title: Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community.

text: BACKGROUND Acute lower respiratory tract illness in previously well adults is usually labelled as acute bronchitis and treated with antibiotics without establishing the aetiology. Viral infection is thought to be the cause in most cases. We have investigated the incidence, aetiology, and outcome of this condition. METHODS Previously well adults from a stable suburban population consulting over one year with a lower respiratory tract illness were studied. For the first six months detailed investigations identified predetermined direct and indirect markers of infection. Evidence of infection was assessed in relation to presenting clinical features, indirect markers of infection, antibiotic use, and outcome. RESULTS Consultations were very common, particularly in younger women (70/1000 per year in previously well women aged 16-39 years), mainly in the winter months; 638 patients consulted, of whom 316 were investigated. Pathogens were identified in 173 (55%) cases: bacteria in 82 (Streptococcus pneumoniae 54, Haemophilus influenzae 31, Moraxella catarrhalis 7), atypical organisms in 75 (Chlamydia pneumoniae 55, Mycoplasma pneumoniae 23), and viruses in 61 (influenza 23). Seventy nine (24%) had indirect evidence of infection. Bacterial and atypical infection correlated with changes in the chest radiograph and high levels of C reactive protein but not with (a) the GP's clinical assessment of whether infection was present, (b) clinical features other than focal chest signs, and (c) outcome, whether or not appropriate antibiotics were prescribed. CONCLUSIONS Over 50% of patients have direct and/or indirect evidence of infection, most commonly bacterial and atypical pathogens, but the outcome is unrelated to the identified pathogens. Many patients improve without antibiotics and investigations do not help in the management of these patients. GPs can reassure patients of the causes and usual outcome of this self-limiting condition.


title: Nosocomial acquisition of methicillin-resistant Staphylococcus aureus during an outbreak of severe acute respiratory syndrome.

text: OBJECTIVE The four hospitals assessed in this study use active surveillance cultures for methicillin-resistant Staphylococcus aureus (MRSA) and contact precautions for MRSA-positive patients as part of routine infection control practices. The objective of this study was to determine whether nosocomial acquisition of MRSA decreased in these hospitals during an outbreak of severe acute respiratory syndrome (SARS) when barrier precautions were routinely used for all patients. DESIGN Retrospective cohort study. SETTING Three tertiary-care hospitals (a 1100-bed hospital; a 500-bed hospital; and an 823-bed hospital) and a 430-bed community hospital, each located in Toronto, Ontario, Canada. PATIENTS All admitted patients were included. RESULTS The nosocomial rate of MRSA in all four hospitals combined during the SARS outbreak (3.7 per 10,000 patient-days) was not significantly different from that before (4.7 per 10,000 patient-days) or after (3.4 per 10,000 patient-days) the outbreak (P = .30 and P = .76, respectively). The nosocomial rate of MRSA after the outbreak was significantly lower than that before the outbreak (P = .003). Inappropriate reuse of gloves and gowns and failure to wash hands between patients on non-SARS wards were observed during the outbreak. Increased attention was paid to infection control education following the outbreak. CONCLUSIONS Inappropriate reuse of gloves and gowns and failure to wash hands between patients may have contributed to transmission of MRSA during the SARS outbreak. Attention should be paid to training healthcare workers regarding the appropriate use of precautions as a means to protect themselves and patients.


title: In vitro and in vivo expression of foreign genes by transmissible gastroenteritis coronavirus-derived minigenomes.

text: A helper-dependent expression system based on transmissible gastroenteritis coronavirus (TGEV) has been developed using a minigenome of 3.9 kb (M39). Expression of the reporter gene beta-glucuronidase (GUS) (2-8 microg per 10(6) cells) and the porcine respiratory and reproductive syndrome virus (PRRSV) ORF5 (1-2 microg per 10(6) cells) has been shown using a TGEV-derived minigenome. GUS expression levels increased about eightfold with the m.o.i. and were maintained for more than eight passages in cell culture. Nevertheless, instability of the GUS and ORF5 subgenomic mRNAs was observed from passages five and four, respectively. About a quarter of the cells in culture expressing the helper virus also produced the reporter gene as determined by studying GUS mRNA production by in situ hybridization or immunodetection to visualize the protein synthesized. Expression of GUS was detected in the lungs, but not in the gut, of swine immunized with the virus vector. Around a quarter of lung cells showing replication of the helper virus were also positive for the reporter gene. Interestingly, strong humoral immune responses to both GUS and PRRSV ORF5 were induced in swine with this virus vector. The large cloning capacity and the tissue specificity of the TGEV-derived minigenomes suggest that these virus vectors are very promising for vaccine development.


Infection control in mass-casualty respiratory care: research needs and future directions.


title: [Novel Research Progress of the Recombinant Vaccine for MERS-CoV].

text: Respiratory syndrome coronavirus in the Middle East (MERS-Co V) has caused wide attention since it was discovered, and the design of effective vaccines for MERS-Co V becomes a hot area at present. Therefore, this review is aimed at novel research progress of the recombinant vaccine for MERS-Co V, including selection and improvement of animal model for vaccine test,construction and optimization of recombinant subunit vaccine, attempts at recombinant live vector vaccine based on varies of vectors, as well as the advantages of pseudovirus. In conclusion, we make a summary about the novel research progress of the recombinant vaccine for MERS-Co V and a promising prospect of its development in terms of both safety and effectiveness verification in the future will be demonstrated.


title: How social structures, space, and behaviors shape the spread of infectious diseases using chikungunya as a case study.

text: Whether an individual becomes infected in an infectious disease outbreak depends on many interconnected risk factors, which may relate to characteristics of the individual (e.g., age, sex), his or her close relatives (e.g., household members), or the wider community. Studies monitoring individuals in households or schools have helped elucidate the determinants of transmission in small social structures due to advances in statistical modeling; but such an approach has so far largely failed to consider individuals in the wider context they live in. Here, we used an outbreak of chikungunya in a rural community in Bangladesh as a case study to obtain a more comprehensive characterization of risk factors in disease spread. We developed Bayesian data augmentation approaches to account for uncertainty in the source of infection, recall uncertainty, and unobserved infection dates. We found that the probability of chikungunya transmission was 12% [95% credible interval (CI): 8-17%] between household members but dropped to 0.3% for those living 50 m away (95% CI: 0.2-0.5%). Overall, the mean transmission distance was 95 m (95% CI: 77-113 m). Females were 1.5 times more likely to become infected than males (95% CI: 1.2-1.8), which was virtually identical to the relative risk of being at home estimated from an independent human movement study in the country. Reported daily use of antimosquito coils had no detectable impact on transmission. This study shows how the complex interplay between the characteristics of an individual and his or her close and wider environment contributes to the shaping of infectious disease epidemics.


title: Acute respiratory distress syndrome.

text: Acute respiratory distress syndrome is the clinical manifestation of severe, acute lung injury. It is characterized by the acute onset of diffuse, bilateral pulmonary infiltrates secondary to noncardiogenic pulmonary edema, refractory hypoxia, and decreased lung compliance. Acute respiratory distress syndrome occurs most frequently in the setting of sepsis, aspiration of gastric contents, trauma, or multiple transfusions. Its complex pathophysiology involves an inciting local or systemic event that initiates pulmonary endothelial and epithelial damage and subsequent increased permeability. Tachypnea, hypoxia, and respiratory alkalosis are typical early clinical manifestations, and they are usually followed by the appearance of diffuse pulmonary infiltrates and respiratory failure within 48 hours. Early identification and treatment of the underlying disorder, along with aggressive supportive care, are essential. Experimental therapies, including those using nitric oxide and surfactant, have not been shown to improve mortality in patients with ARDS, but new therapeutic approaches such as low-volume ventilation have been shown to decrease mortality. Many patients who survive ARDS have permanent, mild to moderate impairment of lung function. Quality of life after hospitalization with ARDS may be poorer than that in similar patients without ARDS.


title: Infrared thermography to mass-screen suspected SARS patients with fever.

text: Fever greater than 38 degrees C is a cardinal sign of patients with the severe acute respiratory syndromes (SARS). To reduce the risk of nosocomial cross infections, screening all patients and visitors who visit hospitals and clinics for fever at the entrance of every hospital building has become a standard protocol in Taiwan during the SARS epidemic from mid-April to mid-June 2003. We used a digital infrared thermal imaging (DITI) system (Telesis Spectrum 9000 MB) to conduct mass screening of patients and visitors who entered the hospital to identify those with fever. The DITI system has two components: a sensor head and a PC imaging workstation. The sensor head is an optic-mechanical device which consists of imagining optics for focusing the infrared source information on the infrared detector. The infrared images are further converted into electrical signals, which are then processed for real-time display on the monitor. During the period from April 13 to May 12 2003, 72,327 outpatients and visitors entered Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan. A total of 305 febrile patients (0.42%) was detected by infrared thermography. Among them, three probable SARS patients were identified after thorough studies including contact history, laboratory tests and radiology examinations. The findings suggests that infrared thermography was an effective and reliable tool ideal for mass-screening patients with fever in the initial phase of screening for SARS patients at a busy hospital which sees approximately 3,000 outpatients every weekday during the SARS epidemic.


Public health in Canada: what are the real issues?


title: PARENTS' AND HEALTHCARE PROVIDERS PERSPECTIVES ABOUT HOSPITALISED CHILDREN BEING VISITED BY OTHER CHILDREN IN NAIROBI, KENYA.

text: BACKGROUND Throughout history, visitation of the hospitalised child has always been restricted. The subject of whether hospitalised children should be visited by other children has been accorded minimal attention. OBJECTIVE To determine the current status of visitation of the hospitalised children and the parents and healthcare providers'views on hospitalised children being visited by other children. DESIGN A descriptive study carried out using quantitative and qualitative methods in two phases SETTING All paediatric wards at Kenyatta National Hospital and Gertrudes Children's Hospital. SUBJECTS Nurses, paediatricians and parents of hospitalised children. RESULTS A total of 161 parents participated in phase I of the study whereas 11 nurses not specialised in paediatric nursing, 13 paediatric nurses, 12 nurse managers, fur paediatricians and13 parents participated in phase II of the study. The study established that visiting of the hospitalised child by family members especially children aged below twelve years is severely restricted particularly in the public hospital. Despite this, however, majority of the healthcare providers and the parents acknowledged the importance of the hospitalised children being visited by other children. This is because it promotes healing, gives the sick child psychological satisfaction and relieves anxiety in the hospitalised child, the accompanying parent and the other children. The risk of exposing the visiting children to infection was cited as the main reason for the restrictions. CONCLUSION Both the healthcare providers and the hospitalised children's parents appreciate the importance of the hospitalised child being visited by other children. There is a need to review healthcare policies to make provision for hospitalised children to be visited by other children.


title: Intra-corporeal anastomosis in laparoscopic surgery for benign colorectal disease.

text: INTRODUCTION Recent studies have described the benefits of performing bowel resections for benign and malignant diseases as a total laparoscopic procedure with intra-corporeal anastomosis. We describe our preliminary experience with total laparoscopic surgery for benign lower gastrointestinal diseases. METHODS All patients (n = 32) who had received elective bowel surgery with intra-corporeal anastomosis for benign diseases between November 2013 and August 2015 were included in this retrospective study. RESULTS A total of 15 patients (47%) had a primary anastomosis, 17 patients (53%) had a stoma reversal. The median length of stay was five days (range: 3-16). Surgical complications requiring re-operation were present in five patients (Clavien-Dindo grade IIIb) of whom two presented with anastomotic leaks (6%; 95% confidence interval: 2-20%). No post-operative medical complications according to the Clavien-Dindo Classification were seen. The median duration of surgery was 127 min. (range: 61-211 min.). No deaths occurred. CONCLUSION A total laparoscopic approach to benign lower gastrointestinal diseases with intra-corporeal ana-stomosis was feasible. FUNDING none. TRIAL REGISTRATION The trial is registered with the Danish Data Protection Agency.


title: The urban geography of SARS: paradoxes and dilemmas in Toronto's health care.

text: BACKGROUND Severe acute respiratory syndrome (SARS) has impacted heavily on both Canada's society and its health care system. Quite unexpectedly, hospitals and health care workers became facilitators of disease diffusion. This experience has demonstrated the need for a comprehensive disease control strategy. AIMS The aims are threefold. First, to examine the subtle and changing spatial characteristics of SARS during the short but critical period of its rapid spread in the Greater Toronto Area. Second, to make salient three paradoxes, and their associated dilemmas, faced by nurses and other health care professionals challenged with caring for the sick and containing the rapid spread of the disease. Third, to propose some ways of approaching these dilemmas, as well as some broader preventative and mitigating strategies. METHODS The crosscutting concepts of 'clinical uncertainty' and 'flow of human contacts' are used to explain disease transmission characteristics and urban spatial diffusion and to guide the particular strategies developed. Evidence for the paper comes from public health records, governmental and non-governmental health statements and the initial epidemiological research on SARS. Direct insights are also gained from recent first-hand experiences of Toronto's health care system during the crisis. DISCUSSION The concepts of clinical uncertainty and the flow of human contacts provide in-depth insights that complement the findings of large-scale epidemiological studies, and help operationalize their general calls for enhanced control measures. The comprehensive disease control strategy proposed includes the creation of a hospital infrastructure specific to the containment of biological threats; an advisory coalition of disease control specialists; the development of a biological threat-and-containment simulation laboratory and three specific programmes in patient safety, risk assessment and community mobilization. CONCLUSION It is argued that containment alone, while a necessary and urgent priority, cannot be seen as an end in itself and might better be understood as one possible trajectory within a comprehensive problem-solving strategy. The experiences in Toronto may offer insights to other cities and countries that currently lack such strategies and hence may be vulnerable to similar outbreaks of dangerous infectious diseases.


Human metapneumovirus: a not so new virus.


title: [Change of T lymphocyte and its activated subsets in SARS patients].

text: OBJECTIVE To study abnormal changes of T lymphocyte and its activated subsets in severe acute respiratory syndrome (SARS) patients. METHODS Flow cytometer with multi-color flouroscence and hematology analyzer were used to detect the expression of T lymphocyte and its activated a subsets in 240 SARS patients including 50 cases of critical type and 190 cases of common type. RESULTS Statistical analysis by means of SAS software showed that there was significant decrease in absolute counts (AC) of T lymphocyte and its subsets in SARS patients when compared with normal people, while percentages (PC) of CD3+CD25+ and CD3+ HLA-DR+ subsets were increased markedly. Compared with common type, there was significant decrease in absolute counts of critical type of T lymphocyte, CD4+, CD25+CD3+, CD28+CD4+, and CD95+CD4+subsets. The ACs of T lymphocytes including CD4 and CD8 subsets in different phases were as below: III > II > I. The ACs of subsets involved in activation such as CD3+ HLA-DR+/lym, CD3+CD25+/lym, CD28+CD4+/CD4, CD28+CD8+/CD8, and CD38+CD4+/CD4 all were highest in group III. In addition, the AC and PC of CD95+CD4+/CD4 and CD95+CD8/CD8 subset in group III were highest while group I was lowest. CONCLUSIONS With depressing cellular immunity, the activation of T lymphocytes were suppressed obviously in SARS patients, especially for critical patients.


title: Viral hyperinfection of the central nervous system and high mortality after hematopoietic stem cell transplantation for treatment of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

text: Theiler's murine encephalomyelitis virus (TMEV) establishes a persistent infection in the central nervous system (CNS) leading to an inflammatory demyelinating disease of the CNS in which the histology and clinical course is similar to multiple sclerosis (MS). Disease pathogenesis is primarily due to T-cell-mediated destruction of myelin, which has been attributed to cytopathic effects of the virus, but immune-mediated destruction of myelin mediated via both virus-specific and myelin-specific T cells appear to play the major role. To determine if bone marrow transplantation would be an effective therapy for a virus-initiated autoimmune disease and to better separate viral cytopathic effects from immune-mediated demyelination, we ablated the immune system of TMEV-infected animals with 1,100 cGy total body irradiation, and then the animal's immunity was reconstituted by transplantation of disease-susceptible SJL/J mice with syngeneic marrow or disease-susceptible DBA/2J with marrow from disease-resistant (C57Bl/6 x DBA/2)F1 (B6D2) donors. Hematopoietic transplant performed after onset of disease resulted in 42% mortality in SJL/J syngeneic transplants, 47% mortality in diseased DBA2 recipients restored with marrow from naive B6D2 donors, and 12% in diseased DBA2 recipients receiving marrow from B6D2 donors previously infected with TMEV. Delayed type hypersensitivity (DTH) to both virion and myelin proteins was decreased in surviving mice that underwent transplantation; however, CNS viral titers were significantly elevated compared with nontransplanted controls. We conclude that a functional immune system with appropriate T-cell responses are important in prevention of lethal cytopathic CNS effects from TMEV. Relevant to the clinical use of bone marrow transplantation, attempts to ablate the immune system in viral-mediated immune diseases or virus-initiated autoimmune disease may have acute and lethal consequences. Our results raise concern about the attempted use of autologous hematopoietic transplantation in patients with MS, an autoimmune disease with a suspected virus etiology, particularly if the graft is aggressively depleted of lymphocytes.


Globalization and the health of the health care workforce.


title: [Kawasaki disease].

text: Kawasaki disease is a systemic acute vasculitis of unknown etiology. It is the leading cause of acquired heart disease in children in the USA. It occurs more frequently in boys and eighty percent of the cases occur in children under five years of age. The disease rarely occurs after eight years and it can affect children of all races, with higher incidence among Asian descendants. Kawasaki disease is characterized by fever, bilateral non-exudative conjunctivitis, redness and swelling of the tongue, lips and oral mucosa, abnormalities in the extremities, cervical lymph node, and polymorphic exanthema. Aneurysms and stenoses of coronary arteries occur in approximately 20 to 25% of untreated patients and subsequently can lead to acute myocardial infarction and sudden death. Treatment with intravenous immunoglobulin is effective and should be initiated early to prevent cardiac sequel. The development of diagnostic tests, more specific treatment approaches and prevention of this potentially fatal disease in children depends on continuous advances in the determination of its pathogenesis.


title: The Tecumseh study of respiratory illness. VIII. Acute infection in chronic respiratory disease and comparison groups.

text: Individuals with chronic lung disease and their families were selected from the Tecumsch community along with similarly selected families as comparison groups and studied for 1-year periods. Occurence of acute respiratory illness was ascertained weekly by telephone and calculated as an annual rate. Persons with chronic bronchitis not only experienced more acute lower respiratory illness than healthy comparison subjects, but total illness rates were somewhat higher as well. Infection rates were determined from blood samples taken 3 times from each participant during the surveillance year. Antibody tests were performed for respiratory syncytial virus, para-influenza virus types 1, 2, and 3, influenza types A and B, coronavirus OC43, Mycoplasma pneumoniae, and Haemophilus influenzae. Differences in serologic infection rates among the subgroups of the population were similar to those seen in the clinical data, with more frequent infection among those with bronchitis than among the comparison subjects. This finding indicates that some degree of increased susceptibility to actual infection existed among those individuals with bronchitis. Influence of smoking on illness and infection rates was also examined. Infections were, in general, more frequent in smokers than in nonsmokers, but illness rates were reversed, suggesting that perception of disease differed in the 2 groups. Rates of illness and infection of other adults in the families of the index individuals with bronchitis were not influenced by the higher rates seen in the index individuals; however, it was of interest that children of persons with bronchitis did have somewhat higher rates of infection than children of comparison subjects.


title: Comparative analysis of Coronaviridae nucleocapsid and surface glycoprotein sequences.

text: We analyzed the nucleocapsid and surface proteins from several Coronaviridae viruses using an alignment-free computer program. Three isolates of novel, human coronavirus (SARS0CoV-2) (2019) that are responsible for the current pandemic and older SARS strains of human and animal coronaviruses were examined. The nucleocapsid and glycoprotein sequences are identical for the three novel 2019 human isolates and they are closely related to these sequences in six bat and human SARS coronaviruses. This strongly supports the bat origin of the pandemic, novel coronavirus. One surface glycoprotein fragment of 111 amino acids is the largest, conserved, common permutation in the examined bat SARS-like and human SARS viruses, including the Covid-19 virus. BLAST analysis confirmed that this fragment is conserved only in the human and bat SARS strains. This fragment likely is involved in infectivity and is of interest for vaccine development. Surface glycoprotein and nucleocapsid protein sequence homologies of 58.9% and 82.5%, respectively, between the novel SARS0CoV-2 strains and the human SARS (2018) virus suggest that existing anti-SARS vaccines may provide some protection against the novel coronavirus.


Correlation between MRI, computed tomographic findings and clinical signs in a case of ovine coenurosis.


title: Detection of feline coronavirus in captive Felidae in the USA.

text: Feline coronavirus (FCoV) is an important pathogen of domestic and nondomestic Felidae. Investigation into the prevalence of FCoV in exotic Felidae has relied primarily on serology. The usefulness of genetic detection of FCoV using reverse transcription and nested polymerase chain reaction (RT/nPCR) for viral screening was investigated. Seventy-five biologic samples, primarily feces, from captive felids from 11 institutions were tested using PCR. Serum samples collected from all but 12 of these animals were tested for antibodies to type I and type II FCoV by indirect immunofluorescence. Twenty-four animals were positive using RT/nPCR for virus. Twenty-nine animals were seropositive to type I and/or type II FCoV. From serologic data, infection with a virus antigenically related to FCoV type I occurred most commonly. Serology did not correlate with virus shedding because 13 animals were seronegative to FCoV type I and II but positive using RT/nPCR for virus. Conversely, 20 animals were seropositive but negative using RT/nPCR for FCoV. Some of the populations in which virus was detected had experienced health problems, including feline infectious peritonitis (FIP), necrotizing colitis, and mild enteritis. In addition to its role in FIP, this virus may play a role in gastrointestinal diseases of infected animals. This study demonstrates that FCoV is a significant infectious agent of captive felids because over half of the animals tested were positive by viral genetic detection, serology, or both. Dependence upon one method for detection of infection is unreliable.


title: [Asymptomatic SARS-CoV-2 infection in children: a clinical analysis of 20 cases].

text: OBJECTIVE To study the clinical and epidemiological features of children with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS The clinical data of 20 children who were diagnosed with asymptomatic SARS-CoV-2 infection from January 20 to March 4, 2020 were analyzed. RESULTS Among the 20 children, there were 7 boys (35%) and 13 girls (65%), aged 8 months to 14 years (mean 8±5 years). All these children had no clinical manifestations and attended the hospital for an epidemiological history of SARS-CoV-2. Nineteen children were shown with family aggregation of SARS-CoV-2 infection. Nasopharyngeal swabs were PCR-positive for SARS-CoV-2 in all 20 children. There were 4 children (20%) of mild type, 16 children (80%) of common type, and no children of severe type or critical type. The mean peripheral blood leukocyte count was (6.8±3.5)×109/L, and 7 children had an abnormal peripheral blood leukocyte count, with an increase in 5 children and a reduction in 2 children. One child had a decreased absolute value of lymphocytes (0.87×109/L), 3 children had an increased erythrocyte sedimentation rate (20-42 mm/h), 7 children had an increased lactate dehydrogenase level (>400 U/L), and 4 children had an increased blood lactate level (>1.6 mmol/L). Chest CT showed single or multiple small nodule shadows, patchy shadows, and ground-glass shadows in the middle or lateral lobe of lungs or under the pleura in 13 children. CONCLUSIONS Pediatric cases of asymptomatic SARS-CoV-2 infection mostly occur with family aggregation. Most of the children with asymptomatic infection have no obvious abnormalities in blood routine and other laboratory tests. Changes in chest CT scan can be used as an aid for early diagnosis of asymptomatic infection in children.


title: Thyroid activity in patients with major depression.

text: Hypothalamus-pituitary-thyroid (HPT) axis dysfunction has been associated with pathophysiology of major depression. The aim of the study was to determine serum levels of total 3,5,3'-triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating-hormone (TSH) in patients with major depression and healthy controls. The study included 53 medication-free patients with depression and 49 healthy controls. Exclusion criteria for patients was: other axis-I and axis-II diagnoses, intensive psychotherapy or electroconvulsive therapy, prior clinical and/or laboratory evidence of hypo- or hyperthyroidism, alcohol or nicotine dependence, pregnancy, hormone supplement therapy, somatic illnesses (diabetes, renal or hepatic disorders), infections or autoimmune diseases, recent surgical treatment or significantly changed body weight. For controls: the presence of psychiatric disorders and/or thyroid dysfunctions. The diagnosis of major depression was made using structured clinical interview based on DSM-IV criteria. The results showed significantly lower T3 and TSH levels in patients compared to controls. There was no significant difference in T4 values between patients with depression and control subjects. The results showing altered levels of thyroid hormones in depression indicate that further research on thyroid hormone activity can contribute to the better understanding of the biological basis of depression. Based on the high frequency of the subtle neuroendocrine disorders coexisting with depression, the association of thyroid abnormalities and depression should not be underestimated. Future research should identify different behavioral endophenotypes characteristic for depression, which would greatly facilitate delineating the biological phenomena associated with this psychiatric illness.


title: [Management of gastrointestinal and hepatic diseases during the COVID-19 outbreak].

text: The current epidemic of SARS-CoV-2 infection poses new challenges in the management of patients with gastrointestinal or liver disease. Consultations with patients with chronic diseases should ideally be done via telemedicine and treatments administered at home if possible. The latter should be maintained in non-infected subjects to limit the risk of decompensation of their underlying disease. In the event of proven infection, immunomodulatory or biological treatments will tend to be reduced or discontinued unless the disease is in a severely active phase. Elective endoscopy should be postponed, and urgent procedures should be performed with appropriate personal protective equipment.


title: Local and systemic cell-mediated immunity against transmissible gastroenteritis, an intestinal viral infection of swine.

text: The occurrence of local and systemic cell-mediated immunity (CMI) in swine against transmissible gastroenteritis (TGE) virus, a coronavirus that infects the epithelial cells of the small intestine of swine, has been investigated. Leukocyte suspensions prepared from intestinal lamina propria (LP) and spleen were each incubated with and without inactivated TGE virus. The supernatants from these cultures were tested for the presence of macrophage migration inhibition factor (MIF) by the indirect MIF test using guinea pig peritoneal exudate cells as the source of macrophages. All swine serologically negative for TGE antibodies (i.e., unexposed to TGE virus) were also negative for MIF production by lymphocytes from both sources. In 10 of 10 animals given TGE virus subcutaneously, MIF production by splenic lymphocytes was significantly greater (p less than or equal to 0.01) than by LP lymphocytes, and in 9 of 10 of these animals MIF production by LP lymphocytes was negligible (percentage of inhibition of migration less than 3%).


title: The immunological synapse for B-cell memory: the role of the ICOS and its ligand for the longevity of humoral immunity.

text: RECENT FINDINGS The ICOS is one of the many costimulatory molecules of T cells. Recently, the authors discovered that the homozygous loss of the ICOS in humans presents as common variable immunodeficiency, the most prevalent treated primary immunodeficiency in man. Therefore, the ICOS is after CD40 and CD40-ligand deficiency the third costimulatory molecule for which a human disease has been described. PURPOSE OF REVIEW The description of ICOS deficiency made it necessary to review the vast amount of knowledge from experimental models in the light of a new clinical immunodeficiency phenotype. To this end, after introducing the ICOS and its ligand and comparing the murine and human 'knockout', the role of the ICOS in parasitic and viral infections, asthma, autoimmunity, transplantation immunology, and tumor surveillance will be discussed. SUMMARY The focus of this review is the interaction between the ICOS and its ligand, which is essential for T cell dependent B cell responses.


title: A leader sequence is present on mRNA A of avian infectious bronchitis virus.

text: The subgenomic mRNAs of the fowl coronavirus infectious bronchitis virus (IBV) form a 3' co-terminal or 'nested' set. The RNase T1 oligonucleotide mapping data which demonstrated this form of sequence organization provided no evidence for the presence of non-contiguous (leader) sequences fused to the 5' termini of the mRNAs. However, we have been able to demonstrate, by extension of an end-labelled synthetic oligonucleotide primer, the presence of a leader sequence on IBV mRNA A. Sequencing by the chemical degradation method of the extended product has yielded the almost complete sequence of the 60 base leader and its point of fusion to the sequence of the virus genomic RNA.


title: Influenza surveillance in Indonesia: 1999-2003.

text: Although influenza is recognized for its worldwide importance, little is known about the disease from tropical countries like Indonesia. From August 1999 through January 2003, a surveillance study was conducted in clinics at 6 sentinel locations. Adults (age, >14 years) and children (age, 4-14 years) presenting with respiratory symptoms suggestive of influenza were asked to enroll in the study. Nasal and pharyngeal swabs were examined by virus isolation, polymerase chain reaction, and rapid immunochromatographic tests. A total of 3079 specimens were collected from 1544 participants. Influenza infection was confirmed in 172 volunteers (11.1%) presenting with influenza-like illness. Influenza A (H1N1 and H3N2) and B viruses were detected at all sites. Peak prevalence tended to coincide with the respective rainy seasons, regardless of location. In light of the recent epidemic of severe acute respiratory syndrome, continued influenza surveillance would be useful in strengthening the infrastructure of the Indonesian public health system.


title: High-throughput, sensitive, and accurate multiplex PCR-microsphere flow cytometry system for large-scale comprehensive detection of respiratory viruses.

text: Human respiratory viruses are a diverse group of pathogens composed of hundreds of virus strains, and this presents a major challenge for diagnostic laboratories. To efficiently detect numerous viruses in a large epidemiologic study, we developed a fast, multitarget, sensitive, and specific assay named the Respiratory MultiCode-PLx Assay (RMA). The RMA utilizes improved multiplex PCR chemistry (EraGen MultiCode-PLx technology) coupled with high-throughput microsphere flow cytometry (Luminex). Eighteen sets of virus-specific multiplex PCR primers were developed based on the conserved sequences of all available respiratory-virus sequences for eight distinct groups: human rhinovirus (HRV), respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza virus (InfV), metapneumovirus, adenovirus (Ad), coronavirus, and enterovirus. Each primer set detected 20 cDNA copies of the intended target per sample and had no reaction with 60,000 copies of human genomic DNA. The accuracy and sensitivity of the RMA for detecting respiratory viruses in human samples were tested with two sets of clinical specimens. First, 101 nasal-wash specimens that were positive for HRV, RSV, InfV, PIV, or Ad by traditional techniques were reanalyzed by RMA, and all target viruses were detected with an overall sensitivity of 94% and specificity of 99%. Second, 103 nasal-wash samples from 5-year-old children with asthma and respiratory symptoms were analyzed; RMA detected viruses in 74 specimens (71.8%) compared to only 24 (23.3%) by traditional culture and immunofluorescent-staining techniques. These results show that RMA is an accurate, sensitive, and practical test for respiratory-virus infections.


title: Coronavirus minus-strand RNA synthesis and effect of cycloheximide on coronavirus RNA synthesis.

text: The temporal sequence of coronavirus plus-strand and minus-strand RNA synthesis was determined in 17CL1 cells infected with the A59 strain of mouse hepatitis virus (MHV). MHV-induced fusion was prevented by keeping the pH of the medium below pH 6.8. This had no effect on the MHV replication cycle, but gave 5- to 10-fold-greater titers of infectious virus and delayed the detachment of cells from the monolayer which permitted viral RNA synthesis to be studied conveniently until at least 10 h postinfection. Seven species of poly(A)-containing viral RNAs were synthesized at early and late times after infection, in nonequal but constant ratios. MHV minus-strand RNA synthesis was first detected at about 3 h after infection and was found exclusively in the viral replicative intermediates and was not detected in 60S single-stranded form in infected cells. Early in the replication cycle, from 45 to 65% of the [3H]uridine pulse-labeled RF core of purified MHV replicative intermediates was in minus-strand RNA. The rate of minus-strand synthesis peaked at 5 to 6 h postinfection and then declined to about 20% of the maximum rate. The addition of cycloheximide before 3 h postinfection prevented viral RNA synthesis, whereas the addition of cycloheximide after viral RNA synthesis had begun resulted in the inhibition of viral RNA synthesis. The synthesis of both genome and subgenomic mRNAs and of viral minus strands required continued protein synthesis, and minus-strand RNA synthesis was three- to fourfold more sensitive to inhibition by cycloheximide than was plus-strand synthesis.


title: [Analysis of severe acute respiratory syndrome in Beijing].

text: OBJECTIVE To study the clinical, laboratory, and radiologic features of 34 cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS All patients were admitted to the isolation wards. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Univariate and multivariate analyses were performed. RESULTS Eight patients came from a family, and 15 patients were medical staff. The mean age of patients was (33.4 +/- 13.4) years. The latent period varied from 2 to 14 days (median 4 days). The most common symptoms were fever (100%), palpitation (91.7%), myalgia (79.2%), headache (70.8%), diarrhea (73.9%) and cough (58.3%). The mean leucocyte count was (4.6 +/- 1.4) x 10(9)/L, and the mean lymphocyte ratio was 0.27 +/- 0.11. 68.4% of the patients had lymphopenia (absolute lymphocyte count < 1.3 x 10(9)/L). Other common findings included elevated levels of serum alanine aminotransferase, lactate dehydrogenase and erythrocyte sedimentation (76.2%, 28.6% and 47.8%, respectively), and decreased levels of serum iron and albumin (63.2% and 47.8%, respectively). Thirty-two cases had abnormal chest radiographs. In 2 cases in whom typical lung opacities could not be found on the initial plain chest radiographs, thoracic CT proved to be useful. Postmortem examination of 1 patient revealed marked edema with foci of hemorrhage and hyaline membrane formation in the lungs, hemorrhage necrosis and a obvious decline of cells in lymph glands. In a multivariate analysis (Stata 7.0), the independent predictor of an adverse outcome was advanced age (odds ratio per decade of life, 1.6; 95% CI, 1.08 to 2.63; P = 0.007). CONCLUSIONS Fever, lymphopenia, low serum iron and chest radiograph are helpful to diagnose SARS early; age is the independent predictor of an outcome.


title: [Porcine aminopeptidase N is a functional receptor for the PEDV coronavirus].

text: Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in piglets that leads to great economic losses in East Asia. It was reported that aminopeptidase N (APN) was the receptor for Transmissible gastroenteritis virus (TGEV), Human coronavirus 229E (HCoV-229E) and Feline coronavirus (FeCoV) which all belonged to group I coronavirus including PEDV. It was also confirmed previously that porcine aminopeptidase N (pAPN) could bind to PEDV, and anti-pAPN antibodies could inhibit the combination. To investigate whether pAPN was a receptor for PEDV, we transfected MDCK cells with porcine aminopeptidase (pAPN) cDNA and this enabled non-susceptible cells to support PEDV replication and serial viral propagation. Moreover, the infection was blocked by antibodies against pAPN, implying the critical role of pAPN during virus entry. In addition, immunofluorescence assays for detection of pAPN and PEDV antigens, together with neutralization assays using antibodies against pAPN, further confirmed the correlation between pAPN expression and viral replication in pAPN-transfected MDCK cells. These results indicated that pAPN is a functional receptor for PEDV.


title: Synthesis and processing of the bovine enteric coronavirus haemagglutinin protein.

text: The haemagglutinin molecule on the bovine enteric coronavirus has been identified as a glycoprotein of 140K composed of disulphide-linked subunits of 65K. In this study, we have shown the subunits to be identical by demonstrating an unambiguous amino-terminal amino acid sequence. The unglycosylated subunit was found to have an Mr of 42.5K and to undergo rapid disulphide linkage and glycosylation. Glycosylation was found to be of the asparagine-linked type and some of the oligosaccharides underwent processing to complex forms. Studies with inhibitors of glycosylation suggested that a processing of the haemagglutinin oligosaccharide takes place on the virion whilst it is in the Golgi apparatus. Each haemagglutinin subunit on the mature virion was estimated to possess six or seven carbohydrate chains of either the high-mannose or hybrid type, and three or four chains of the complex type.


Physical interaction between the membrane (M) and envelope (E) proteins of the coronavirus avian infectious bronchitis virus (IBV).


title: Naturally occurring anti-Escherichia coli protein antibodies in the sera of healthy humans cause analytical interference in a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay for serodiagnosis of severe acute respiratory syndrome.

text: We reported the analytical interference of anti-Escherichia coli protein (EP) antibodies in human sera and residual EP in a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay as a possible source of false positives in severe acute respiratory syndrome serodiagnosis. The rate of false positives was significantly reduced by adding mouse anti-EP antiserum in the blocking step.


title: The viral nucleocapsid protein of transmissible gastroenteritis coronavirus (TGEV) is cleaved by caspase-6 and -7 during TGEV-induced apoptosis.

text: The transmissible gastroenteritis coronavirus (TGEV), like many other viruses, exerts much of its cytopathic effect through the induction of apoptosis of its host cell. Apoptosis is coordinated by a family of cysteine proteases, called caspases, that are activated during apoptosis and participate in dismantling the cell by cleaving key structural and regulatory proteins. We have explored the caspase activation events that are initiated upon infection of the human rectal tumor cell line HRT18 with TGEV. We show that TGEV infection results in the activation of caspase-3, -6, -7, -8, and -9 and cleavage of the caspase substrates eIF4GI, gelsolin, and alpha-fodrin. Surprisingly, the TGEV nucleoprotein (N) underwent proteolysis in parallel with the activation of caspases within the host cell. Cleavage of the N protein was inhibited by cell-permeative caspase inhibitors, suggesting that this viral structural protein is a target for host cell caspases. We show that the TGEV nucleoprotein is a substrate for both caspase-6 and -7, and using site-directed mutagenesis, we have mapped the cleavage site to VVPD(359) downward arrow. These data demonstrate that viral proteins can be targeted for destruction by the host cell death machinery.


title: The pathogenesis of MHV nucleocapsid gene chimeric viruses.

text: A set of viruses in which various segments of the nucleocapsid (N) gene of MHV have been substituted with the corresponding segments of bovine coronavirus (BCV) by targeted recombination were analyzed for their biologic properties. Histology for organ pathology and plaque assay for viral titer analysis following intracerebral (IC) inoculation were studied. One chimeric virus (Alb85), in which only a small segment of the N gene was replaced, exhibited a phenotype similar to wild type MHV-A59. However, three of the chimeric viruses (Alb106, Alb112 and Alb100) produced acute encephalitis and demyelination but without hepatitis following IC inoculation. Intravenous (IV) and intrahepatic (IH) inoculations were able to restore the ability of these viruses to produce hepatitis. The common denominator of the three chimeric viruses with a different phenotype is a region between aa 306 and aa 386 in which 17 amino acids (aa) differences exist between the two strains. Thus this region may contain determinants which enable the virus to exit the brain and reach the blood stream.


title: Expression and functional characterisation of the putative SARS coronavirus non-structural proteins X1-X5.

text: 1. We produced mammalian expression vectors encoding the SARS coronavirus (SARS-CoV) accessory proteins with or without the fluorescence protein tag and cell lines with stable expression of these proteins. 2. The cellular localisation and function of the SARS-CoV accessory proteins was determined. 3. SARS 6 and SARS 8b proteins are localised to the endoplasmic reticulum and nucleus/cytoplasm, respectively, and both proteins stimulate host cell DNA synthesis.


title: The psychological effect of severe acute respiratory syndrome on emergency department staff.

text: BACKGROUND The severe acute respiratory syndrome (SARS) outbreak in 2003 affected 29 countries. The SARS outbreak was unique in its rapid transmission and it resulted in heavy stress in first-line healthcare workers, particularly in the emergency department. AIM : To determine the influence of SARS on the psychological status, including post-traumatic stress disorder (PTSD) symptoms, of the staff in the emergency department. METHODS To investigate whether different working conditions in the hospital led to different psychological effects on healthcare workers, the psychological effect on emergency department staff in the high-risk ward was compared with that on psychiatric ward staff in the medium-risk ward. Davidson Trauma Scale-Chinese version (DTS-C) and Chinese Health Questionnaire-12 (CHQ-12) items were designed to check the psychological status of the staff in the month after the end of the SARS outbreak. RESULTS 86 of 92 (93.5%) medical staff considered the SARS outbreak to be a traumatic experience. The DTS-C scores of staff in the emergency department and in the psychiatric ward were significantly different (p = 0.04). No significant difference in CHQ score was observed between the two groups. Emergency department staff had more severe PTSD symptoms than staff in the psychiatric ward. CONCLUSION SARS was a traumatic experience for healthcare providers in Taiwan. Most staff in the emergency department and in the psychiatric ward had PTSD. Emergency department staff had more severe PTSD symptoms than staff in the psychiatric ward.


title: Intra-articular versus serum C-reactive protein analysis in suspected periprosthetic knee joint infection.

text: The purpose of this study was to investigate the comparative diagnostic strength of C-reactive protein (CRP) values in synovial fluid and serum in patients with presumed periprosthetic joint infection. We collected 44 synovial fluid samples and 24 serum samples from 43 patients. Patients were judged to be uninfected or infected based on standardized criteria. Synovial and serum samples were obtained simultaneously. We determined the diagnostic strength of our assay by using receiver operating characteristic curve analysis, calculated the cutoff value and calculated the difference in diagnostic strength for periprosthetic joint infection between synovial fluid and blood serum analysis. The area under the curve was 0.977 for intra-articular CRP analysis and 0.979 for serum CRP analysis. The cutoff points for intra-articular CRP analysis where 1.8 mg/L and 2.8 mg/L. Both tests showed a very high diagnostic strength; the difference in diagnostic strength between synovial fluid and blood serum analysis was not significant (p = 0.66).


title: Characteristics of porcine circovirus-2 replication in lymphoid organs of pigs inoculated in late gestation or postnatally and possible relation to clinical and pathological outcome of infection.

text: In this study, the characteristics of porcine circovirus-2 (PCV2) replication (infectious virus titrations, distribution, and immunophenotyping of infected cells) in lymphoid organs were examined and related to the development of clinical signs and histological lesions in 26 piglets that had been inoculated with PCV2 either in utero or at 1 day of age. Piglets inoculated in utero at 92 or 104 gestational days (n = 12) were collected by Caesarean section at term and either sacrificed immediately or kept in isolators and allowed to live postnatally until 35 days postinoculation (PI). Caesarean-derived piglets inoculated at 1 day of age (n = 14) were sacrificed at 10, 21, 35, 42, and 49 days PI. Spleen and lymph nodes were collected for virologic and histopathological examinations. Clinical signs were not observed in any of the piglets. High virus titers (10(4.5-5.7) TCID50/g [TCID refers to tissue culture infectious dose]) were detected in 6 of the 26 piglets. Three of these 6 piglets were euthanized at 10 days PI, and infected cells of the monocyte-macrophage lineage (SWC3+, CD14+, and sialoadhesin [Sa]+ cells) and infected cells bearing lymphocyte markers (CD4+, CD8+, and immunoglobulin M+ cells) were identified by double-immunofluorescence labeling on serial cryostat sections. The other 3 piglets were euthanized at 21 and 35 days PI, and the majority of infected cells were SWC3+, CD14+, and Sa-. The absence of Sa in these infected cells, together with their localization in lymphocyte-dependent regions, suggests that they were infiltrating monocytic cells. Sialoadhesin is highly expressed in differentiated macrophages and not in peripheral blood mononuclear cells. In all 6 piglets with high virus titers, lymphocyte depletion and infiltration of monocytic cells were observed. In the remaining 20 piglets with virus titers less than 10(4.5) TCID50/g, the majority of infected cells were SWC3+, CD14+, and Sa+. In conclusion, it can be stated that high PCV2 titers in lymphoid organs may lead to the development of histological lesions similar to those observed in pigs with postweaning multisystemic wasting syndrome without causing disease. Furthermore, in lymphoid organs with high virus titers, infection occurs mainly in infiltrating monocytic cells and to a limited extent in cells bearing lymphocyte markers.


title: Bacterial carriage and respiratory tract infections in subjects > or = 60 years during an influenza season: implications for the epidemiology of community acquired pneumonia and influenza vaccine effectiveness.

text: INTRODUCTION During the 2010/11 influenza season an epidemiological prospective cohort active study was organized, to evaluate etiologic role due to the main bacteria and viruses causing Community Acquired Pneumonia (CAP) and Influenza like-illness (ILl) in elderly and to explore the role of the bacterial nose-pharingeal carriage in subjects with respiratory tract infections. METHODS An integrated active surveillance of a cohort of adults aged > or = 60 y based on a double prospective and retrospective mechanisms of capture of ILl and CAP cases was organized. Samples were collected from all ILI and CAP prospectively identified. The samples were be tested by multiplex PCR for detection of the main respiratory bacteria and viruses. RESULTS AND DISCUSSION The study population amounted to 2,551 adults. During the 2010/11 influenza season, the ILl cumulative incidence was 4.2%, that was twice higher than that calculated by regional sentinel-based Influenza surveillance system during the 2010/11 season in the elderly (2.2%). Among 45 patients with ILI of which had been collected the swab, 17 (37.8%) were positive for influenza viruses and 2 (4.4%) for RSV, 6 (13.3%) patients carried Streptococcus pn and 6 (13.3%) Haemophilus in. In the same period, 7 CAP cases were observed; 3 cases were prospectively identified and samples were collected, while 4 cases were retrospectively detected. The CAP cumulative incidence was 0,3%. The influenza vaccine effectiveness in prevention of laboratory-confirmed influenza emerged by our study was 61%, in condition of good antigenic matching between vaccine and circulating strains observed during the 2010/11. These data contribute to better defining the epidemiological picture of upper and lower respiratory tract infections, fundamental information in light of the recent introduction of new vaccines for prevention of pneumonia in the elderly, including 13-valent conjugate pneumococcal vaccine.


title: Integrating nutrition with ecology: balancing the health of humans and biosphere.

text: OBJECTIVE To show that current rates of global population growth, production and consumption of food, and use of living and physical resources, are evidently not sustainable. To consider ways in which nutrition and allied sciences can respond to this great challenge of the twenty-first century. METHOD Past, current and future projected trends in production and consumption patterns are examined. These show that overall present and projected patterns cannot be sustained; and also show increasing unacceptable inequity between and within rich and poor regions and countries. DISCUSSION Nutrition science classically focuses on nutrients in relation to human physiology, metabolism, growth, health and disease. The social and environmental conditions of the modern, interconnected, market-oriented world, and the consequences for food production and consumption, are extending the research and policy agenda with which nutrition science must now urgently engage. Historically, much attention has been paid to eliminating nutritional deficiency states, and this remains an important task. In modern urban populations 'malnutrition' encompasses new forms of dietary imbalance, especially excesses of certain nutrients. These contribute to various non-communicable diseases and, particularly, to overweight/obesity and its attendant metabolic derangements and disease risks. As a mass phenomenon the current surge in obesity has no historical precedent. The escalating impact of humankind on the natural environment, with its ramifications for present and future food production, is also unprecedented. CONCLUSION The essential challenge for nutrition science is to develop new understanding and strategies to enable a balance between promoting, equitably, the health of humans while sustaining the long-term health of the biosphere. Extension of nutrition science and food policy to meet those goals will be aided by understanding better how dietary conditions shaped the biological evolution of humankind. The fundamental long-term task is to integrate human health with the health of the biosphere.


title: [Effect on mRNA and secretion levels of proinflammatory cytokines in DC infected by SARS-CoV N gene recombinant adenovirus].

text: OBJECTIVE To investigate the exact mechanism of SARS-CoV pathogenesis at the protein level. METHOD Under the condition of the establishment of dendrtic cells (DC) culture method, we used recombinant adenovirus to infect mature DC to make clear the development changes in mRNA levels and secreted protein levels of proinflammatory cytokines of IL-1beta, IL-6, IL-8 and TNF-alpha by using RT-PCR and ELISA. RESULT We found that mRNA levels and secreted protein levels of IL-6 and TNF-alpha in DC had increased gradually after rAd-N infection during first 24 h compared with the control DC infected by rAd-LacZ (P < 0.05 or P < 0.01). CONCLUSION It is suggested that N protein may be related to the excessive secretion of proinflammatory cytokines during SARS-CoV infection at the acute phase.


title: Recognition of mRNA cap structures by viral and cellular proteins.

text: Most cellular and eukaryotic viral mRNAs have a cap structure at their 5' end that is critical for efficient translation. Cap structures also aid in mRNA transport from nucleus to cytoplasm and, in addition, protect the mRNAs from degradation by 5' exonucleases. Cap function is mediated by cap-binding proteins that play a key role in translational control. Recent structural studies on the cellular cap-binding complex, the eukaryotic translation initiation factor 4E and the vaccinia virus protein 39, suggest that these three evolutionary unrelated cap-binding proteins have evolved a common cap-binding pocket by convergent evolution. In this pocket the positively charged N(7)-methylated guanine ring of the cap structure is stacked between two aromatic amino acids. In this review, the similarities and differences in cap binding by these three different cap-binding proteins are discussed. A comparison with new functional data for another viral cap-binding protein--the polymerase basic protein (PB2) of influenza virus--suggests that a similar cap-binding mechanism has also evolved in influenza virus.


title: Monkeypox in the United States: an occupational health look at the first cases.

text: Between May 15 and June 20, 2003, 71 suspected cases of monkeypox were investigated and 37 individuals in the United States developed laboratory confirmed monkeypox. These were the first cases of human monkeypox ever documented in the United States or in the Western Hemisphere. The disease was transmitted from small animals imported from Africa to other animals, including prairie dogs sold as pets throughout the U.S. Midwest. Direct contact with the infected animals was the method of infection, and although human to human transmission was thought to have occurred, this was not confirmed by follow up testing. Because of the link with contact with a prairie dog, initial evaluation of the disease was focused toward diseases commonly associated with this animal (e.g., tularemia, plague). Laboratory findings at the Marshfield Clinic in Marshfield, Wisconsin pointed to the presence of an orthopox. The CDC confirmed monkeypox was the infecting orthopox agent. Occupational health nurses from the Marshfield Clinic had direct involvement in the identification and follow up of employees who had direct contact with the diagnosed patients. Programs, such as a respiratory protection program initiated and carried out by Clinic occupational health nurses, were used to prevent employee exposure for Clinic staff. One Clinic employee was thought to potentially have monkeypox because of her direct contact with one of the patients. Four Clinic employees were vaccinated with vaccinia vaccine as a result of their contact with patients or lab specimens. Quarantine of the potentially infected employee and her boyfriend uncovered issues that must be addressed if other infectious diseases requiring quarantine or isolation of individuals emerge or re-emerge. These include a system to compensate individuals in quarantine or isolation who do not have any other source of income. The issue of whether workers' compensation should cover an employee who is quarantined or isolated for a potential work related exposure to an infectious disease if no disease is actually diagnosed also needs to be explored. A better system of getting state or CDC laboratory results back to the local level, including the occupational health area of the generating facility, must be developed. This will be very important if diseases such as severe acute respiratory syndrome (SARS) or smallpox should re-emerge in the United States. Occupational health nurses are an integral part of any infectious disease process occurring in the United States. The identification of monkeypox in the United States shows that any planning to detect, prevent, and treat diseases with the potential to affect the employee population must include occupational health nurse involvement.


title: Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

text: The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.


Severe acute respiratory syndrome and biology, air quality, physics, and mechanical engineering.


title: Feasibility of a Modified Biopsy Needle for Irreversible Electroporation Ablation and Periprocedural Tissue Sampling.

text: OBJECTIVES To test the feasibility of modified biopsy needles as probes for irreversible electroporation ablation and periprocedural biopsy. METHODS Core biopsy needles of 16-G/9-cm were customized to serve as experimental ablation probes. Computed tomography-guided percutaneous irreversible electroporation was performed in in vivo porcine kidneys with pairs of experimental (n = 10) or standard probes (n = 10) using a single parameter set (1667 V/cm, ninety 100 µs pulses). Two biopsy samples were taken immediately following ablation using the experimental probes (n = 20). Ablation outcomes were compared using computed tomography, simulation, and histology. Biopsy and necropsy histology were compared. RESULTS Simulation-suggested ablations with experimental probes were smaller than that with standard electrodes (455.23 vs 543.16 mm2), although both exhibited similar shape. Computed tomography (standard: 556 ± 61 mm2, experimental: 515 ± 67 mm2; P = .25) and histology (standard: 313 ± 77 mm2, experimental: 275 ± 75 mm2; P = .29) indicated ablations with experimental probes were not significantly different from the standard. Histopathology indicated similar morphological changes in both groups. Biopsies from the ablation zone yielded at least 1 core with sufficient tissue for analysis (11 of the 20). CONCLUSIONS A combined probe for irreversible electroporation ablation and periprocedural tissue sampling from the ablation zone is feasible. Ablation outcomes are comparable to those of standard electrodes.


title: Recombinant truncated nucleocapsid protein as antigen in a novel immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of severe acute respiratory syndrome coronavirus infection.

text: We report the development of an immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) for severe acute respiratory syndrome coronavirus (SARS-CoV) by using recombinant truncated SARS-CoV nucleocapsid protein as the antigen. The newly developed MAC-ELISA had a specificity and sensitivity of 100% as evaluated by using sera from healthy volunteers and patients with laboratory-confirmed SARS. Using serial serum samples collected from SARS patients, the times to seroconversion were determined by IgM antibody detection after SARS-CoV infection. The median time to seroconversion detection was 8 days (range, 5 to 17 days) after disease onset, and the seroconversion rates after the onset of illness were 33% by the first week, 97% by the second week, and 100% by the third week. Compared with the results of our previous report on the detection of IgG, the median seroconversion time by IgM detection was 3 days earlier and the seroconversion rate by the second week after the illness for IgM was significantly higher than by IgG assay. Our results indicating that the IgM response appears earlier than IgG after SARS-CoV infection in consistent with those for other pathogens. Our newly developed MAC-ELISA system offers a new alternative for the confirmation of SARS-CoV infection.


title: [Isolation and identification of SARS-coronavirus in nasal and throat swabs collected from clinically diagnosed SARS patients].

text: OBJECTIVE To isolate and identify SARS-coronavirus in nasal and throat swabs collected from clinically diagnosed severe acute respiratory syndrome (SARS) patients. METHODS Nasal and throat swab specimens were inoculated onto well of 24-well plate containing confluent monolayers of Vero and MRC-5 cells. Isolates were identified with serology, electron microscopy and genome sequence. RESULTS One hundred and fifty-eight nasal and throat swabs specimens from 79 SARS patients in Peking Union Medical College Hospital between April and May, 2003 were cultured for SARS-coronavirus. Cytopathic effect (CPE) was found in three nasal swab specimens inoculated in Vero cells. Acute and convalescent phase serum specimens collected from SARS patients were found with seroconversions and/or a fourfold or greater rises in indirect fluorescence antibodies (IgG and IgM) titers when the 3 isolates (infected Vero cells) were used as antigen. Coronavirus was observed in the culture supernatant by negative-stain electron microscopy. Genome sequence confirmed the isolates were SARS-coronavirus. CONCLUSIONS The 3 isolates from nasal and throat swabs samples collected from 79 clinically diagnosed SARS patients were SARS coronavirus.


title: Simultaneous detection of canine respiratory disease associated viruses by a multiplex reverse transcription-polymerase chain reaction assay.

text: A multiplex reverse transcription polymerase chain reaction (mRT-PCR) assay was developed for the simultaneous detection of canine distemper virus (CDV), canine respiratory coronavirus (CRCoV) and canine influenza virus (CIV). These viral pathogens are all causative agents of canine infectious respiratory disease (CIRD). The sensitivity and specificity of the mRT-PCR were determined by comparing it to a rapid antigen test (RAT) or immuno-chromatography test kit and reverse transcription-polymerase chain reaction (RT-PCR) in the detection of CDV, CRCoV and CIV antigens present in 100 clinical samples (nasal swabs and whole blood samples) from 50 dogs with respiratory disease symptoms. This study revealed that mRT-PCR had almost exactly the same performance or results were almost 100% in agreement with that of RT-PCR and RAT both in terms of the assay sensitivity and specificity which was more highly evident in detecting CIV, CDV and CRCoV antigens present in canine nasal swab samples. Therefore, this assay could be a better alternative for the definitive and simultaneous ante-mortem detection of the three viral pathogens that cause CIRD by using nasal swabs.


title: Virus-specific antibody, in the absence of T cells, mediates demyelination in mice infected with a neurotropic coronavirus.

text: Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1(-/-) mice lacking normal expression of activating Fc receptors (FcRgamma(-/-)) and by approximately 76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.


title: Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor.

text: The GP(1,2) envelope glycoproteins (GP) of filoviruses (marburg- and ebolaviruses) mediate cell-surface attachment, membrane fusion, and entry into permissive cells. Here we show that a 151-amino acid fragment of the Lake Victoria marburgvirus GP1 subunit bound filovirus-permissive cell lines more efficiently than full-length GP1. An homologous 148-amino acid fragment of the Zaire ebolavirus GP1 subunit similarly bound the same cell lines more efficiently than a series of longer GP1 truncation variants. Neither the marburgvirus GP1 fragment nor that of ebolavirus bound a nonpermissive lymphocyte cell line. Both fragments specifically inhibited replication of infectious Zaire ebolavirus, as well as entry of retroviruses pseudotyped with either Lake Victoria marburgvirus or Zaire ebolavirus GP(1,2). These studies identify the receptor-binding domains of both viruses, indicate that these viruses utilize a common receptor, and suggest that a single small molecule or vaccine can be developed to inhibit infection of all filoviruses.


title: Middle East respiratory syndrome novel corona MERS-CoV infection. Epidemiology and outcome update.

text: Middle East respiratory syndrome coronavirus MERS-CoV is a newly emerging respiratory virus with a high case fatality rate among identified cases. The virus is thought to cause a severe disease in patients with underlying comorbidities. The identification of asymptomatic patients and mild cases among family and healthcare worker contacts of confirmed cases indicates a wider spectrum of clinical manifestation of the disease. The majority of patients presented with fever 98%, fever with cough 83%, and shortness of breath 72%. Radiographic manifestations range from unilateral infiltrate 43%, to increased bronchovascular markings 17%, and diffuse reticulonodular pattern 4%. Our understanding of the epidemiology and clinical presentation of the disease is increasing overtime. It is still not known what the source of the virus is and what the best treatment modality should be.


Cardiac Tamponade from Coronary Artery Injury after Laparoscopic Anti-Reflux Surgery.


title: Sabadinine: a potential non-peptide anti-severe acute-respiratory-syndrome agent identified using structure-aided design.

text: A novel human coronavirus has been reported to be the causative agent of severe acute respiratory syndrome (SARS). Since replication of HcoVs depends on extensive proteolytic processing, the main proteinase, 3CLpro, is an attractive drug target for anti-SARS agents. We have employed molecular docking of a chemical database into the active site of 3CLpro to search for non-peptidyl inhibitors. One compound was identified to be the natural product sabadinine, isolated from a historical herbal remedy.


title: Virus maturation by budding.

text: Enveloped viruses mature by budding at cellular membranes. It has been generally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, or nucleocapsid). This model was particularly applicable to alphaviruses, which require both spike proteins and a nucleocapsid for budding. However, genetic studies have clearly shown that the retrovirus core protein, i.e., the Gag protein, is able to form enveloped particles by itself. Also, budding of negative-strand RNA viruses (rhabdoviruses, orthomyxoviruses, and paramyxoviruses) seems to be accomplished mainly by internal components, most probably the matrix protein, since the spike proteins are not absolutely required for budding of these viruses either. In contrast, budding of coronavirus particles can occur in the absence of the nucleocapsid and appears to require two membrane proteins only. Biochemical and structural data suggest that the proteins, which play a key role in budding, drive this process by forming a three-dimensional (cage-like) protein lattice at the surface of or within the membrane. Similarly, recent electron microscopic studies revealed that the alphavirus spike proteins are also engaged in extensive lateral interactions, forming a dense protein shell at the outer surface of the viral envelope. On the basis of these data, we propose that the budding of enveloped viruses in general is governed by lateral interactions between peripheral or integral membrane proteins. This new concept also provides answers to the question of how viral and cellular membrane proteins are sorted during budding. In addition, it has implications for the mechanism by which the virion is uncoated during virus entry.


Regulation of MHC class I and II antigens on cerebral endothelial cells and astrocytes following MHV-4 infection.


Anesthetic management of a patient after functional hemispherectomy using bilateral bispectral index monitoring.


title: Antigenic and genomic characterization of turkey enterovirus-like virus (North Carolina, 1988 isolate): identification of the virus as turkey astrovirus 2.

text: A small round virus (SRV) was isolated in 1988 from droppings of enteritis-affected turkeys in North Carolina and tentatively identified as an enterovirus on the basis of size (18-24 nm in diameter), intracytoplasmic morphogenesis, and a single-stranded RNA genome of approximately 7.5 kb. Additional characterization studies based on antigenic and genomic analyses were done to determine the relationship of this turkey enterovirus-like virus (TELV) to turkey astrovirus 2 (TAstV2), a recently characterized SRV of turkeys. Cross-immunofluorescence studies with TELV- and TAstV2-specific antisera indicated a close antigenic relationship between these viruses. TELV RNA was amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) procedures with oligonucleotide primers specific for TAstV2 polymerase gene (open reading frame [ORF] 1b) and capsid protein gene (ORF 2). Subsequent sequence analyses of these TELV-derived RT-PCR products indicated a high degree of similarity with polymerase gene (98.8%) and capsid gene (96.9%) of TAstV2. These studies definitively identify TELV (North Carolina, 1988 isolate) as TAstV2.


title: Structural proteins of bovine coronavirus and their intracellular processing.

text: The Quebec isolate of bovine coronavirus (BCV) was found to contain four unique major structural proteins. These proteins consisted of the peplomeric protein (gp190/E2, gp100/E2), the nucleocapsid protein (p53/N) and its apparent trimer (p160/N), a family of small matrix glycoproteins (gp26/E1, gp25/E1 and p23/E1) and the putative haemagglutinin (gp124/E3). Pulse-chase experiments utilizing polyclonal antiserum and monoclonal antibodies indicated that the unique BCV E3 protein had its primary precursor an N-linked glycoprotein with an Mr of 59,000 (gp59) which underwent rapid dimerization by disulphide bond formation to yield gp118. Further glycosylation of gp118 produced gp124/E3 which incorporated fucose. Thus gp124/E3 was probably a homodimer. The processing of the E2 and E1 proteins of BCV was similar to that shown previously for mouse hepatitis virus. A large N-linked precursor glycoprotein, gp170, underwent further glycosylation to yield gp190/E2 before subsequent proteolytic cleavage to yield gp100/E2. The glycosylated E1 (gp26, gp25) proteins arose as a result of O-linked glycosylation of p23/E1 as indicated by the resistance of these species to tunicamycin.


title: Epidemiologic herd-level assessment of causative agents and risk factors for winter dysentery in dairy cattle.

text: OBJECTIVE To test the association between exposure to bovine coronavirus (BCV) and outbreaks of winter dysentery (WD) in dairy herds and to examine other risk factors for outbreaks of WD in dairy herds. ANIMALS 12 dairy herds in Ohio affected with WD (case herds). For each case herd, 2 unaffected herds from the same area were concurrently used as control herds. PROCEDURE A case-control study was conducted, using herds as the unit of investigation. Multivariate logistic regression modeling was used to identify risk factors for contracting disease. RESULTS 4 factors appeared to increase a herd's risk for WD: increase in herd prevalence of adult cows that had a fourfold or more increase in BCV serum IgG antibody titer; increase in herd prevalence of adult cows that had a fourfold or more increase in bovine viral diarrhea virus (BVDV) titer; housing cattle in tiestall or stanchion barns rather than free-stall facilities; and use of equipment to handle manure and subsequently handle feed. The adjusted population-attributable risk for these variables was 71, 43, 53, and 31%, respectively, and 99% overall, indicating that these variables had considerable impact on WD outbreaks for the study population. CONCLUSIONS AND CLINICAL RELEVANCE In dairies in Ohio, recent herd exposure to BCV appeared to increase the risk for WD outbreaks. Some WD outbreaks might have been associated with acute BVDV infection. Certain housing and management practices may have increased the risk of an outbreak of WD.


[No time to waste; plea for scientific validity and against prolific authorship].


title: High rate of viral evolution associated with the emergence of carnivore parvovirus.

text: Canine parvovirus (CPV) is an emerging DNA virus that was first observed to cause disease in canines in 1978 and has since become a ubiquitous pathogen worldwide. CPV emerged from feline panleukopenia parvovirus (FPLV) or a closely related virus, differing at several key amino acid residues. Here we characterize the evolutionary processes underlying the emergence of CPV. Although FPLV has remained an endemic infection in its host populations, we show that, since the 1970s, the newly emerged CPV has undergone an epidemic-like pattern of logistic/exponential growth, effectively doubling its population size every few years. This rapid population growth was associated with a lineage of CPV that acquired a broader host range and greater infectivity. Recombination played no role in the emergence of CPV. Rather, any preexisting variation in the donor species and the subsequent rapid adaptation of the virus to canines were likely dependent on a high rate of mutation and the positive selection of mutations in the major capsid gene. Strikingly, although these single-stranded viruses have a DNA genome and use cellular replication machinery, their rate of nucleotide substitution is closer to that of RNA viruses than to that of double-stranded DNA viruses.


title: Isolation of coronaviruses antigenically indistinguishable from bovine coronavirus from wild ruminants with diarrhea.

text: Diarrheal feces from three sambar deer and one waterbuck in a wild animal habitat and one white-tailed deer on a wildlife farm in Ohio contained coronavirus particles which were agglutinated by antiserum to bovine coronavirus (BCV) in immune electron microscopy. Three coronavirus strains were isolated in human rectal tumor cells from the feces of the sambar and white-tailed deer and the waterbuck, respectively. Hemagglutination, receptor-destroying enzyme activity, indirect immunofluorescence, hemagglutination inhibition, virus neutralization, and Western blot (immunoblot) tests showed close biological and antigenic relationships among the isolates and with selected BCV strains. Gnotobiotic and colostrum-deprived calves inoculated with each of these isolates developed diarrhea and shed coronavirus in their feces and from their nasal passages. In a serological survey of coronavirus infections among wild deer, 8.7 and 6.6% of sera from mule deer in Wyoming and from white-tailed deer in Ohio, respectively, were seropositive against both of the isolates and selected BCV isolates by indirect immunofluorescence tests. These results confirm the existence of coronaviruses in wild ruminants and suggest that these species may harbor coronavirus strains transmissible to cattle.


title: Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method.

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that manifests itself in viral infection with fever, cough, shortness of breath, renal failure and severe acute pneumonia, which often result in a fatal outcome. MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed and is irredeemable with present technology. Genetic studies on MERS-CoV have shown that ORF 1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF 1ab replicase polyprotein may be used as suitable target for disease control. Viral activity can be controlled by RNA interference (RNAi) technology, a leading method for post transcriptional gene silencing in a sequence specific manner. However, there is a genetic inconsistency in different viral isolates; it is a great challenge to design potential RNAi (miRNA and siRNA) molecules which can silence the respective target genes rather than any other viral gene simultaneously. In current study four effective miRNA and five siRNA molecules for silencing of nine different strains of MERS-CoV were rationally designed and corroborated using computational methods, which might lead to knockdown the activity of virus. siRNA and miRNA molecules were predicted against ORF1ab gene of different strains of MERS-CoV as effective candidate using computational methods. Thus, this method may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of MERS-CoV, at genomic level.


title: Development of calpain-specific inactivators by screening of positional scanning epoxide libraries.

text: Calpains are calcium-dependent proteases that are required for numerous intracellular processes but also play an important role in the development of pathologies such as ischemic injury and neurodegeneration. Many current small molecule calpain inhibitors also inhibit other cysteine proteases, including cathepsins, and need improved selectivity. The specificity of inhibition of several calpains and papain was profiled using synthetic positional scanning libraries of epoxide-based compounds that target the active-site cysteine. These peptidomimetic libraries probe the P4, P3, and P2 positions, display (S,S)- or (R,R)-epoxide stereochemistries, and incorporate both natural and non-natural amino acids. To facilitate library screening, an SDS-PAGE assay that measures the extent of hydrolysis of an inactive recombinant m-calpain was developed. Individual epoxide inhibitors were synthesized guided by calpain-specific preferences observed from the profiles and tested for inhibition against calpain. The most potent compounds were assayed for specificity against cathepsins B, L, and K. Several compounds demonstrated high inhibition specificity for calpains over cathepsins. The best of these inhibitors, WRH(R,R), irreversibly inactivates m- and mu-calpain rapidly (k(2)/K(i) = 131,000 and 16,500 m(-1) s(-1), respectively) but behaves exclusively as a reversible and less potent inhibitor toward the cathepsins. X-ray crystallography of the proteolytic core of rat mu-calpain inactivated by the epoxide compounds WR gamma-cyano-alpha-aminobutyric acid (S,S) and WR allylglycine (R,R) reveals that the stereochemistry of the epoxide influences positioning and orientation of the P2 residue, facilitating alternate interactions within the S2 pocket. Moreover, the WR gamma-cyano-alpha-aminobutyric acid (S,S)-complexed structure defines a novel hydrogen-bonding site within the S2 pocket of calpains.


title: An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women.

text: OBJECTIVE AND DESIGN Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data. METHODS We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception. RESULTS We identified 10 new reports of which five were considered 'unlikely to inform the primary question'. We focus on the other five reports, along with nine from the previous review, which were considered 'informative but with important limitations'. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4. CONCLUSION Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.


title: Serum antibodies to bovine coronavirus in Swedish sheep.

text: Altogether 218 sheep sera from 40 flocks in different parts of Sweden were screened for antibodies to bovine coronavirus (BCV). Nineteen per cent of the sera were positive and there was a significantly higher frequency (p < 0.05) of at least one positive sample in flocks with more than 100 adult sheep than in smaller flocks. There was also a significantly higher frequency (p < 0.001) of positive samples from sheep older than 4 years than from younger ones. Only a weak relationship between BCV positivity (2 or more positive samples, p < 0.05) and cattle contact was demonstrated in this study. Possible transmission routes and other factors that could have affected the result are discussed. In light of our finding that all 5 sheep experimentally exposed to BCV through contact with infectious cow faeces seroconverted, we conclude that the antibodies found in Swedish sheep are probably the result of BCV infections directly or indirectly transmitted from cattle.


title: Risk and outbreak communication: lessons from alternative paradigms.

text: Risk communication guidelines widely used in public health are based on the psychometric paradigm of risk, which focuses on risk perception at the level of individuals. However, infectious disease outbreaks and other public health emergencies are more than public health events and occur in a highly charged political, social and economic environment. This study examines other sociological and cultural approaches from scholars such as Ulrich Beck and Mary Douglas for insights on how to communicate in such environments. It recommends developing supplemental tools for outbreak communication to deal with issues such as questions of blame and fairness in risk distribution and audiences who do not accept biomedical explanations of disease.


title: [Chlamydia-like and coronavirus-like agents found in dead cases of atypical pneumonia by electron microscopy].

text: OBJECTIVE To explore the causative agents of the atypical pneumonia (also SARS) occurred recently in some regions of our country. METHOD Organ samples of 7 dead cases of SARS were collected from Guangdong, Shanxi, Sichuan Provinces and Beijing for electron microscopic examination. 293 cell line was inoculated with the materials derived from the lungs to isolate causative agent(s). The agents in the organs and cell cultures were revealed by immunoassay. RESULTS Both Chlamydia-like and coronavirus-like particles were found in EM. Inclusion bodies containing elementary bodies, reticulate antibodies and intermediate bodies of Chlamydia-like agent were visualized in multiple organs from the 7 dead cases, including lungs (7 cases), spleens (2 cases), livers (2 cases), kidneys (3 cases) and lymph nodes (1 cases), by ultrathin section electron microscopy (EM). In some few sections, coronavirus-like particles were concurrently seen. A coronavirus RNA- polymerase segment (440 bp) was amplified from the lung tissues of two cases of the SARS. After inoculated with materials from the lung samples, the similar Chlamydia-like particles were also found in the inoculated 293 cells. Since the Chlamydia-like agents visualized in both organs and cell cultures could not react with the genus specific antibodies against Chlamydia and monoclonal antibodies against C. pneumoniae and C. psittaci, the results might well be suggestive of a novel Chlamydia-like agent. CONCLUSION Since the novel Chlamydia-like agent was found co-existing with a coronavirus-like agent in the dead cases of SARS, it looks most likely that both the agents play some roles in the disease. At the present time, however, one can hardly determining how did these agents interact each other synergetically, or one follows another, need further study.


Awareness-level information for veterinarians on weapons of mass destruction and preservation of evidence.


title: Bovine coronavirus nucleocapsid protein processing and assembly.

text: The coronavirus nucleocapsid protein (N) encapsidates the genomic RNA to form a helical nucleocapsid. The requirements for coronavirus nucleocapsid assembly are being studied. Two forms (approximately 50 kDa and 55 kDa) of the bovine coronavirus (BCV) N protein were detected in infected cells. However, only one form, a 50 kDa species, was detected in extracellular virions. After treatment with calf intestinal alkaline phosphatase (CIAP), the 55 kDa intracellular form increased in mobility to comigrate with the 50 kDa form; whereas, the 50 kDa intracellular species and N from extracellular virions was not sensitive to CIAP treatment. The data indicate that specificity exists with regard to assembly of N into the mature virion. The data suggests that processing of N may take place during assembly of either nucleocapsids or virions and that the processing may be a dephosphorylation event.


title: Respiratory viruses and asthma.

text: Viral infections have become increasingly recognized as a significant cause of asthma exacerbations, mainly because of improved viral detection techniques. Unfortunately, the ability to specifically treat viral infections and to limit the asthma morbidity associated with these agents has not kept pace with diagnostic technology. This article focuses on current concepts of the epidemiology of viruses in asthma exacerbations, investigations studying the physiologic and immunologic consequences of viral infection, and potential therapies to minimize virally-induced airway hyperresponsiveness. To impact this significant health problem, researchers must definitively ascertain the mechanisms by which viruses induce airway reactivity and must develop rational, safe approaches to prevent the consequences of viral infection in the patient with asthma.


title: [Recommendation for the diagnosis and treatment of novel coronavirus infection in children in Hubei (Trial version 1)].

text: Since December 2019, a cluster of patients have been diagnosed to be infected with 2019 novel coronavirus (2019-nCoV) in Wuhan, China. The epidemic has been spreading to other areas of the country and abroad. A few cases have progressed rapidly to acute respiratory distress syndrome and/or multiple organ function failure. The epidemiological survey has indicated that the general population is susceptible to 2019-nCoV. A total of 14 children (6 months to 14 years of age, including 5 cases in Wuhan) have been confirmed to be infected with 2019-nCoV in China so far. In order to further standardize and enhance the clinical management of 2019-nCoV infection in children, reduce the incidence, and decrease the number of severe cases, we have formulated this diagnosis and treatment recommendation according to the recent information at home and abroad.


Supply of Personal Protective Equipment (PPE) During the Covid-19 Pandemic.


title: Human LINE1 endonuclease domain as a putative target of SARS-associated autoantibodies involved in the pathogenesis of severe acute respiratory syndrome.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a disease with a mortality of 9.56%. Although SARS is etiologically linked to a new coronavirus (SARS-CoV) and functional cell receptor has been identified, the pathogenesis of the virus infection is largely unclear. METHODS The clinical specimens were processed and analyzed using an indirect enzyme-linked immunosorbent assay (ELISA) in-house. Further investigations of target antigen included reviews of phage display technique, rapid amplification of cDNA ends (RACE) technique, protein expression and purification, Western blotting validation, serological and immunohistochemical staining in postmortem tissue. RESULTS A type of medium or low titer anti-lung tissue antibodies were found in the sera of SARS patients at the early stage of the disease. Human long interspersed nuclear element 1 (LINE1) gene endonuclease (EN) domain protein was one of the target autoantigens and it was aberrantly expressed in the lung tissue of SARS patients. Anti-EN antibody was positive in the sera of 40.9% of SARS patients. CONCLUSIONS Human LINE1 endonuclease domain was identified as a putative target of SARS-associated autoantibodies, which were presented in the serum of SARS patients and may be involved in the pathogenesis of SARS.


title: Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths.

text: Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection. Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection. It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell. There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection. It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell. Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection. This article attempts to gather key information on arterial hypertension and COVID-19.


title: Evaluation of real-time reverse transcriptase PCR and real-time loop-mediated amplification assays for severe acute respiratory syndrome coronavirus detection.

text: We compared the performance of a recently established real-time loop-mediated amplification (LAMP) assay with the one from a highly sensitive quantitative PCR assay. None of these assays produced false-positive results in this study. For samples isolated from patients within the first 3 days of disease onset, the detection rate of the quantitative PCR assay was higher (14 of 15 were positive) than the LAMP assay (9 of 15 were positive). By contrast, the detection rates of these assays toward specimens sampled from patients with more than 3 days of illness were similar (32 of 44 for PCR and 33 of 44 for LAMP were positive). The simpler operation of LAMP might be a possible solution for on-site diagnosis.