title: Cigarette smoking among adults--United States, 2001.

text: One of the national health objectives for the United States for 2010 is to reduce the prevalence of cigarette smoking among adults to > or =12% (objective 27.1a). To assess progress toward this objective, CDC analyzed self-reported data from the 2001 National Health Interview Survey (NHIS). The findings of this analysis indicate that, in 2001, approximately 22.8% of U.S. adults were current smokers compared with 25.0% in 1993. During 1965-2001, smoking prevalence declined faster among non-Hispanic blacks aged > or =18 years than among non-Hispanic whites the same age. Preliminary data for January-March 2002 indicate a continuing decline in current smoking prevalence among adults overall. However, the overall decline in smoking is not occurring at a rate that will meet the national health objective by 2010. Increased emphasis on a comprehensive approach to cessation that comprises educational, economic, clinical, and regulatory strategies is required to further reduce the prevalence of smoking in the United States.


title: Mucosal immunization with recombinant adenoviruses: induction of immunity and protection of cotton rats against respiratory bovine herpesvirus type 1 infection.

text: To facilitate the evaluation of vaccines against bovine herpesvirus type 1 (BHV-1), a cotton rat model of intranasal (i.n.) BHV-1 infection was established. Cotton rat lung cells were similar to bovine cells in their ability to support BHV-1 replication in vitro. Furthermore, i.n. inoculation of cotton rats with BHV-1 resulted in pulmonary lesions comparable to BHV-1 infection in cattle. Using this model, the potential of i.n. and gastrointestinal (g.i.) immunization was examined with recombinant human adenoviruses expressing glycoprotein D (gD) of BHV-1 to induce protective immunity against BHV-1. The replication-competent virus (gD-dE3) was more efficient than the replication-defective virus (gD-dE1E3) in inducing gD-specific antibody in the serum and in the respiratory tract. Furthermore, i.n. immunization with gD-dE3 stimulated antigen-specific antibody-secreting cells in the lung 12 weeks following immunization. Protection against BHV-1 challenge correlated with gD-specific antibody levels such that i.n. immunization with gD-dE3 conferred complete protection, while g.i. immunization conferred only partial protection of the lungs of most animals against BHV-1 challenge. In comparison, immunization with gD-dE1E3 by either route resulted in only a partial reduction of BHV-1 titre in the respiratory tract. The results obtained demonstrate that mucosal immunization with replication-competent recombinant adenovirus expressing gD of BHV-1 can induce immunity and protection against BHV-1 challenge.


[Ⅳ.B-Cell Maturation Antigen(BCMA)-Targeting Therapy in Multiple Myeloma].


title: Molecular and seroepidemiological evidence of canine calicivirus infections in Japan.

text: Calicivirus infection of dogs was epidemiologically investigated by using canine calicivirus (CaCV) strain 48 as a reference. Similar RNA polymerase gene sequences and neutralizing antibodies against CaCV were detected in 1.7% of clinical specimens and 57% of serum samples, respectively, suggesting a high prevalence of CaCV in dog populations.


title: [Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19].

text: OBJECTIVE To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid. METHODS Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method. RESULTS There was no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria. CONCLUSIONS There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.


title: Airway management during a mass casualty event.

text: Mass casualty respiratory failure will lead to many challenges, not the least of which is safe and secure management of the victims' airways. These patients will be sicker than those typically managed in the operating room and will require more emergency management of their airways. Mass casualty incidents involving biological or chemical agents will pose the additional risk of exposure to pathogen. During the severe acute respiratory syndrome epidemic in Toronto, airway manipulation was clearly identified as the procedure most associated with risk to health care workers. Planning for scenarios such as these will require consideration of personal protection for health care workers to minimize these risks. Understanding the risks involved and the airway techniques required for each possible scenario will be key to planning and preparation.


title: Laboratory containment of SARS virus.

text: Following the severe acute respiratory syndrome (SARS) outbreak in 2003, a large number of clinical and environmental samples containing/potentially containing SARS coronavirus (SARSCoV) as well as SARS-CoV stocks were retained in clinical and research laboratories. The importance of laboratory biosafety was demonstrated by the occurrence of laboratory incidents in Singapore, Taiwan and Beijing. It is imperative that safe practice and techniques, safety equipment and appropriate facility design should be in place to reduce or eliminate exposure of laboratory workers, other persons and the outside environment to SARS-CoV containing materials. Discussion on laboratory containment of SARS-CoV was initiated in Hong Kong in August 2003. It was agreed that an inventory of all specimens with the potential presence of SARS-CoV collected for any diagnostic or research purposes from November 2002 to July 2003 should be established in each laboratory. They should be stored in a secure place at the appropriate biosafety level with access control. Un-needed samples collected during the period should be destroyed. These laboratories should be audited to ensure inventories are updated. The audit should include safety and security measures to detect irregularities. Any laboratory accidents involving materials suspected of containing SARS-CoV should be reported to the authorities and all personnel exposed closely followed medically. A contingency plan should be in place in the laboratory and a drill conducted regularly to test its efficacy. By January 2004, all clinical laboratories performing SARS-CoV testing in Hong Kong set up inventories to document location and types of SARS-CoV containing materials retained in their laboratory. Audits of these laboratories in 2004 showed that laboratory safety and containment requirements as recommended were generally met.


title: Epidemiological study of Culicoides hypersensitivity in horses in Israel.

text: The variations with breed, gender, age and coat colour in the prevalence of Culicoides hypersensitivity were studied in 408 horses on 18 farms in Israel. Data were gathered by means of questionnaires and the diagnoses were confirmed by direct physical examinations. The prevalence of Culicoides hypersensitivity was 28 per cent. The disease was rare on farms more than 800 m above sea level but was more prevalent at lower altitudes. The most important factors affecting the prevalence of Culicoides hypersensitivity were the farm, breed and age, but gender and colour were not significantly correlated with its prevalence.


title: SARS vaccine: progress and challenge.

text: Severe acute respiratory syndrome (SARS) emerged in 2002 as a severe and highly contagious infectious disease that rapidly spread to a number of different countries. The collaborative efforts of the global scientific community have provided, within a short period of time, substantial insights into the molecular biology and immunology of SARS-CoV. Although the outbreak has been contained, there is continuous concern that the virus may resurface into the human population through seasonal changes, animal reservoirs or laboratory accidents. The severe morbidity and mortality associated with SARS make it imperative that an effective vaccine be developed to prevent reemergence and epidemics in the future.


Evaluation of two antigen-capture ELISAs using polyclonal or monoclonal antibodies for the detection of bovine coronavirus.


title: Acute otitis media in neonatal life: a review.

text: Acute otitis media is frequently encountered by general practitioners and pediatricians. In the neonatal period acute otitis media may present as an isolated local infection or as part of septicemia. Diagnosis of the condition by otoscopy is difficult. Considering the wide spectrum of middle ear disorders (acute otitis media, otitis media with effusion, chronic suppurative otitis media) one can appreciate why opinions on the management of the condition are diverse. This is a review of the literature on clinical presentation, etiology, risk factors, treatment and prevention of acute otitis media in neonatal life.


title: Cough receptor sensitivity in children with acute and non-acute asthma.

text: BACKGROUND Cough is a major symptom in some children with asthma. The relationship between cough and the severity of asthma is ill defined. A study was undertaken to test the hypotheses that, in children with asthma who cough as a major part of their asthma symptoms, cough receptor sensitivity (CRS) is heightened during an acute severe exacerbation of asthma but not in the non-acute phase and airway calibre or its change correlates with CRS. METHODS Spirometric measurements and the capsaicin CRS test were performed on children admitted to hospital for an acute severe exacerbation of asthma. Nasal secretions were tested for viruses. The children were grouped into those who usually cough with asthma episodes and those who do not. The tests were repeated 7-10 days and 4-6 weeks later. The CRS outcome measure used was the concentration of capsaicin required to stimulate two (Cth) and five coughs (C5). RESULTS The CRS of the group who coughed (n = 15) was significantly higher than those who did not cough (n = 16) (mean difference log Cth 0.77 mumol (95% CI 0.35 to 1.18), C5 0.72 mumol (95% CI 0.26 to 1.18)) during acute asthma but not after the exacerbation. CRS was not significantly different between groups based on the presence of a viral infection. Neither forced expiratory volume in one second (FEV1) nor its change correlated with CRS nor its change. CONCLUSIONS In children with asthma CRS is heightened in acute severe asthma in the subgroup of children who have cough as a significant symptom with their asthma episodes. In acute and non-acute asthma CRS does not correlate with FEV1.


Wuhan Coronavirus (Covid-19): Yet Another Bat Virus Zoonotic.


title: Laparoscopic transperitoneal anterior adrenalectomy.

text: AIM Aim of this study was to report the authors' experience with the anterior transperitoneal approach, and with an anterior submesocolic approach in case of left sided lesions. MATERIAL AND METHODS From January 1994 to January 2011, 122 males and 170 females with a mean age of 50.7 years (range: 19-84) underwent laparoscopic adrenalectomy (LA) at 2 centers in Ancona and Rome (Italy) (that follow the same protocol). Fifteen patients underwent bilateral LA, the anterior transperitoneal approach was used in 233 cases (79.8%) and the anterior submesocolic in 59 (20.2%). One hundred and two patients had Conn's syndrome, 51 miscellaneous lesions, 55 Cushing's syndrome, 47 incidentalomas, 46 pheochromocytoma, 2 metastatic masses, 2 myelolipomas and 2 adrenogenital syndromes. The lesions had a mean diameter of 3.24 cm (range: 0.5-10). RESULTS Mean operating time was 120 minutes (range: 30-390). Conversion to open surgery was required in 13 cases (4,45%). Blood pressure and heart rate were stable during the operation. There were 5 major complications. Mobilization and resumption of diet occurred on the first postoperative day. Mean hospital stay was 4.32 days (range: 2-30). DISCUSSION Early identification and ligature of the adrenal vein, with minimal gland manipulation, are the major advantages, especially in case of pheochromocytoma. CONCLUSIONS Adrenal masses can be successfully treated using a laparoscopic transperitoneal anterior approach, in presence of a suitable anesthesiological and surgical team's experience. KEY WORDS Adrenal tumors, Laparoscopic adrenalectomy, Pheochromocytoma.


title: Comparison of molecular assays for the rapid detection and simultaneous subtype differentiation of the pandemic influenza A (H1N1) 2009 virus.

text: In April 2009, the H1N1 pandemic influenza virus emerged as a novel influenza virus. The aim of this study was to compare the performances of several molecular assays, including conventional reverse transcription polymerase chain reaction (RT-PCR), two real-time reverse transcription (rRT)-PCRs, and two multiplex RTPCRs. A total of 381 clinical specimens were collected from patients (223 men and 158 women), and both the Seeplex RV7 assay and rRT-PCR were ordered on different specimens within one week after collection. The concordance rate for the two methods was 87% (332/381), and the discrepancy rate was 13% (49/381). The positive rates for the molecular assays studied included 93.1% for the multiplex Seeplex RV7 assay, 93.1% for conventional reverse transcription (cRT)-PCR, 89.7% for the multiplex Seeplex Flu ACE Subtyping assay, 82.8% for protocol B rRT-PCR, and 58.6% for protocol A rRT-PCR. Our results showed that the multiplex Seeplex assays and the cRT-PCR yielded higher detection rates than rRT-PCRs for detecting the influenza A (H1N1) virus. Although the multiplex Seeplex assays had the advantage of simultaneous detection of several viruses, they were time-consuming and troublesome. Our results show that, although rRTPCR had the advantage, the detection rates of the molecular assays varied depending upon the source of the influenza A (H1N1)v virus. Our findings also suggest that rRT-PCR sometimes detected virus in extremely low abundance and thus required validation of analytical performance and clinical correlation.


title: Symptom profile of common colds in school-aged children.

text: BACKGROUND Signs and symptoms of a common cold reported in young children are those perceived by caretakers. Objective signs include cough, fever, and sneezing. Subjective symptoms include nasal congestion, feverishness, headache, and sore throat. School-aged children may provide a more accurate picture of the symptom profile during colds because they can self-report. METHODS Using preprinted diary sheets listing common signs and symptoms, diaries were kept for school-aged children for 10 days after onset of a cold. Nasopharyngeal aspirates were analyzed for respiratory viruses and potential bacterial pathogens. RESULTS Out of 81 colds studied, the most common signs were cough and sneezing, although the most common symptoms were nasal congestion and runny nose. Other symptoms, including feverishness and headache, were each reported in 15% of children at onset. The majority of children (73%) continued to be symptomatic 10 days after onset. Rhinovirus was detected in 46% and 1 or more potential bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) in 29% of episodes. Symptom profiles for rhinovirus illnesses and those in which potential pathogenic bacteria were detected were not different from the rest. CONCLUSION The common cold in school-aged children is characterized by nasal congestion, cough, and runny nose. Signs and symptoms usually continue for at least 10 days.


Inhibitor profile of porcine aminopeptidase W.


title: Biological properties of avian coronavirus RNA.

text: RNA with a sedimentation coefficient of 64S was isolated from infectious bronchitis virus, an avian coronavirus. The SNA contained a polyadenylic acid tract and was found to be infectious.


title: Characterization of antibody response to porcine reproductive and respiratory syndrome virus ORF5 product following infection and evaluation of its diagnostic use in pigs.

text: The sensitivity and specificity of recombinant open reading frame 5 products used in the Western blotting assay for confirmation of porcine reproductive and respiratory syndrome virus (PRRSV) serologic status were evaluated. The recombinant antigen-based assays were specifically compared with a commercial enzyme-linked immunosorbent assay (ELISA) for PRRSV antibodies using 1) PRRSV antibody-negative reference sera (n = 30), 2) naturally infected pig sera (n = 40), 3) sequential sera obtained from 24 experimentally infected pigs, and 4) sera submitted to 3 state diagnostic laboratories (n = 200). The recombinant antigen assay yielded an average increased sensitivity of 10% over the commercial PRRSV ELISA. The negative controls (group 1 sera) showed no difference between the 2 assays. This comparison confirmed that the recombinant antigen-specific assay was more sensitive than the commercial ELISA and is well suited for routine confirmation of the presence of PRRSV antibodies.


title: Coronaviruses in polarized epithelial cells.

text: Coronaviruses have a marked tropism for epithelial cells. In this paper the interactions of the porcine transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV-A59) with epithelial cells are compared. Porcine (LLC-PK1) and murine (mTAL) epithelial cells were grown on permeable supports. By inoculation from the apical or basolateral side both TGEV and MHV-A59 were found to enter the polarized cells only through the apical membrane. The release of newly synthesized TGEV from LLC-PK1 cells occurred preferentially from the apical plasma membrane domain, as evidenced by the accumulation of viral proteins and infectivity in the apical culture fluid. In contrast, MHV was released preferentially from the basolateral membrane of mTAL cells. The apical release of TGEV and the basolateral release of MHV may explain the in vivo establishment of a local and systemic infection, respectively.


title: Molecular differentiation of transmissible gastroenteritis virus and porcine respiratory coronavirus strains. Correlation with antigenicity and pathogenicity.

text: Transmissible gastroenteritis virus (TGEV) causes an economically important enteric disease of swine. Differences in the pathogenicity, antigenicity and tissue tropism have been observed among porcine coronaviruses. Although porcine respiratory coronavirus (PRCV) is antigenically similar but not identical to TGEV isolates, these respiratory coronaviruses differ markedly in pathogenicity and tissue tropism compared to TGEV isolates. Using a reverse transcriptase/polymerase chain reaction-restriction fragment length polymorphism (RT/PCR-RFLP) assay, TGEV and PRCV isolates were assigned to several distinct groups. By RFLP analysis of the 5' region of the S gene, TGEV strains were differentiated into 4 groups using the restriction enzyme Sau3AI. A fifth Sau3AI group contained the PRCV isolates. These 5 groups correlated with antigenic groups previously defined using monoclonal antibodies in our laboratory. Several restriction enzymes could be used to differentiate the TGEV strains into Miller and Purdue types. Analysis of a PCR amplified product in the 3 and 3-1 genes indicated the RT/PCR-RFLP assay results for TGEV Miller strains could be correlated with lower virulence created by passage in cell culture.


title: Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.

text: CONTEXT Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide. OBJECTIVES To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome. DESIGN, SETTING, AND PATIENTS Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined. MAIN OUTCOME MEASURES Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation. RESULTS Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P =.01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P =.03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation). CONCLUSIONS The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived.


title: Effect of metal removal on the toxicity of airborne particulate matter from the Utah Valley.

text: Epidemiological studies have linked the inhalation of airborne particulate matter (PM) to increased morbidity and mortality in humans. However, the mechanisms of toxicity of these particles remain unclear. Some hypotheses state that the toxicity might stem from PM transition metal content, adhered organic compounds, the biological component, or ultrafine particle content. In order to analyze metal involvement in PM toxicity, human airway epithelial cell line (BEAS-2B) cultures were exposed for 24 h to an aqueous extract of PM collected in the Utah Valley. A portion of the extract was treated with Chelex, an agent that removes cations (including transition metals) from solution. Removal of the majority of the metal mass was confirmed by inductively coupled plasma (ICP) analyses. Cells that were incubated with the untreated extract (62-1000 microg dry extract equivalent) showed a significant concentration-dependent increase in the inflammatory mediator interleukin-8 (IL-8) when compared to the control cells. However, cells incubated with Chelex-treated extract produced no change (relative to control) in IL-8. We exposed rats in vivo for 24 h to the same treatments as the cells and found significant increases in lactate dehydrogenase (LDH) and total protein in the rats exposed to the untreated extract and to the Chelex-treated extract with metals added back to achieve original concentrations. There was an attenuation of the observed LDH and total protein increases in the rats instilled with the Chelex-treated extract. Taken together, our results suggest that removal of metal cations attenuates cellular responses to the aqueous extract and support a role for transition metal involvement in PM-associated increases in morbidity and mortality.


title: [Advances in recently identified coronaviruses].

text: Coronaviruses are a large family of viruses which include viruses that cause the common cold and severe acute respiratory syndrome (SARS) in humans and other diseases in animals. There are considerable genetic diversities within coronaviruses due to their wide rang hosts and their special gene replication and transcription mechanisms. During this process, gene recombinations often occur, resulting in novel subtype or coronavirus emerge constantly. Of note are SARS-like-CoVs and novel HCoV-EMC identified in 2012. This minireview summarized major advances of recently identified coronaviruses, focusing on the genome structures and interspecies jumping mechanism of coronavirus.


title: Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors.

text: This study investigated the social capital of Iranian patients living with acquired immune deficiency syndrome (AIDS) and the associated factors. In a cross-sectional study the Integrated Social Capital Questionnaire was filled by a sequential sample of 300 patients visiting a referral counselling centre in Tehran. The patients' social capital scores were around 50% in the trust, social cohesion, collective action and cooperation and political empowerment domains. The groups and networks membership domain scored the lowest (27.1%). In regression analysis, employment status was significantly associated with groups and networks membership; age, marital status and financial status were associated with collective action and cooperation; period of disease awareness and marital status affected social cohesion and inclusion; and having risky behaviour affected empowerment and political action. Efforts are needed to enhance the social capital of those patients living with AIDS who are younger, unemployed, divorced/widowed, with risky behaviours and shorter disease awareness.


title: In vitro and in vivo anti-tobacco mosaic virus activities of essential oils and individual compounds.

text: Essential oils are increasingly of interest for use as novel drugs acting as antimicrobial and antiviral agents. In the present study, we report the in vitro antiviral activities of 29 essential oils, extracted from Chinese indigenous aromatic plants, against the tobacco mosaic virus (TMV). Of these essential oils, those oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass effected a more than 50% inhibition of TMV at 100 μg/ml. In addition, the mode of antiviral action of the active essential oils was also determined. Essential oils isolated from artemisia and lemongrass possessed potent inactivation and curative effects in vivo and had a directly passivating effect on TMV infection in a dose-dependent manner. However, all other active essential oils exhibited a moderate protective effect in vivo. The chemical constitutions of the essential oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass were identified by gas chromatography and gas chromatography-mass spectrometry. The major components of these essential oils were α-zingiberene (35.21%), limonene (76.25%), terpinen-4-ol (41.20%), limonene (80.95%), 1,8-cineole (27.45%), and terpinolene (10.67%). The curative effects of 10 individual compounds from the active essential oils on TMV infection were also examined in vivo. The compounds from citronellal, limonene, 1,8-cineole, and α-zingiberene effected a more than 40% inhibition rate for TMV infection, and the other compounds demonstrated moderate activities at 320 μg/ml in vivo. There results indicate that the essential oils isolated from artemisia and lemongrass, and the individual compound citronellal, have the potential to be used as an effective alternative for the treatment of tobacco plants infected with TMV under greenhouse conditions.


title: A randomised trial to evaluate the self-administered standardised chronic respiratory questionnaire.

text: The original chronic respiratory questionnaire (CRQ), one of the most widely used measures of health-related quality of life (HRQL) in chronic respiratory disease (CRD), is traditionally interviewer administered (IA) and includes an individualised dyspnoea domain. The present authors studied the impact of self-administered (SA) and standardised dyspnoea questions on CRQ measurement properties. In a factorial design multicentre trial, 177 patients with CRD (mean age 67.7 yrs; mean forced expiratory volume in one second per cent predicted 44.6%) were randomised to CRQ-IA (n = 86) or CRQ-SA (n = 91), and to initially complete the standardised or individualised items before and after respiratory rehabilitation. While maintaining validity, the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains. Compared with the standardised dyspnoea domain, the individualised dyspnoea domain indicated greater responsiveness. The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA. In conclusion, self-administration and standardisation of the chronic respiratory questionnaire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory questionnaire. These results challenge the assumption that interviewer-administered questionnaires are superior to self-administered questionnaires in older patients with chronic respiratory disease.


The case for New Zealand to have its own COVID-19 vaccine programme.


title: Use of the directional atherectomy for the treatment of femoro-popliteal lesions in patients with critical lower limb ischemia.

text: Femoro-popliteal PTA for the treatment of critical limb ischemia is frequently associated with unsatisfactory procedural success rates while directional atherectomy (DCA) has improved success rate since claudicant patients undergoing percutaneous treatment of femoro-popliteal obstructive disease. The aim of this prospective study is to evaluate the safety, efficacy and procedural success of DCA, at one year, in the percutaneous treatment of femoro-popliteal obstructive disease in patients with critical limb ischemia. METHODS From March 2012 to March 2013 18 consecutive patients with critical limb ischemia were treated with DCA (Turbohawk/Covidien-ev3 Endovascular Inc., North Plymouth, Minnesota, USA) for the treatment of femoro-popliteal obstructive disease. Patients were evaluated at 12 months. RESULTS Technical and procedural success was achieved in every patient. No in-hospital major adverse cardiovascular events occurred. Primary endpoint: freedom from any amputation was obtained in all patients. Secondary endpoints: clinical (Rutherford class improvement) and hemodynamic success (Ankle-brachial index improvement) was achieved in all patients. CONCLUSION The use of DCA for the treatment of femoro-popliteal obstructive disease is a safe and effective therapeutic strategy for patients with critical limb ischemia. The data included in our study should be considered hypothesis-generating in order to design of a randomized trial comparison with conventional PTA.


title: Preoperative caudal block prevents emergence agitation in children following sevoflurane anesthesia.

text: BACKGROUND The frequency of emergence agitation in children is increased following sevoflurane anesthesia. However, controversies still exist concerning the exact etiology of this postanesthetic problem. Although this phenomenon is present with adequate pain relief or even following pain-free procedures, pain is still regarded as a major contributing factor. METHODS In a prospective, randomized, double-blind study, we enrolled 48 premedicated and calm 2-6-year-old children undergoing inguinal hernia repair. We assigned children to one of two groups: children assigned to the caudal group (n = 24) received a caudal block to supplement sevoflurane, while children assigned to the fentanyl group (n = 24) received a bolus injection of 1 microg kg(-1) intravenous fentanyl before skin incision to supplement sevoflurane. In the post anesthesia care unit, all children were received by their parent, and the incidence of emergence agitation and pain scores, as well as hemodynamic changes, were compared in both groups. RESULTS Forty-four children completed the study. In the fentanyl group, 59% of the children were agitated following emergence from anesthesia as compared to 4.5% in the caudal group (P < 0.001). Also, pain scores, mean values of heart rate and blood pressure as well as morphine requirement were significantly higher in the post anesthesia care unit in the fentanyl group compared to the caudal group. CONCLUSION Our results show that in children undergoing inguinal hernia repair, pain control with a preoperative caudal block as compared to intraoperative intravenous fentanyl significantly reduces the incidence of emergence agitation and pain scores following sevoflurane anesthesia.


title: Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein.

text: Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. A substantial amount of S protein accumulates in the ER. The expression of S protein exerts different effects on the three major signaling pathways of the UPR. Particularly, it induces GRP78/94 through PKR-like ER kinase but has no influence on activating transcription factor 6 or X box-binding protein 1. Taken together, our findings suggest that SARS-CoV S protein specifically modulates the UPR to facilitate viral replication.


title: COVID-19 and the immune system.

text: A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease. While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression. Macrophages have shown a significant production of IL-6 suggesting they may contribute to the excessive inflammation in COVID-19 disease. Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections. In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3. Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role. Specific IgA response appears to be stronger and more persistent than IgM response. Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease.


title: The strategy of fusion genes construction determines efficient expression of introduced transcription factors.

text: The main goal in gene therapy and biomedical research is an efficient transcription factors (TFs) delivery system. SNAIL, a zinc finger transcription factor, is strongly involved in tumor, what makes its signaling pathways an interesting research subject. The necessity of tracking activation of intracellular pathways has prompted fluorescent proteins usage as localization markers. Advanced molecular cloning techniques allow to generate fusion proteins from fluorescent markers and transcription factors. Depending on fusion strategy, the protein expression levels and nuclear transport ability are significantly different. The P2A self-cleavage motif through its cleavage ability allows two single proteins to be simultaneously expressed. The aim of this study was to compare two strategies for introducing a pair of genes using expression vector system. We have examined GFP and SNAI1 gene fusions by comprising common nucleotide polylinker (multiple cloning site) or P2A motif in between them, resulting in one fusion or two independent protein expressions respectively. In each case transgene expression levels and translation efficiency as well as nuclear localization of expressed protein have been analyzed. Our data showed that usage of P2A motif provides more effective nuclear transport of SNAIL transcription factor than conventional genes linker. At the same time the fluorescent marker spreads evenly in subcellular space.


Mental Health Strategies to Combat the Psychological Impact of COVID-19 Beyond Paranoia and Panic.


The Art of Public Health in the Context of a Paradigm Shift.


title: [Molecular epidemiological and clinical features of coronavirus HKU1 in children with acute respiratory tract infection in Lanzhou].

text: OBJECTIVE Human coronavirus (CoV)-HKU1 (HCoV-HKU1) was first isolated by Woo et al in Hong Kong. Several successive reports confirmed retrospectively that this new human coronavirus was circulating in different countries worldwide. However, the impact and the role of the emerging HCoV-HKU1 were not defined in children with ARTI. The objective of this study was to investigate the molecular epidemiology and clinical characteristics of HCoV-HKU1 infection in children with ARTI in Lanzhou, China. METHOD Nasopharyngeal aspiration (NPA) samples were collected from 301 children with ARTI at the First Hospital of Lanzhou University, Gansu Province, China, between November 2007 and October 2008. Demographic data and clinical findings of these children were collected at the same time. The informed consent was obtained from their parents. This study protocol was approved by the hospital ethics committee. The reverse transcription polymerase chain reaction (RT-PCR) was employed to screen HCoV-HKU1. Furthermore, other common respiratory viruses were screened in HCoV-HKU1 positive samples. All PCR positive products were sequenced, and phylogenetic analysis was conducted. RESULT The overall frequency of HCoV-HKU1 infection was 5.0% (15/301). The HCoV-HKU1 pol gene sequences shared a 95.8% - 99.6% nucleotide identity with the human coronavirus-HKU1 strain, whereas the amino acid identity was 90.7% - 99.3%. The phylogenetic analysis revealed that the HCoV-HKU1 strain pol gene clustered with the HCoV-HKU1 strain N15 genotype B (no. DQ415911); 11 of 15 HCoV-HKU1 positive sample tested were mixed-infection. HCoV-HKU1 was detected only from November to April. Positive specimens peaked in November. Children with HCoV-HKU1 infection varied in age from 15 day to 12-years (median age, 10 months). The clinical diagnoses of HCoV-HKU1 positive patients included those with AURI and LURI. The clinical presentations of HCoV-HKU1 positive children included fever, cough, sputum production, diarrhea, vomiting; pharynx engorgement, crackles, and wheezing. The mean hospital stay of the 14 patients was 9.9 days. Six of 15 HCoV-HKU1 positive patients had an underlying illness, and they were all inpatients (hospital stay, mean, 11.2 days). There was no statistically significant difference in the detection rate between the two groups with and without underlying illnesses. CONCLUSION Human CoV-HKU1 infection exists in children with respiratory tract infections in Lanzhou region. A single HCoV-HKU1 genotype B was circulating locally. The symptoms and clinical diagnoses of those infected with HCoV-HKU1 had no specificity as compared with patients with other common respiratory viruses infection.


title: Analysis of cellular receptors for human coronavirus OC43.

text: Bovine coronavirus (BCV), human coronavirus OC43 (HCV-OC43) and hemagglutinating encephalomyelitis virus (HEV) are serologically related viruses that all have hemagglutinating activity. The receptor determinant for attachment to erythrocytes has been shown to be N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2). We compared the ability of the three coronaviruses to recognize 9-O-acetylated sialic acid and found that they all bind to Neu5,9Ac2 attached to galactose in either A2,3 or A2,6-linkage. There are, however, some differences in the minimum amount of sialic acid that is required on the cell surface for agglutination by these viruses. Evidence is presented that HCV-OC43 uses Neu5,9Ac2 as a receptor determinant not only for agglutination of erythrocytes but also for attachment to and infection of a cultured cell line, MDCK I cells.


title: Endovascular Treatment in Patients with Persistent Internal Carotid Artery Occlusion after Intravenous Tissue Plasminogen Activator: A Clinical Effectiveness Study.

text: BACKGROUND There has been no large-scale trial comparing endovascular treatment (add-on EVT) after intravenous tissue plasminogen activator (IV tPA) and IV tPA alone in acute ischemic stroke (AIS) caused by internal carotid artery occlusion (ICAO). We aimed at investigating the effectiveness and safety of add-on EVT after IV tPA in AIS patients with ICAO. METHODS Between March 2010 and March 2013, 3,689 consecutive ischemic stroke patients who were hospitalized within 4.5 h of onset were identified using a prospective stroke registry at 11 centers in Korea. Among them, patients with persistent ICAO after receiving IV tPA and whose 3-month modified Rankin Scale (mRS) was available were finally enrolled. A propensity score analysis with inverse-probability of treatment weighting was used to eliminate baseline imbalances between those receiving add-on EVT and IV tPA alone. RESULTS Among 264 patients enrolled in this study (mean age 71.4; male 56.4%; median National Institute of Health Stroke Scale score 15), 117 (44.3%) received add-on EVT. The add-on EVT group had a higher frequency of favorable outcome on the mRS ≤2 (35.0 vs. 18.4%; adjusted OR (aOR) 2.79; 95% CI 1.66-4.67) and lower mortality (17.9 vs. 35.4%; aOR 0.24; 95% CI 0.13-0.42) at 3 months, when compared to the IV tPA-alone group. Add-on EVT did not significantly increase the risk of symptomatic hemorrhage (5.1 vs. 4.1%; aOR 1.01; 95% CI 0.37-2.70). The rate of successful recanalization (thrombolysis in cerebral infarction grade ≥2b) in the add-on EVT group was 69.2%. CONCLUSIONS Compared to an IV tPA alone, add-on EVT can improve clinical outcomes in patients with symptomatic ICAO within 4.5 h of onset without a significant increase of symptomatic hemorrhage.


CONTAGIOUS DISEASES.


title: Mechanism of RNA recombination in carmo- and tombusviruses: evidence for template switching by the RNA-dependent RNA polymerase in vitro.

text: RNA recombination occurs frequently during replication of tombusviruses and carmoviruses, which are related small plus-sense RNA viruses of plants. The most common recombinants generated by these viruses are either defective interfering (DI) RNAs or chimeric satellite RNAs, which are thought to be generated by template switching of the viral RNA-dependent RNA polymerase (RdRp) during the viral replication process. To test if RNA recombination is mediated by the viral RdRp, we used either a purified recombinant RdRp of Turnip crinkle carmovirus or a partially purified RdRp preparation of Cucumber necrosis tombusvirus. We demonstrated that these RdRp preparations generated RNA recombinants in vitro. The RdRp-driven template switching events occurred between either identical templates or two different RNA templates. The template containing a replication enhancer recombined more efficiently than templates containing artificial sequences. We also observed that AU-rich sequences promote recombination more efficiently than GC-rich sequences. Cloning and sequencing of the generated recombinants revealed that the junction sites were located frequently at the ends of the templates (end-to-end template switching). We also found several recombinants that were generated by template switching involving internal positions in the RNA templates. In contrast, RNA ligation-based RNA recombination was not detected in vitro. Demonstration of the ability of carmo- and tombusvirus RdRps to switch RNA templates in vitro supports the copy-choice models of RNA recombination and DI RNA formation for these viruses.


title: The severe acute respiratory syndrome-coronavirus replicative protein nsp9 is a single-stranded RNA-binding subunit unique in the RNA virus world.

text: The recently identified etiological agent of the severe acute respiratory syndrome (SARS) belongs to Coronaviridae (CoV), a family of viruses replicating by a poorly understood mechanism. Here, we report the crystal structure at 2.7-A resolution of nsp9, a hitherto uncharacterized subunit of the SARS-CoV replicative polyproteins. We show that SARS-CoV nsp9 is a single-stranded RNA-binding protein displaying a previously unreported, oligosaccharide/oligonucleotide fold-like fold. The presence of this type of protein has not been detected in the replicative complexes of RNA viruses, and its presence may reflect the unique and complex CoV viral replication/transcription machinery.


title: [Comparison between tow methods of acute physiology and chronic health evaluation III and acute lung injury scale to evaluate the severity and prognosis of severe acute respiratory syndrome].

text: OBJECTIVE To evaluate the acute physiology and chronic health evaluation III (APACHE III) and acute lung injury (ALI) scale in the severity and prognosis of severe acute respiratory syndrome (SARS). METHODS The clinical data of 38 SARS patients, including survivors (24 cases) and no survivors (14 cases) were collected and evaluated with APACHE III and ALI scoring systems. The correlation of scores and prognosis was evaluated. RESULTS The scores of APACHE III in the non survivors were higher remarkably than those in the survivor group (P < 0.001). The scores of APACHE III had positive correlation with the overall fatality rate. When the scores of APACHE III was higher than 60, the mortality increased obviously (chi(2) = 3.886, P < 0.05). Elderly patients with SARS who were over 60 years old had a high mortality (chi(2) = 8.660, P < 0.05). The scores of ALI in the non survivors had not statistical significance than those in the survivor group (P = 0.127). CONCLUSIONS The score of APACHE III in the SARS are correlated with the patient's condition and prognosis. Elderly patients with SARS have a high mortality.


Management of Asthma in Children during COVID-19 Pandemic.


title: Major depression and somatic symptoms in a mind/body medicine clinic.

text: This study examined the prevalence of somatic symptoms and psychiatric characteristics of major depression in a Japanese psychosomatic outpatient clinic. A total of 2,215 outpatients referred for mind/body complaints were assessed by DSM-III-R or DSM-IV. Somatic symptoms were rated using the Cornell Medical Index Questionnaire. Ninety-one outpatients (4.1%) were diagnosed with major depression. Prevalence of fatigue (86%), insomnia (79%), nausea/vomiting (50%), and back pain (36%) as well as degrees of psychosocial stress (DSM-III-R axis IV) were higher (all p < 0.05) and scores of global assessment of psychosocial functioning (DSM-III-R/DSM-IV axis V) were lower (p < 0.001) in the major depressive patients compared to the remaining outpatients. Among the major depressive patients, the total number of somatic symptoms was larger (p < 0.05) in patients with 'severe' major depressive episodes than in those with 'mild' depressive episodes. These findings suggest that the level of depression is closely linked to the reporting of somatic symptoms in a psychosomatic medicine population.


title: Mapping of neutralizing epitopes to fragments of the bovine coronavirus E2 protein by proteolysis of antigen-antibody complexes.

text: Neutralizing antigenic domains on bovine coronavirus gp100/E2 were mapped to fragments of this protein by proteolytic cleavage and fragment analysis. The procedure involved analysis of fragments generated after incubation of E2-monoclonal antibody complexes with various proteases. The smallest antibody-bound fragments obtained were a 50K fragment following Staphylococcus aureus V8 protease and submaxillary protease digestion, and a 37K fragment following trypsin digestion. Trypsin also produced a transient antibody-bound 50K fragment. A 40K fragment which was not bound by antibody was observed following digestions with all three proteases. The 50K fragments generated by V8, submaxillary protease and trypsin comigrated on gels and displayed the same altered mobility under non-reducing conditions, suggesting identity of these fragments and indicating the presence of disulphide linkages in these fragments. The 40K fragments generated by these three enzymes also comigrated and displayed the same altered mobility under non-reducing conditions. The 37K trypsin fragment contained both neutralizing domains, A and B.


title: Replication of transmissible gastroenteritis coronavirus (TGEV) in swine alveolar macrophages.

text: Several strains of the enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV) have been shown to replicate in alveolar macrophages maintained in vitro. A distinct cytopathic effect was observed at a multiplicity of infection greater than or equal to 0.1. Infected cells released infectious virus. The extent of both virus production and cell destruction was highly dependent upon the virus input. At low input, cell viability was affected only slightly, and a delayed and persistent virus production could be observed. TGEV infection of macrophages also led to a marked synthesis of type I interferon. Thus, the possibility that alveolar macrophages act as an extra-intestinal target for TGEV must be considered.


title: Etiology of Balkan endemic nephropathy and associated urothelial cancer.

text: Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression to terminal renal failure. Evidence has accumulated that BEN is an environmentally induced disease. There are three actual theories attempting to explain the environmental cause of this disease: (1) the aristolochic acid hypothesis, which considers that the disease is produced by chronic intoxication with Aristolochia, (2) the mycotoxin hypothesis, which considers that BEN is produced by ochratoxin A, and (3) the Pliocene lignite hypothesis, which proposes that the disease is caused by long-term exposure to polycyclic aromatic hydrocarbons and other toxic organic compounds leaching into the well drinking water from low-rank coals in the vicinity to the endemic settlements. Moreover, it was suggested that BEN risk is influenced by inherited susceptibility. Therefore, it has been expected that molecular biological investigations will discover genetic markers of BEN and associated urothelial cancer, permitting early identification of susceptible individuals who may be at risk of exposure to the environmental agents. Since kidney pathophysiology is complex, gene expression analysis and highly throughput proteomic technology can identify candidate genes, proteins and molecule networks that eventually could play a role in BEN development. Investigation of gene-gene and gene-environment interactions could be the content of further studies determining the precise risk for BEN.


title: Applications of DNA microarrays in biology.

text: DNA microarrays have enabled biology researchers to conduct large-scale quantitative experiments. This capacity has produced qualitative changes in the breadth of hypotheses that can be explored. In what has become the dominant mode of use, changes in the transcription rate of nearly all the genes in a genome, taking place in a particular tissue or cell type, can be measured in disease states, during development, and in response to intentional experimental perturbations, such as gene disruptions and drug treatments. The response patterns have helped illuminate mechanisms of disease and identify disease subphenotypes, predict disease progression, assign function to previously unannotated genes, group genes into functional pathways, and predict activities of new compounds. Directed at the genome sequence itself, microarrays have been used to identify novel genes, binding sites of transcription factors, changes in DNA copy number, and variations from a baseline sequence, such as in emerging strains of pathogens or complex mutations in disease-causing human genes. They also serve as a general demultiplexing tool to sort spatially the sequence-tagged products of highly parallel reactions performed in solution. A brief review of microarray platform technology options, and of the process steps involved in complete experiment workflows, is included.


title: Characterization of White bream virus reveals a novel genetic cluster of nidoviruses.

text: The order Nidovirales comprises viruses from the families Coronaviridae (genera Coronavirus and Torovirus), Roniviridae (genus Okavirus), and Arteriviridae (genus Arterivirus). In this study, we characterized White bream virus (WBV), a bacilliform plus-strand RNA virus isolated from fish. Analysis of the nucleotide sequence, organization, and expression of the 26.6-kb genome provided conclusive evidence for a phylogenetic relationship between WBV and nidoviruses. The polycistronic genome of WBV contains five open reading frames (ORFs), called ORF1a, -1b, -2, -3, and -4. In WBV-infected cells, three subgenomic RNAs expressing the structural proteins S, M, and N were identified. The subgenomic RNAs were revealed to share a 42-nucleotide, 5' leader sequence that is identical to the 5'-terminal genome sequence. The data suggest that a conserved nonanucleotide sequence, CA(G/A)CACUAC, located downstream of the leader and upstream of the structural protein genes acts as the core transcription-regulating sequence element in WBV. Like other nidoviruses with large genomes (>26 kb), WBV encodes in its ORF1b an extensive set of enzymes, including putative polymerase, helicase, ribose methyltransferase, exoribonuclease, and endoribonuclease activities. ORF1a encodes several membrane domains, a putative ADP-ribose 1"-phosphatase, and a chymotrypsin-like serine protease whose activity was established in this study. Comparative sequence analysis revealed that WBV represents a separate cluster of nidoviruses that significantly diverged from toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses. The study adds to the amazing diversity of nidoviruses and appeals for a more extensive characterization of nonmammalian nidoviruses to better understand the evolution of these largest known RNA viruses.


title: [Delivery of a Healthy Newborn by the Partner of a Patient with CML Undergoing Treatment with Nilotinib].

text: A man in his 40s was diagnosed with CML. He and his partner expressed their desire to have a child. We recommended planning the pregnancy after the achievement of major molecular response and completion of TKI therapy because we could not promise complete safety of the fetus, However, he and his partner insisted on starting the TKI therapy immediately and planned the pregnancy during the therapy. The patient was started on nilotinib 600mg/body. CCyR, MMR, and CMR were achieved in 3, 8, and 12 months, respectively. The patient's partner got pregnant when he had been on TKI therapy for 15 months, and she gave birth to a healthy boy. Since many patients with CMLcan live for a long time after receiving TKI therapy, the quality of life of these patients is more important. Even if the percentage of patients with CML who are under 50 years of age is approximately 30%, the safety information of TKI with respect to pregnancy is unsatisfactory. Doctors struggle to address the problems of the patient's wish of childbearing, priority of TKI therapy, and fetal risks of the treatment. Although only a few cases of pregnancy and delivery of the partners of male patients with CML treated with TKI have been reported, all cases showed healthy childbirth and normal child growth. Our experience also showed that the partner of a male patient with CML treated with TKI became pregnant and delivered a healthy baby.


title: Rhinovirus detection by real-time RT-PCR in children with acute respiratory infection in Buenos Aires, Argentina.

text: Human rhinoviruses (HRV), the major cause of common colds, have a significant genetic diversity and are classified into 3 species (A, B, C) with more than 100 serotypes. HRV species C, described in 2006, can only be detected using molecular methods. The objectives of this paper were to adapt a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for HRV detection and to further determine the frequency of HRV in respiratory samples from children under 2 years of age, with acute respiratory infection (ARI), from Buenos Aires, Argentina. Two real-time RT-PCR assays amplifying the 207 base pair of the 5' non-coding region were compared. The original protocol includes locked nucleic acid analogues and a pyrimidine derivative in the forward primer, while the adapted protocol avoided those molecules. Of 67 respiratory samples, 17 (25.4 %) were positive with the original protocol, and 20 (29.9 %) with the adapted one. Discrepant results were confirmed by sequencing analysis. An expanded gold standard was defined to determine the performance of both assays, and was used to describe the clinical characteristics of positive patients. Better sensitivity and specificity were obtained with the adapted protocol. Considering the expanded gold standard, HRV were detected in 23/67 (34.3 %) patients with ARI: 8/18 (44.4 %) outpatients and 15/49 (30.6 %) hospitalized. Wheezing episodes were more frequent in HRV positive patients (43.5 %) than in HRV negative patients (18.2 %) (p = 0.041). This study describes the utility and clinical sensitivity of an adapted real-time RT-PCR assay for HRV detection.


title: [Delivery of oral health in andalusian health service on the de-escalation of SARS-CoV-2].

text: The pandemic declared by SARS-CoV-2 has meant a crisis in the health system that forced the urgent implementation of preventive public health measures. The respiratory transmission virus remains stable on surfaces, being able to spread by air in respiratory droplets or in procedures that generate aerosols. Dental activity is one of the professional sectors with the highest exposure index, both due to the generation of aerosols in most interventions, as well as the impossibility of maintaining a safe distance between patients and professionals. The postponement of scheduled and non-urgent healthcare activities in dental offices is one of the measures implemented to reduce the risk that it posed for the health and well-being of citizens. This report addresses the recommendations and measures to be taken into account to minimize risks in the Oral Health Units of the Andalusian Public Health System, to address the oral pathology of the population assigned in the scenario of improvement of the pandemic and its partial lack of confinement.


title: A technique of placing cuffed endotracheal tubes through in situ paediatric laryngeal mask airways.

text: If tracheal intubation is not possible using direct laryngoscopy, one option is to use a laryngeal mask airway (LMA) through which an endotracheal tube (ETT) can be passed. In children, however, the size of an uncuffed ETT that can pass through the lumen of an LMA is sometimes too small for the trachea, resulting in gas leakage around the ETT. Using a cuffed ETT may reduce the gas leak but withdrawal of the LMA is then prevented by the pilot balloon. In this study, the largest sizes of cuffed and uncuffed Mallinckrodt™ ETTs that could pass with ease through various sizes of paediatric Classic™ and ProSeal™ LMAs were documented. For cuffed ETTs, withdrawal of the LMA was made possible by simply cutting off the pilot balloon. The ETT cuff-inflating mechanism was then repaired by passing a 20 or 22 gauge cannula into the cut end of the inflating tubing. The proximal end of the cannula was then connected to a one-way valve or a three-way stopcock. This technique of cutting off the pilot balloon of the cuffed ETT made it possible to use paediatric cuffed ETTs in exchange for the LMAs tested. The task was easy to perform. Subsequent repair of the cuff-inflation tubing was effective and could withstand high pressures. These findings indicate that it is possible to pass cuffed ETTs through paediatric LMA lumens, which can provide ventilation without gas leaks, unlike uncuffed ETTs.


title: Isolation of a porcine respiratory, non-enteric coronavirus related to transmissible gastroenteritis.

text: A porcine respiratory, non-enteric virus which is related to the coronavirus transmissible gastroenteritis virus (TGEV) has been isolated in pigs and in cell culture. The isolate was designated TLM 83. It has become very widespread and enzootic among the swine population in Belgium and in other swine raising countries. It causes an infection of the lungs and appears to spread by aerogenic route. It does not replicate in the enteric tract. The experimental infection in conventional and gnotobiotic pigs in isolation remains subclinical. The infection, either experimental or in the field, results in the formation of antibodies which neutralise the classical enteric TGEV. Based on this relationship, this virus is assumed to be a new TGEV-related porcine respiratory coronavirus or TGEV itself which has totally lost its tropism for the enteric tract.


title: Isotype-specific antibody responses to bovine coronavirus structural proteins in serum, feces, and mucosal secretions from experimentally challenge-exposed colostrum-deprived calves.

text: Five newborn isolation-reared colostrum-deprived calves were inoculated orally and intranasally when they were 20 to 30 hours old and challenge exposed when they were 21 days old with a suspension of virulent bovine coronavirus (BCV). Blood, feces, nasal swabs, tears, saliva, and bronchoalveolar lavage (BAL) fluids were collected from each calf prior to inoculation and then weekly for 5 post-inoculation weeks. An ELISA was used to quantitate the immunoglobulin isotype titers of BCV antibodies in all samples. An immunoblot assay was used to determine the antibody isotype responses to BCV structural proteins in all the samples, except saliva. At postinoculation days 2 to 3, all calves had severe watery diarrhea, shed BCV in their feces, and had evidence of BCV replication in their upper respiratory tract. After challenge exposure, no calves became ill and no evidence of BCV replication in the respiratory or intestinal tracts was detected. At postinoculation week 1, IgM responses to the N protein were seen in mucosal secretions (except nasal fluid) and feces. At postinoculation weeks 2 and 3, IgA was predominant in mucosal secretions and feces directed toward all the BCV proteins (except the E2 protein in BAL fluid). After challenge exposure, an increase (or failure to decrease) in most IgA and some IgG1 titers to BCV proteins was seen. The increases in IgA titers were to all viral proteins in all mucosal secretions and feces, except to the N and E1 viral proteins in feces. The IgG1 titer increases were to the E2 proteins in tears and BAL fluid and to the E3 protein in BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Plasma-cell homing.

text: Recent studies indicate that chemoattractant cytokines (chemokines), together with tissue-specific adhesion molecules, coordinate the migration of antibody-secreting cells (ASCs) from their sites of antigen-driven differentiation in lymphoid tissues to target effector tissues. Developing ASCs downregulate the expression of receptors for lymphoid tissue chemokines and selectively upregulate the expression of chemokine receptors that might target the migration of IgA ASCs to mucosal surfaces, IgG ASCs to sites of tissue inflammation and both types of ASC to the bone marrow - an important site for serum antibody production. By directing plasma-cell homing, chemokines might help to determine the character and efficiency of mucosal, inflammatory and systemic antibody responses.


title: COVID-19: the effects on the practice of pediatric emergency medicine.

text: An informal survey of 65 pediatric emergency department leaders in North America-from 30 U.S. states and 4 Canadian provinces-revealed changes in operations, infrastructure, staffing, and clinical care that were undertaken as a result of the COVID-19 pandemic. The changes identified by the survey respondents were driven by reductions in pediatric patient volumes, a surge of adult patients, clinical considerations related to containment of infection, and financial factors. Survey respondents also reported effects of the pandemic on academic training programs and provider wellness. This report uses the survey responses to provide a snapshot of the adaptability of pediatric emergency medicine departments and clinicians during a public health emergency.


Postexposure prophylaxis with oseltamivir reduced influenza transmission in households.


title: Ebola Taught Value of Preparation, Vigilance.

text: The next fast-spreading infectious threat to community health is out there somewhere. Maybe it is deplaning from a long international flight with a host, ready to cut loose in an ill-monitored microbial haven where it can grow stronger, resist an antibiotic defense, then fan out in meandering, unpredictable attack.


title: Encapsidation studies of poliovirus subgenomic replicons.

text: The inclusion of a foreign marker gene, chloramphenicol acetyltransferase (CAT) gene, into the poliovirus genome allows its replication and encapsidation to be easily monitored using a simple enzyme assay. Such poliovirus replicons require the presence of helper virus for their successful propagation and thus are similar to defective interfering (DI) viruses. In genomes containing the CAT gene, the majority of the P1 virus capsid region of the poliovirus genome could be removed without destroying viability. The smallest replicon was significantly smaller than any naturally occurring DI particle so far reported, yet it retained the ability to replicate and be encapsidated by structural proteins provided by helper virus in trans. The efficiency with which the replicons were encapsidated was investigated using a direct immunostaining technique that allows individual cells infected with either a replicon or helper virus to be quantified. These results were compared to the frequencies of trans-encapsidation of polioviruses and coxsackievirus B4 using a two-stage neutralization assay. Poliovirus types 1, 2 and 3 but not coxsackievirus B4, coxsackievirus A21 or rhinovirus 14 provided efficient trans-encapsidation of poliovirus type 3 or type 3-derived replicons. These results suggest that a specific encapsidation process operates and that it does not involve RNA sequences within the region of the genome encoding the capsid proteins.


The effective use of the media during an infectious disease emergency.


title: Poliovirus infection enhances the formation of two ribonucleoprotein complexes at the 3' end of viral negative-strand RNA.

text: To identify proteins involved in the formation of replication complexes at the 3' end of poliovirus negative-strand RNA, a combined in vitro biochemical and in vivo genetic approach was used. Five subgenomic cDNA constructs were generated to transcribe different negative-strand RNA fragments. In UV cross-linking assays, distinct differences in binding of proteins in extracts from poliovirus-infected and uninfected cells to virus-specific, radiolabeled transcripts were observed. Two proteins present in extracts from poliovirus-infected cells with approximate molecular masses of 36 and 38 kDa were shown to cross-link to the 3' end of poliovirus negative-strand RNA. Appearance of the 36- and 38-kDa proteins in UV cross-linking assays can be detected 3 to 3.5 h after infection, and cross-linking reaches maximum levels by 5 h after infection. The binding site for the 36-kDa protein overlaps with the computer-predicted loop b region of stem-loop I, the so-called cloverleaf structure, and the RNA sequence of this region is required for efficient binding. Transfection of full-length, positive-sense RNA containing a five-nucleotide substitution (positions 20 to 25) in the loop b region of stem-loop I into tissue culture cells yielded only viral isolates with a reversion at position 24 (U-->C). This finding demonstrates that the wild-type cytidine residue at position 24 is essential for virus replication. RNA binding studies with transcripts corresponding to the 3' end of negative-strand RNA suggest that complex formation with the 36-kDa protein plays an essential role during the viral life cycle.


Severe atypical pneumonia outbreak associated with influenza A(H1N1)pdm09 in Egypt, 2013–2014 season.


Hand hygiene in preventing COVID-19 transmission.


Registries and informed consent.


title: Norovirus recombination.

text: RNA recombination is a significant driving force in viral evolution. Increased awareness of recombination within the genus Norovirus of the family Calicivirus has led to a rise in the identification of norovirus (NoV) recombinants and they are now reported at high frequency. Currently, there is no classification system for recombinant NoVs and a widely accepted recombinant genotyping system is still needed. Consequently, there is duplication in reporting of novel recombinants. This has led to difficulties in defining the number and types of recombinants in circulation. In this study, 120 NoV nucleotide sequences were compiled from the current GenBank database and published literature. NoV recombinants and their recombination breakpoints were identified using three methods: phylogenetic analysis, SimPlot analysis and the maximum chi2 method. A total of 20 NoV recombinant types were identified in circulation worldwide. The recombination point is the ORF1/2 overlap in all isolates except one, which demonstrated a double recombination event within the polymerase region.


The role of endoscopy in dyspepsia.


title: Ensuring good governance to address emerging and re-emerging animal disease threats: supporting the veterinary services of developing countries to meet OIE international standards on quality.

text: As an effect of increased globalisation, animal diseases, in particular those transmissible to man, have an immediate global economic and social impact. This fact, dramatically illustrated by the current avian influenza epizootic in South-East Asia and Eastern Europe, clearly demonstrates the crucial importance of the national Veterinary Services (VS) for the prevention, early detection and response for the efficient control of animal diseases. Complying with this mission for the VS presupposes the existence of appropriate governance and legislation and of an official system to control their quality and reliability- an obvious weakness in many developing and in transition countries. The World Organisation for Animal Health (OIE) has therefore developed a project aiming at strengthening the VS in those countries facing the greatest animal health threats and to bring them into line with OIE international standards already adopted by the same countries. Based on the evaluation of the VS and subsequent actions at the global, regional and national levels, the project will have a significant beneficial impact on the targeted countries as well as the international community as a whole, not only in the fields of agriculture, food security and production, and food safety, but also for the local and global prevention of emerging and re-emerging diseases of veterinary and public health importance. The project will be implemented in strong collaboration with the Food and Agriculture Organization. The actions proposed must be considered eligible for the concept of International Public Good.


[De første kliniske data fra RASi-behandlede indlagte patienter med COVID-19 kommer nu, og vi skal ikke ændre medicinering].


title: Clinical, hematological, and biochemical findings in puppies with coronavirus and parvovirus enteritis.

text: The clinical and laboratory findings in puppies naturally infected with canine coronavirus (CCoV) and/or canine parvovirus (CPV) were compared with findings in uninfected puppies. Lymphopenia was the only parameter related to CCoV infection that was statistically significant; vomiting, anorexia, lethargy, hemorrhagic fluid diarrhea, leukopenia, lymphopenia, thrombocytopenia, hypoglycemia, and hypoproteinemia were correlated with CPV infection.


title: Thoughts about Dying in America: Enhancing the impact of one's life journey and legacy by also planning for the end of life.

text: This Perspective offers a summary of the recommendations in the Institute of Medicine report Dying in America How we die is a deeply personal issue that each of us will face. However, the approach to end-of-life (EOL) care in the United States needs improvement. Too frequently, healthcare delivery is uncoordinated and has many providers who are not adequately prepared to have meaningful conversations about EOL planning. This is amplified by payment systems and policies that create impediments, misunderstanding, and sometimes misinformation. Dying in America made five recommendations to improve quality and honor individual preferences near the EOL beginning with making conversations with providers and families something that occurs during various phases of the life cycle and not just when one is facing serious illness or possible EOL. It was recommended (i) that public and private payers and care delivery organizations cover the provision of comprehensive care that is accessible and available to individuals on a 24/7 schedule; (ii) that professional societies and other entities establish standards for clinician patient communication and advance care planning and that payers and care delivery organizations adopt them; (iii) that educational institutions, credentialing bodies, accrediting boards, state regulatory agencies, and care delivery organizations establish palliative care training, certification, and/or licensure requirements; (iv) that public and private payers and care delivery organizations integrate the financing of health and social services; and (v) that public and private organizations should engage their constituents and provide fact-based information to encourage advance care planning and informed choice.


title: Structure and encapsidation of transmissible gastroenteritis coronavirus (TGEV) defective interfering genomes.

text: Serial undiluted passages were performed with the PUR46 strain of TGEV in swine testis (ST) cells. Total cellular RNA was analyzed at different passages after orthophosphate metabolic labeling. Three new defective RNA species of 24, 10.5, and 9.5 kb (DI-A, DI-B, and DI-C respectively) were detected at passage 30, which were highly stable and significantly interfered with helper mRNA synthesis in subsequent passages. By Northern hybridization DIs A, B, and C were detected in purified virions at amounts similar to those of helper RNA. Standard and defective TGEV virions could be sorted in sucrose gradients, indicating that defective and full-length genomes are independently packaged. cDNA synthesis of DI-B and DI-C RNAs was performed by the reverse transcription-polymerase chain reaction (RT-PCR) to give four fragments in each case. Cloning and sequencing of the DI-C PCR products showed that the smallest DI particle comprises 9.5 kb and has 4 discontinuous regions of the genome. It contains 2.1 kb from the 5'-end of the genome, about 7 kb from gene 1b, the first 24 nucleotides of the S gene, 12 nucleotides of ORF 7, and the 0.4 kb of the UTR at the 3'-end.


title: [Quality of interaction database management systems].

text: OBJECTIVE To identify drug interaction databases (DID) and assess the quality of their structures. METHOD A search was made of the literature for DID and a series of exclusion and structural quality criteria were defined (at least four quality criteria: Classification according to severity, classification according to level of evidence, bibliographical reference data, description of clinical management and 11 criteria used for weighting). The level of compliance of every DID with the criteria defined was analysed, together with the level of compliance of each criteria in each DID. RESULTS A total of 54 DID were identified, 30 of which complied with exclusion criteria and 15 of which did not meet the minimum criteria. The rest of the criteria were evaluated in nine DID: Bot-plus and Medinteract (100 %), SEFH Guide, Lexi-interact and Medscape (89 %), Hansten (83 %), Micromedex and Stockley (78 %), Drug Interactions Facts (68 %). Ninety-two per cent of the DID describe the mechanism of action, 87 % classify the information according to the active ingredient, 75 % do not state they have any conflict of interest, classify according to level of severity, have electronic format and are easy to search. A total of 67 % are specific DID, 62 % are classified according to level of evidence, contain bibliographical references and describe clinical management. CONCLUSIONS A third of the DID comply with the minimum criteria. Differences were observed in the level and compliance criteria among Spanish and foreign DID. Some of the main DID used as references in the bibliography have significant structural defects: no web presentation, no multi-check function and others.


title: Mutagenesis analysis of the nsp4 main proteinase reveals determinants of arterivirus replicase polyprotein autoprocessing.

text: Nonstructural protein 4 (nsp4; 204 amino acids) is the chymotrypsin-like serine main proteinase of the arterivirus Equine arteritis virus (order Nidovirales), which controls the maturation of the replicase complex. nsp4 includes a unique C-terminal domain (CTD) connected to the catalytic two-beta-barrel structure by the poorly conserved residues 155 and 156. This dipeptide might be part of a hinge region (HR) that facilitates interdomain movements and thereby regulates (in time and space) autoprocessing of replicase polyproteins pp1a and pp1ab at eight sites that are conserved in arteriviruses. To test this hypothesis, we characterized nsp4 proteinase mutants carrying either point mutations in the putative HR domain or a large deletion in the CTD. When tested in a reverse genetics system, three groups of mutants were recognized (wild-type-like, debilitated, and dead), which was in line with the expected impact of mutations on HR flexibility. When tested in a transient expression system, the effects of the mutations on the production and turnover of replicase proteins varied widely. They were cleavage product specific and revealed a pronounced modulating effect of moieties derived from the nsp1-3 region of pp1a. Mutations that were lethal affected the efficiency of polyprotein autoprocessing most strongly. These mutants may be impaired in the accumulation of nsp5-7 and/or suffer from delayed or otherwise perturbed processing at the nsp5/6 and nsp6/7 junctions. On average, the production of nsp7-8 seems to be the most resistant to debilitating nsp4 mutations. Our results further prove that the CTD is essential for a vital nsp4 property other than catalysis.


Development of rapid assay for screening compounds for antiviral activity against RNA viruses.


title: Novel nonnucleoside inhibitor of hepatitis C virus RNA-dependent RNA polymerase.

text: A novel nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), [(1R)-5-cyano-8-methyl-1-propyl-1,3,4,9-tetrahydropyano[3,4-b]indol-1-yl] acetic acid (HCV-371), was discovered through high-throughput screening followed by chemical optimization. HCV-371 displayed broad inhibitory activities against the NS5B RdRp enzyme, with 50% inhibitory concentrations ranging from 0.3 to 1.8 microM for 90% of the isolates derived from HCV genotypes 1a, 1b, and 3a. HCV-371 showed no inhibitory activity against a panel of human polymerases, including mitochondrial DNA polymerase gamma, and other unrelated viral polymerases, demonstrating its specificity for the HCV polymerase. A single administration of HCV-371 to cells containing the HCV subgenomic replicon for 3 days resulted in a dose-dependent reduction of the steady-state levels of viral RNA and protein. Multiple treatments with HCV-371 for 16 days led to a >3-log10 reduction in the HCV RNA level. In comparison, multiple treatments with a similar inhibitory dose of alpha interferon resulted in a 2-log10 reduction of the viral RNA level. In addition, treatment of cells with a combination of HCV-371 and pegylated alpha interferon resulted in an additive antiviral activity. Within the effective antiviral concentrations of HCV-371, there was no effect on cell viability and metabolism. The intracellular antiviral specificity of HCV-371 was demonstrated by its lack of activity in cells infected with several DNA or RNA viruses. Fluorescence binding studies show that HCV-371 binds the NS5B with an apparent dissociation constant of 150 nM, leading to high selectivity and lack of cytotoxicity in the antiviral assays.


title: Crossing of infrainguinal peripheral arterial chronic total occlusion with a blunt microdissection catheter.

text: PURPOSE Crossing of lower-extremity arterial chronic total occlusion (CTO) can be challenging. Use of the Viance peripheral CTO crossing device (Covidien) in the superficial femoral (SFA), popliteal, and below-the knee (BTK) arterial locations has received limited study. METHODS Fifty-eight patients from the Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851) were treated between April 2010 and November 2013 with the Viance device. The procedural and 30-day clinical outcomes were collected. RESULTS Mean age was 65.5 ± 8.7 years and 55.1% had diabetes mellitus. Most lesions (n = 58) were TASC classification type C (n = 16; 27.6%) and D (n = 16; 27.6%), with mean lesion length 140.0 ± 71.0 mm; 93.1% of lesions were de novo and 81.0% were severely calcified. Technical success (crossing without the use of a reentry device) was achieved in 87.9% of cases and procedural success was obtained in 86.2%; 51.7% of lesions received stents, with the remaining treated with balloon angioplasty and/or atherectomy. Average fluoroscopy time was 39.1 ± 21.2 min, with 187.8 ± 72.0 mL of contrast and 210.0 ± 212.0 Gy cm² radiation dose-area product. There was 1 periprocedural complication (access-site hematoma treated conservatively without blood transfusion). At 30 days post procedure, there was significant improvement in ankle-brachial index (0.72 ± 0.30 to 0.84 ± 0.16; P=.01) and Rutherford class (3.33 ± 0.81 to 1.54 ± 1.47; P<.001). Clinically-indicated target vessel revascularization, surgical intervention or amputation at 30 days was 5.2%. CONCLUSION Use of Viance to cross infrainguinal arterial CTO was associated with high success, low complication rates, and significant symptom improvement.


title: [Transmissible gastroenteritis of swine: stability of coronavirus in gastric and intestinal contents].

text: Low and high passaged cell culture strains of TGE coronavirus were examined for stability in gastric and small intestine juices collected in 3-6 month-old pigs killed at different times after last feeding. Results revealed high fragility of the TGE virus in these digestive liquids. Differences in stability were observed between strains of TGE virus. But no correlation could be made between the level of stability and cell passage status of the virus strain. We conclude that the stability of TGE coronavirus in gastric and small intestine juices could not be considered as a genetic marker of virulence. In future, it will be necessary to take into account these data concerning fragility of TGE coronavirus for improvement of oral vaccination methods in pregnant sows using a live virus vaccine.


title: Assessment of chemical libraries for their druggability.

text: High throughput virtual screening is acknowledged as the initial means for identifying hit compounds that will be eventually transformed to leads or drug candidates. To improve quality of screening, it is essential to have powerful methods for the analysis of the compound databases. For this purpose, we have developed a novel and practical scoring function to assess the druggability of compounds. The proposed function consists of 12 metrics that take into account physical, chemical and structural properties as well as the presence of undesirable functional groups. We have applied this 12-metric scoring function to 44 different databases that include more than 3.8 million compounds, which are commercially available. The overall quality of each database was evaluated according to the score and rank measured by our 12-metric function. Our findings suggest that, the majority of compounds that do not satisfy druggable rules do so due to high molecular weight, high logP values and the presence of reactive functional groups.


title: Reducing health disparity in Taiwan: quantifying the role of smoking.

text: OBJECTIVE To assess the impact of smoking disparities on health disparities, in terms of gap in life expectancy, in Taiwan cities and counties. METHODS Using the decomposition method of life expectancy, the contribution of each disease category to the life expectancy gap was quantitatively expressed as the number of years of life. The smoking attributable fraction (SAF) was calculated for each city and county based on their respective smoking prevalence and relative risk for each smoking related disease. The smoking attributable gap (SAG) in life expectancy between two sites is the sum of the difference in SAF between two sites for each smoking related disease multiplied by the number of years this disease contributed to the life expectancy gap. RESULTS Significant health and smoking disparities were present among the 23 cities and counties in Taiwan. These health disparities and smoking disparities were highly correlated (R2 = 0.3676). Generally, the health gap increased with increasing smoking disparity. The disparity in smoking prevalence and intensity among cities and counties in Taiwan was responsible for up to 19% of the health disparity. The health disparity is also highly correlated (R2 = 0.3745) with SAG in life expectancy. CONCLUSIONS Reducing smoking is important to health, and reducing the smoking disparity is also important for reducing the health disparity observed in Taiwan. The larger the health disparity is, the more important the smoking attributable disparity could be. The reduction of smoking disparities could be a realistic and cost effective way toward reducing health disparities.


title: Severe acute respiratory syndrome.

text: Severe acute respiratory syndrome (SARS) is a form of atypical pneumonia that apparently originated in Guangdong Province of the People's Republic of China in late 2002. This first came to the world's attention in late February 2003, and has since spread worldwide. As of June 23rd 2003, the disease had been reported from 32 countries or regions globally, affecting 8459 people; 805 individuals (9.5 % of the total affected) have died of the disease. A novel coronavirus, the SARS-associated coronavirus (SARS- CoV) has been found in various specimens taken from patients with SARS. Although there has been rapid development of tests to detect SARS Co-V, these tests presently have certain limitations. Definitions of suspected, confirmed and probable cases have been formulated. Measures currently used for the management of patients with SARS include isolation, ribavirin, corticosteroid therapy and mechanical ventilation. Unfortunately, almost 10 % of affected patients succumb to their illness, underlying the need for developing more effective therapy. It remains to be seen how long it will take to bring this epidemic under control.


title: An evaluation of SARS and droplet infection control practices in acute and rehabilitation hospitals in Hong Kong.

text: 1. This study has demonstrated that great efforts have been made by the Hospital Authority and the studied hospital cluster to contain and prevent infection, and that high levels of vigilance have been enforced in anticipation of future outbreaks of SARS and other droplet infections. 2. Most health care workers and support workers have good hospital infection control and isolation precaution knowledge levels. 3. Compliance with infection control guidelines is satisfactory and has increased compared with previous studies. 4. Most participants had positive perceptions of the guidelines and found the training programmes useful. 5. This study has identified several structures and infection control practice areas that need strengthening, including improving the clarity of some guidelines and minimising barriers to their implementation.


Interactions of cellular proteins with the positive strand of 3'-untranslated region RNA and the nucleoprotein gene of porcine reproductive and respiratory syndrome virus.


title: Timeliness of epidemiological outbreak investigations in peer-reviewed European publications, January 2003 to August 2013.

text: Timely outbreak investigations are central in containing communicable disease outbreaks; despite this, no guidance currently exists on expectations of timeliness for investigations. A literature review was conducted to assess the length of epidemiological outbreak investigations in Europe in peer-reviewed publications. We determined time intervals between outbreak declaration to hypothesis generation, and hypothesis generation to availability of results from an analytical study. Outbreaks were classified into two groups: those with a public health impact across regions within a country and requiring national coordination (level 3) and those with a severe or catastrophic impact requiring direction at national level (levels 4 and 5). Investigations in Europe published between 2003 and 2013 were reviewed. We identified 86 papers for review: 63 level 3 and 23 level 4 and 5 investigations. Time intervals were ascertained from 55 papers. The median period for completion of an analytical study was 15 days (range: 4-32) for levels 4 and 5 and 31 days (range: 9-213) for level 3 investigations. Key factors influencing the speed of completing analytical studies were outbreak level, severity of infection and study design. Our findings suggest that guidance for completing analytical studies could usefully be provided, with different time intervals according to outbreak severity.


title: Confronting SARS: a view from Hong Kong.

text: Severe acute respiratory syndrome (SARS) emerged as a new disease in Guangdong Province, People's Republic of China in late 2002. Within weeks it had spread to Hong Kong and thence globally to affect over 25 countries across five continents. The disease had the propensity to cause clusters of pneumonia, particularly in healthcare workers or close family contacts. A global effort coordinated by the World Health Organization successfully defined the aetiology, epidemiology and clinical characteristics of the disease, and the implementation of case identification, isolation and infection control measures led to the interruption of the global outbreak by July 2003. The pattern of disease emergence and strategies for control of SARS provides lessons for coping with future emerging infectious disease threats.


title: The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interacts with membrane type 1 matrix metalloproteinase and CD13/aminopeptidase N and modulates their endocytic pathways.

text: The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is anchored to the cell surface via glycosylphosphatidylinositol. This molecule antagonizes the function of membrane type 1 matrix metalloproteinase (MT1-MMP) to promote proMMP-2 maturation. Here, we attempt to clarify the mechanism underlying RECK functions. First, we found that RECK forms a complex with MT1-MMP and inhibits its proteolytic activity. Notably, RECK increases the amount of MT1-MMP that associates with detergent-resistant membranes during sucrose gradient ultracentrifugation. Furthermore, perturbation of membrane cholesterol significantly affected the function of RECK in suppressing MT1-MMP function. These findings indicate that RECK possibly regulates MT1-MMP function by modulating its behavior on the cell surface as well as by enzymatic action; this prompted us to find another molecule whose behavior in detergent-resistant membranes is influenced by RECK. Subsequently, we found that RECK interacts with CD13/aminopeptidase N. Further, we found that RECK inhibits the proteolytic activity of CD13 in a cholesterol perturbation-sensitive manner. Finally, we examined whether RECK influences the behavior of MT1-MMP and CD13 during their internalization from the cell surface. In the absence of RECK, MT1-MMP and CD13 were internalized along with the markers of clathrin- or caveolae-dependent endocytosis. However, interestingly, in the presence of RECK these molecules were internalized preferentially with an endocytic marker that is neither clathrinnor caveolae-dependent, indicating that RECK modulates endocytic pathways of MT1-MMP and CD13. This modulation was correlated with the accelerated internalization and decay of MT1-MMP and CD13. This study unveils the novel function and target molecules of RECK.


title: Risk of hepatic failure in COVID-19 patients. A systematic review and meta-analysis.

text: Liver injury has been reported to occur during the disease in severe cases. Therefore, this meta-analysis study aims to investigate the incidence of liver injury among published literature from 2019-Jan-01 to 2020-April-03 to provide an outline for further studies on the liver injury of COVID-19. Four databases including Pubmed, Embase, Web of Science, and the Scopus were searched for studies published from 2019-Jan-01 to 2020-April-03. Data analysis and drawing of charts were performed using the Comprehensive Meta-Analysis Software Version 2.2 (Biostat, USA). The search yielded 450 publications, of which 64 potentially eligible studies were identified for full-text review and 21 studies fulfilling the inclusion criteria remained. A total of 4191 COVID-19 patients were included in our meta-analysis. The pooled prevalence of liver injury was 19.5% (95% CI: 14.3-26.1). According to our results, there was significant heterogeneity among the 19 studies (X2 = 738.5; p < 0.001; I2 = 94.34%). Among 288 death cases, the pooled prevalence of liver injury was 22.8% (95% CI: 11.7-39.8). In summary, the COVID-19 disease itself can result in severe and even fatal respiratory diseases and even may lead to ARDS and multiple organ failure. The results of this systematic review highlight the importance of liver injury that may assist clinicians anywhere in the globe in controlling COVID-19-related infection and complications. Moreover, the prevalence of liver injury can be higher in severe cases than in mild cases.


title: Human metapneumovirus: a new pathogen in children and adults.

text: In 2001, human metapneumovirus (hMPV) was discovered in young children with respiratory tract infection of unknown origin. In the two years since its discovery the dinical characteristics of this new virus have been darified. In children, especially those younger than one year of age, hMPV is responsible for 5 to 10% of respiratory tract infections requiring hospitalisation; its clinical course is somewhat milder, but otherwise indistinguishable from respiratory syncytial virus (RSV) infection. Human MPV can also be found in adults, in influenza-like illnesses, but also as a cause of pneumonia. Especially in the latter cases immunosuppressive conditions may be present.


title: Role of infection in chronic bronchitis.

text: Twenty-five patients with chronic bronchitis were studied intensively from 1968 to 1972. Viral, bacteriologic, mycologic, and mycoplasmal studies, both serologic and cultural, were carried out in an attempt to determine the role these agents play in exacerbations. All of the usual viral agents associated with exacerbations and 2 members of the coronavirus group, 229E and OC43, were detected. One third (33.6 per cent) of the 116 exacerbations observed could be related to viral infection or Mycoplasma pneumoniae (1 exacerbation). Viral infection was also noted to occur during periods of remission but was more commonly associated with periods of exacerbation(P less than 0.001). No interrelationship between viral and bacterial infection was apparent and neither Streptococcus pneumoniae nor Haemophilus influenzae was present more frequently in the sputum of patients in exacerbation. However, the number of S. pneumoniae organisms present in the sputum was significantly greater (P=0.04) during exacerbation than during remission and their presence was significatnly correlated with increases sputum purulence (P LESS THAN 0.01). This was not true of H. influenzae. Ampicillin was effective in clearing the sputum of S. pneumoniae but not of H. influenzae; the reverse was true of tetracycline.