a novel human coronavirus. SARS-Cov infection stimulates cytokines (e.g., IL-10, IFN-gamma, IL-1, etc.) expression dramatically, and T lymphocytes and their subsets CD4(+) and CD8(+) T cells are decreased after onset of the disease. SARS-specific IgG antibody is generated in the second week and persists for a long time, whereas IgM is expressed transiently. The spike protein and neucleocapsid protein are most abundant in SARS-Cov and contribute dominantly to the antibody production during the course of disease. Spike protein, especially the ACE-2 binding region (318-510aa) is capable of producing neutralizing antibody to SARS-Cov. Neucleocapsid protein induces protective specific CTL to SARS-Cov. Therefore, applications with spike subunit, neucleocapsid subunit as well as inactivated SARS-Cov are three prospective vaccination strategies for SARS.


title: Absence of the p55 Kd TNF-alpha receptor promotes survival in rabies virus acute encephalitis.

text: We investigated the role played by inflammation in acute encephalitis following infection with a neurotropic virus by comparing the disease caused by the CVS strain of rabies virus in C57BL/6 and mice deficient for the p55 Kd TNF-alpha receptor (p55TNFR-/-). Morbidity (weight loss and paralysis) and mortality of infected mice were associated with viral propagation, cytokine (IL-6, IL-10, TNF-alpha and IFN-gamma) production, induction of apoptosis and infiltration of inflammatory cells. Mortality occurred later in p55TNFR-/- (than in C57BL/6 mice. In contrast, morbidity and the number of cells undergoing apoptosis were similar in C57BL/6 and p55TNFR-/- mice.) This suggests that morbidity and mortality are independently regulated and that the death of the animal was not due to CNS apoptosis. Delayed mortality correlated with: a reduction in viral load on day 9 p.i., an increase in IFN-gamma and IL-10 concentrations and a reduction in inflammatory cell infiltration in the CNS. Thus, these data indicate that CVS infection elicits an inflammatory response within the CNS and suggest that cytokines signaling via the p55 Kd TNF-alpha receptor is deleterious for the survival of the host. These results strongly suggest that, the modulation of TNF-alpha and upregulation of IFN-gamma would be a powerful anti-virus strategy in cases of viral encephalitis.


title: [Clinical observation on 103 patients of severe acute respiratory syndrome treated by integrative traditional Chinese and Western Medicine].

text: OBJECTIVE To observe the effect of 103 patients of severe acute respiratory syndrome (SARS) treated by integrative traditional Chinese and western medicine. METHODS Alimentotherapy, respiratory auxiliaring ventilation, anti-infective and glucocorticoid methods were used in western medicine; Chinese herbal medicine was used according to syndrome differentiation in traditional Chinese medicine. Descriptive statistical analyses were performed. RESULTS Of the 103 patients, 77 were identified as severe cases and 29 were admitted to the intensive care unit. A total of 96 patients (93.2%) were cured, 7 patients died (6.8%). The mean time between onset of feverishness and improvement was 6.72 +/- 3.95 days; 94 successful responses to therapy could be demonstrated by serial chest radiographs showing the resolution of lung opacities during 18.13 +/- 8.99 days, 2 of whom showed fibroid cord-like changes. CONCLUSION In terms of traditional Chinese medicine theory, SARS is referred to "infectious febrile disease", the therapeutic strategies of integrative traditional Chinese and western on SARS have been shown effective, and traditional Chinese medicine played a positive role in it.


title: Integrated CMOS amplifier for ENG signal recording.

text: The development and in vivo test of a fully integrated differential CMOS amplifier, implemented with standard 0.7-microm CMOS technology (one poly, two metals, self aligned twin-well CMOS process) intended to record extracellular neural signals is described. In order to minimize the flicker noise generated by the CMOS circuitry, a chopper technique has been chosen. The fabricated amplifier has a gain of 74 dB, a bandwidth of 3 kHz, an input noise of 6.6 nV/(Hz)0.5, a power dissipation of 1.3 mW, and the active area is 2.7 mm2. An ac coupling has been used to adapt the electrode to the amplifier circuitry for the in vivo testing. Compound muscle action potentials, motor unit action potentials, and compound nerve action potentials have been recorded in acute experiments with rats, in order to validate the amplifier.


title: Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma.

text: Brain tumors can arise following deregulation of signaling pathways normally activated during brain development and may derive from neural stem cells. Given the requirement for Hedgehog in non-neoplastic stem cells, we investigated whether Hedgehog blockade could target the stem-like population in glioblastoma multiforme (GBM). We found that Gli1, a key Hedgehog pathway target, was highly expressed in 5 of 19 primary GBM and in 4 of 7 GBM cell lines. Shh ligand was expressed in some primary tumors, and in GBM-derived neurospheres, suggesting a potential mechanism for pathway activation. Hedgehog pathway blockade by cyclopamine caused a 40%-60% reduction in growth of adherent glioma lines highly expressing Gli1 but not in those lacking evidence of pathway activity. When GBM-derived neurospheres were treated with cyclopamine and then dissociated and seeded in media lacking the inhibitor, no new neurospheres formed, suggesting that the clonogenic cancer stem cells had been depleted. Consistent with this hypothesis, the stem-like fraction in gliomas marked by both aldehyde dehydrogenase activity and Hoechst dye excretion (side population) was significantly reduced or eliminated by cyclopamine. In contrast, we found that radiation treatment of our GBM neurospheres increased the percentage of these stem-like cells, suggesting that this standard therapy preferentially targets better-differentiated neoplastic cells. Most importantly, viable GBM cells injected intracranially following Hedgehog blockade were no longer able to form tumors in athymic mice, indicating that a cancer stem cell population critical for ongoing growth had been removed. Disclosure of potential conflicts of interest is found at the end of this article.


Severe acute respiratory syndrome (SARS).


Pharyngitis and rheumatic fever.


title: Antibodies to human coronaviruses 229E and OC43 in the population of C.R.

text: Of 1200 human sera tested by enzyme-linked immunosorbent assay (ELISA), 53% contained antibodies to human coronavirus (HCV) 229E and 88% to HCV OC43. The sera were from persons aged 13 months to 80 years, both males and females, and were collected in four different regions in 1986. The percentage of positives increased with increasing age and tended to vary according to the geographic area. Additional paired human sera from 218 patients with acute respiratory diseases (ARD) were collected between October 1986 and June 1987 in Prague. Significant antibody rises to HCV strain 229E were detected in 7 (3.2%) patients 9 months to 17 years old, to HCV strain OC43 in 4 (1.8%) patients under 2 years of age.


title: Pathologic and immunohistochemical findings in a feline aortic body tumor.

text: The presence of a heart-base tumor was diagnosed by ultrasound imaging in a 10-year-old, female, domestic shorthaired cat presenting with dyspnea and pleural effusion because of the presence of a modified transudate. Hematology and clinical chemistry were unremarkable. The owner elected euthanasia. At necropsy, a locally extensive, firm, multilobulated nodule surrounded the pulmonary vein. The tumor was composed of lobules of large polygonal cells separated by a fine fibrovascular stroma. Tumor cells infiltrated the myocardium, and neoplastic emboli were present, but no metastases were macroscopically detectable. Tumor cells were immunohistochemically positive for chromogranin A, for synaptophysin and, faintly, for neuron-specific enolase and negative for vimentin, cytokeratin, alpha smooth muscle actin, glial fibrillary acidic protein, thyreoglobulin, and calcitonin. Based on histologic and immunohistochemical findings, the diagnosis of chemodectoma was made.


Doctors as fiduciaries: a legal construct of the patient-physician relationship.


Chromatography of mouse hepatitis virus replicative intermediate and replicative form RNA.


title: [De-escalation: Testicular cancer.]

text: OBJECTIVES To provide a priority algorithm for determinate diagnostic, therapeutic and follow-up procedures regarding at testicular cancer, adjusted by institutional requirements. Testicular cancer patient assessment during COVID-19 Pandemia. MATERIAL AND METHODS Review of relevant manuscript published up to date, draft creation correctedt hough modified nominal group until final corrected manuscript. RESULTS A lack of scientific evidence exists through a large amount of manuscripts. The authors support prioritizing diagnostic and therapeutic procedures. Once priorities have been established, that will facilitate providing each patients the limited resources. Initial diagnostic procedures for testicular cancer such as scrotal US, orchiectomy, staging CT and adjuvant treatment (if required) are priority. Reducing the usage of chemotherapy with respiratory toxicity and increasing the usage ofgrowth factors during chemotherapy treatment are the main stakeholders of treatment. Besides, providing active surveillance on non-risk factor clinical stage I is alsoa priority. In case of positive COVID-19, it is important to high light that the vast majority of patients are tentatively cured. CONCLUSIONS During de-escalation phases, patients diagnosed with testicular cancer should receive priority care during initial assessment. The follow-ups of patients with low -risk and without recurrence for a long time, might be delayed.


title: Investigation of the influencing factors on severe acute respiratory syndrome among health care workers.

text: OBJECTIVE To investigate the protective factors and risk factors of nosocomial infection of severe acute respiratory syndrome (SARS) among health care workers (HCWs), and thus provide the scientific basis for prevention and control of nosocomial infection. METHODS With the case-control study, a standardized questionnaire was used for data collection in three general hospitals where nosocomial infection had occurred. Univariate analysis was done at first. All concerned factors about SARS infection were scanned by using Chi-square test and Fisher's exact test one by one, and determined as to whether they were risk factors or protective factors according to odd ratio (OR) score. Then, multivariate unconditional logistic regression analysis was used to re-analyze the picked-out factors for finding out which factors played independent roles. RESULTS Twenty-two factors (nineteen protective factors and three risk factors), among the total fifty-six factors, were significantly associated with SARS infection. Multivariate unconditional logistic regression revealed that factors such as double exposure suits (OR=0.053), education (OR=0.072), gloves (OR=0.102), hands sterilized by iodine (OR=0.231), room air ventilation (OR=0.32), were significantly protective; conversely, tracheal intubation (OR=30.793) was a significant risk factor. CONCLUSION Strict defense and antisepsis measures were pivotal in preventing SARS infection among high-risk medical personnel. Education about associated knowledge and effective air ventilation were also important factors.


title: 7th EFIS Tatra Immunology Conference. Molecular determinants of T-cell immunity. 24-28 June 2006, High Tatra Mountains, Slovakia.

text: This meeting was hosted by the European Federation of Immunological Societies celebrating its 7th meeting in the High Tatra Mountains of Slovakia on 24-28 June 2006. Entitled molecular determinants of T-cell immunity, the meeting covered a wide range of novel methods to regulate an unwanted immune response in autoimmunity and boost the immune system to combat viral infection and cancer.


title: Hospitalisation associated with the 2009 H1N1 pandemic and seasonal influenza in Hong Kong, 2005 to 2010.

text: Reliable estimates of the morbidity burden caused by the 2009 pandemic influenza (pH1N1) are important for assessing the severity of the pandemic. Poisson regression models were fitted to weekly numbers of cause-specific hospitalisation in Hong Kong from 2005 to 2010. Excess hospitalisation associated with the 2009 pandemic and seasonal influenza was derived from the model by incorporating the proxy variables of weekly proportions of specimens positive for the pandemic influenza A(H1N1)pdm09, seasonal influenza A (subtypes H3N2 and H1N1) and B viruses. Compared with seasonal influenza, pH1N1 influenza was associated with higher hospitalisation rates for acute respiratory disease (ARD) among children younger than 18 years and adults aged between 18 and 64 years, but among the elderly aged 65 years and older the hospitalisation rates were lower for pH1N1 than for seasonal H3N2 and H1N1 influenza. Hospitalisation rates for chronic diseases associated with pH1N1 influenza were generally higher than those associated with seasonal influenza. The reported hospitalised cases with laboratory-confirmed pandemic infections accounted for only 16% of pH1N1 influenza-associated hospitalisations for ARD in the age group 75 years and older, and 5‒66% of hospitalisations for chronic diseases in those older than 40 years. The 2009 H1N1 influenza pandemic was associated with a dramatically increased risk of hospitalisation among children and young adults. The morbidity burden of pandemic was underreported in old people and in those with chronic conditions.


title: A model of viral wheeze in nonasthmatic adults: symptoms and physiology.

text: Episodic wheezing associated with viral infections of the upper respiratory tract (URT) is a common problem in young children but also occurs in adults. It is hypothesized that an experimental infection with human coronavirus (HCoV), the second most prevalent common cold virus, would cause lower respiratory tract (LRT) changes in adults with a history of viral wheeze. Twenty-four viral wheezers (15 atopic) and 19 controls (seven atopic) were inoculated with HCoV 229E and monitored for the development of symptoms, changes in airway physiology and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). At baseline, viral wheezers were similar to controls in PC20 (mean+/-SD log2PC20: 5.1+/-1.9 and 5.8+/-1.4 g x L(-1), respectively) but had a lower FEV1 than controls (mean+/-SD 85.8+/-11.4 and 95.6+/-13.2% predicted, respectively p < 0.05). Nineteen viral wheezers and 11 controls developed colds. Viral wheezers with colds reported significantly more URT symptoms than controls (median scores (interquartile range): 24 (10-37) and 6 (4-15), respectively p = 0.014). Sixteen viral wheezers and no controls reported LRT symptoms (wheeze, chest tightness and shortness of breath). The viral wheezers with colds had small (3-4%) reductions in FEV1 and peak expiratory flow on days with LRT symptoms (days 3-6), but a progressive reduction in PC20 from baseline on days 2, 4 and 17 after inoculation (by 0.82, 1.35 and 1.82 doubling concentrations, respectively). The fall in PC20 affected both atopic and nonatopic subjects equally. There were no changes in FEV1 or PC20 in controls. An adult model of viral wheeze that is independent of atopy and therefore, of classical atopic asthma was established.


title: Outbreaks of multidrug-resistant Pseudomonas aeruginosa in community hospitals in Japan.

text: We previously reported an outbreak in a neurosurgery ward of catheter-associated urinary tract infection with multidrug-resistant (MDR) Pseudomonas aeruginosa strain IMCJ2.S1, carrying the 6'-N-aminoglycoside acetyltransferase gene [aac(6')-Iae]. For further epidemiologic studies, 214 clinical isolates of MDR P. aeruginosa showing resistance to imipenem (MIC >or= 16 microg/ml), amikacin (MIC >or= 64 microg/ml), and ciprofloxacin (MIC >or= 4 microg/ml) were collected from 13 hospitals in the same prefecture in Japan. We also collected 70 clinical isolates of P. aeruginosa that were sensitive to one or more of these antibiotics and compared their characteristics with those of the MDR P. aeruginosa isolates. Of the 214 MDR P. aeruginosa isolates, 212 (99%) were serotype O11. We developed a loop-mediated isothermal amplification (LAMP) assay and a slide agglutination test for detection of the aac(6')-Iae gene and the AAC(6')-Iae protein, respectively. Of the 212 MDR P. aeruginosa isolates, 212 (100%) and 207 (98%) were positive in the LAMP assay and in the agglutination test, respectively. Mutations of gyrA and parC genes resulting in amino acid substitutions were detected in 213 of the 214 MDR P. aeruginosa isolates (99%). Of the 214 MDR P. aeruginosa isolates, 212 showed pulsed-field gel electrophoresis patterns with >or=70% similarity to that of IMCJ2.S1 and 83 showed a pattern identical to that of IMCJ2.S1, indicating that clonal expansion of MDR P. aeruginosa occurred in community hospitals in this area. The methods developed in this study to detect aac(6')-Iae were rapid and effective in diagnosing infections caused by various MDR P. aeruginosa clones.