title: Risk factors for extubation failure in infants with severe acute bronchiolitis.

text: OBJECTIVE To evaluate demographic characteristics, mechanical-ventilation parameters, blood gas values, and ventilatory indexes as predictors of extubation failure in infants with severe acute bronchiolitis. METHODS We conducted a prospective observational study from March 2004 to September 2005 with consecutive infants (ages 1-12 months) with severe acute bronchiolitis and considered ready to be extubated. We calculated mean airway pressure and oxygenation index. Before extubation we measured respiratory rate, tidal volume, rapid shallow breathing index, maximal inspiratory pressure, and load/force balance. Arterial blood gases were measured 1 hour before extubation. Extubation was classified as a failure if the infant needed re-intubation within 48 hours. RESULTS Extubation failure occurred in 6 (15%) of the 40 extubated infants. The respective median (and interquartile range) age, weight, and days of mechanical ventilation for the extubation-failure and extubation-success groups were: age 5 (3-8) months versus 4 (4-6) months (P = .87), weight 4 (3-5) kg versus 6 (5-7) kg (P < .001), and mechanical ventilation days 8 (6-23) d versus 6 (5-12) d (P = .52). There were no significant differences in arterial blood gas values or mechanical-ventilation parameters between the extubation-success and extubation-failure groups. There were statistically significant differences between the extubation-failure and extubation-success groups for 2 risk factors, weight <or= 4 kg and tidal volume <or= 4 mL/kg, when those risk factors had a large area under the curve of the receiver operating characteristic. Variables that had a large area under the curve were minute volume <or= 0.8 mL/kg/min and maximal inspiratory pressure <or= 50 cm H(2)O. Variables that had a small area under the curve were load/force balance >or= 5 and rapid shallow breathing index >or= 6.7. CONCLUSIONS In infants with severe acute bronchiolitis the extubation process is complex because of the combined features of this disease. Pediatric studies have not definitely determined predictive factors, weaning protocols, or ventilatory predictive indexes of extubation failure risk in infants with severe acute bronchiolitis. Lower minute volume and lower maximal inspiratory pressure had large areas under the curve of the receiver operating characteristic for extubation-failure risk in infants with severe acute bronchiolitis.


title: Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection.

text: We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-gamma-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile.


title: Antibody-mediated protection against cytotoxic T-cell escape in coronavirus-induced demyelination.

text: C57BL/6 (B6) mice infected with mouse hepatitis virus (MHV) strain JHM develop a clinically evident, demyelinating encephalomyelitis. Infectious virus can be isolated from the spinal cords of these mice and is invariably mutated in the immunodominant CD8 T-cell epitope recognized in this strain. We showed previously that these persistently infected mice did not mount a measurable serum anti-MHV neutralizing antibody response. Here we show that cytotoxic T-lymphocyte (CTL) escape was not detected in MHV-infected BALB/b mice (H-2(b) haplotype), even though the same CD8 T-cell epitopes were recognized as in B6 mice. BALB/b mice had 25-fold more MHV-specific antibody-secreting cells in the central nervous system, the site of infection, than B6 mice, suggesting that local production of anti-MHV antibody contributed to this absence of CTL escape. Additionally, administration of anti-MHV neutralizing antibody to infected B6 mice suppressed the development of CTL escape mutants. These findings indicate a key role for the anti-MHV antibody response in suppressing virus replication, thereby minimizing the emergence and competitive advantage of CTL escape mutants.


title: Replication of coronavirus MHV-A59 in sac- cells: determination of the first site of budding of progeny virions.

text: During infection of sac- cells by murine coronavirus MHV A59 the intracellular sites at which progeny virions bud correlate with the distribution of the viral glycoprotein E1. Budding is first detectable by electron microscopy at 6 to 7 hours post infection in small, smooth, perinuclear vesicles and tubules in a region transitional between the rough endoplasmic reticulum and the Golgi apparatus. At later times the rough endoplasmic reticulum becomes the major site of budding and accumulation of progeny virus particles. Indirect immunofluorescence microscopy shows that E1 is confined at 6 hours post infection to the perinuclear region while at later times it also accumulates in the endoplasmic reticulum. At 6 hours post infection the second viral glycoprotein, E2, is distributed throughout the endoplasmic reticulum and is not restricted to the site at which budding begins. Core protein, the third protein in virions, can be detected 2 hours before E1 is detectable and budding begins, and at 6 hours post infection it is distributed throughout the cytosol. We conclude that the time and the site at which the maturation of progeny virions occurs is determined by the accumulation of glycoprotein E1 in intracellular membranes. Only rarely do progeny virions bud directly into the cisternae of the Golgi apparatus but at least some already budded virions are transported to the Golgi apparatus where they occur in structures some of which also contain TPPase, a trans Golgi marker.


title: Environmental factors in the summer Olympics in historical perspective.

text: A descriptive approach is adopted in reviewing the probable impact of environmental factors during the summer Olympic Games since their inception in 1896. A historical analytical perspective is impractical due to the lack of reliable climatic data for the earlier Games and the evolution of a myriad of factors that impinge on competitive performance at elite level. Nevertheless, the endurance running events, particularly the marathon, are considered in detail with respect to exposure to environmental forces. Heat, humidity, air pollution, altitude and the geographical features of the race course are considered selectively and dealt with in order of chronology and global climatic zones. We focus on diverse climate zones and particular environmental conditions in order to scrutinize their likely influences on competitive performance, especially in the Olympic marathon races. Notwithstanding the limitations of a narrative approach, performances are related to particular weather data and mitigating influences. Travel difficulties are addressed where these affected a majority of competitors. Environmental stress was associated with the ill-timing and poor organization of the earlier Games. While many of these detrimental and injurious features have been alleviated since then, other environmental stress factors are less prone to mitigation and thus remain a sometimes severe challenge to endurance races. The unique environment conditions for outdoor endurance races in temperate climate zones tend to be highly variable and therefore difficult to predict.


title: Structure of the uncleaved ectodomain of the paramyxovirus (hPIV3) fusion protein.

text: Class I viral fusion proteins share common mechanistic and structural features but little sequence similarity. Structural insights into the protein conformational changes associated with membrane fusion are based largely on studies of the influenza virus hemagglutinin in pre- and postfusion conformations. Here, we present the crystal structure of the secreted, uncleaved ectodomain of the paramyxovirus, human parainfluenza virus 3 fusion (F) protein, a member of the class I viral fusion protein group. The secreted human parainfluenza virus 3 F forms a trimer with distinct head, neck, and stalk regions. Unexpectedly, the structure reveals a six-helix bundle associated with the postfusion form of F, suggesting that the anchor-minus ectodomain adopts a conformation largely similar to the postfusion state. The transmembrane anchor domains of F may therefore profoundly influence the folding energetics that establish and maintain a metastable, prefusion state.


docid: mgsidgyt

title: Detection of infectious bronchitis virus and specific anti- viral antibodies using a Concanavalin A-Sandwich-ELISA.

text: Concanavalin A-Sandwich ELISA (Con A-S-ELISA) was developed for the detection of infectious bronchitis virus (IBV) or chicken specific anti-viral antibodies. The antigen detection limit for the Con A-S-ELISA was 10(5,1) EID(50)/mL. Three homologous and four heterologous IBV strains were similarly detected. This assay was highly effective in detecting the virus after infected tissue homogenates were passed once in embryonated chicken eggs, showing a good agreement with virus isolation technique. The Con A-S-ELISA was also used to measure anti-IBV chicken antibodies and showed a high coefficient of correlation (r = 0.85) and an agreement of k = 0.80 with the commercially available Indirect-ELISA. The relative sensitivity and specificity between these two tests were, respectively, 92.86% and 95.65% with an accuracy of 93.39%. Thus, the Con A-S-ELISA proved to be able to detect alternatively homologous and heterologous IBV strains or specific chicken anti- IBV antibodies, using the Con A as capture reagent of this assay.


COVID-19 Pandemic: Are There Unique Cutaneous Manifestations in Patients Infected With SARS-CoV-2?


title: Use of over-the-counter medications in prevention and treatment of upper respiratory tract infections.

text: Over-the-counter (OTC) medications are a fast developing branch of the pharmaceutical industry, in both Poland and rest of the world. The aim of the work was to evaluate the factors that influence the purchase and use of OTC medications in prevention and treatment of upper respiratory tract infections. The analysis involved 450 randomly chosen subjects, aged 19-80. The study was performed using a questionnaire which included a number of questions related to the characteristics of respondents such as: health, socio-demographic data, and factors influencing the purchase of OTC medications used in respiratory tract infections. The self-medication phenomenon in upper respiratory tract infections is significant in Poland and will continue to increase with support of many demographic and socio-economic factors. Despite certain health risks resulting from the inappropriate use of OTC medications, it should continue to be offered as a part of the pharmaceutical market.


Polymicrobial infection in enteritis.


title: Field validation of a commercial blocking ELISA to differentiate antibody to transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus and to identify TGEV-infected swine herds.

text: A commercially available blocking ELISA was analyzed for its ability to identify antibodies to porcine coronaviruses (transmissible gastroenteritis virus [TGEV] or porcine respiratory coronavirus [PRCV]), to differentiate antibodies to TGEV and PRCV, and to identify TGEV-infected herds. Nine sera from uninfected pigs, 34 sera from 16 pigs experimentally infected with TGEV, and sera from 10 pigs experimentally infected with PRCV were evaluated using both the TGEV/PRCV blocking ELISA and a virus neutralization (VN) assay. The ELISA was not consistently effective in identifying pigs experimentally infected with TGEV until 21 days postinfection. Sera from 100 commercial swine herds (1,783 sera; median 15 per herd) were similarly evaluated using both tests. Thirty of these commercial herds had a clinical history of TGEV infection and a positive TGEV fluorescent antibody test recorded at necropsy within the last 35 months, while 70 herds had no history of clinical TGEV infection. The blocking ELISA and the VN showed good agreement (kappa 0.84) for the detection of porcine coronavirus antibody (TGEV or PRCV). The sensitivity (0.933) of the ELISA to identify TGEV-infected herds was good when considered on a herd basis. The ELISA was also highly specific (0.943) for the detection of TGEV-infected herds when the test results were evaluated on a herd basis. When sera from specific age groups were compared, the ELISA identified a greater proportion (0.83) of pigs in herds with TGEV antibody when suckling piglets were used. In repeatability experiments, the ELISA gave consistent results when the same sera were evaluated on different days (kappa 0.889) and when sera were evaluated before and after heating (kappa 0.888). The blocking ELISA was determined to be useful for herd monitoring programs and could be used alone without parallel use of the VN assay for the assessment of large swine populations for the detection of TGEV-infected herds.


title: A preparative purification process for recombinant hepatitis B core antigen using online capture by expanded bed adsorption followed by size-exclusion chromatography.

text: Hepatitis B core antigen (HBcAg) is an important serological marker used in the diagnosis of hepatitis B virus (HBV) infections. In the current study, a fast and efficient preparative purification protocol for truncated HBcAg from Escherichia coli disruptate was developed. The recombinant HBcAg was first captured by anion exchange expanded bed adsorption chromatography integrated with a cell disruption process. This online capture process has shortened the process time and eliminated the "hold-up" period that may be detrimental to the quality of target protein. The eluted product from the expanded bed adsorption chromatography was subsequently purified using size-exclusion chromatography. The results showed that this novel purification protocol achieved a recovery yield of 45.1% with a product purity of 88.2%, which corresponds to a purification factor of 4.5. The recovered HBcAg is still biologically active as shown by ELISA test.


title: Adaptation to natural facial categories.

text: Face perception is fundamentally important for judging the characteristics of individuals, such as identification of their gender, age, ethnicity or expression. We asked how the perception of these characteristics is influenced by the set of faces that observers are exposed to. Previous studies have shown that the appearance of a face can be biased strongly after viewing an altered image of the face, and have suggested that these after-effects reflect response changes in the neural mechanisms underlying object or face perception. Here we show that these adaptation effects are pronounced for natural variations in faces and for natural categorical judgements about faces. This suggests that adaptation may routinely influence face perception in normal viewing, and could have an important role in calibrating properties of face perception according to the subset of faces populating an individual's environment.


title: Update: severe acute respiratory syndrome--United States, May 14, 2003.

text: CDC continues to work with state and local health departments, the World Health Organization (WHO), and other partners to investigate cases of severe acute respiratory syndrome (SARS). This report provides an update on reported SARS cases worldwide and in the United States.


title: Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation.

text: RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.


title: Extensive bilateral vertebral artery remodeling following treatment of dissection using pipeline embolic device.

text: BACKGROUND Cerebral artery dissection remains a significant cause of stroke, and the mainstay of treatment has been medical management with anticoagulation, although flow-diverting stents have been used in some cases of arterial dissection resistant to medical management. METHODS We present a case report of bilateral vertebral artery stenting using pipeline embolic device flow-diverting stents, after failed medical management of the dissection. RESULTS This case demonstrated substantial subsequent vertebral arterial remodeling and good clinical outcome with maintenance of posterior circulation. The patient did not suffer any further strokes or posterior circulation symptoms following vertebral artery remodeling. CONCLUSION In cases where traditional management of arterial dissection has not been efficacious, flow-diverting stents may be useful in treating dissections of the posterior cerebral circulation, even with bilateral involvement.


title: Serum hepatic enzyme manifestations in patients with severe acute respiratory syndrome: retrospective analysis.

text: AIM To evaluate the hepatic function in patients with severe acute respiratory syndrome (SARS) and possible causes of hepatic disorder in these patients. METHODS One hundred and eighty-two patients with SARS were employed in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) were analyzed in these patients. Patients with different hospital treatments were further investigated. RESULTS Of the 182 patients, 128(70.3%) had abnormal ALT activity, 57(31.3%) had abnormal AST activity and 87(47.8%) had abnormal LDH activity. The peak of elevated hepatic enzyme activities occurred between the sixth day and the tenth day after the first day of reported fever. Of the 182 patients, 160(87.9%) had been treated with antibiotics, 137(75.2%) with Ribavirin, and 115(63.2%) with methylpredisolone. There was no statistically significant correlation between the duration of Ribavirin treatment and hepatic dysfunction. CONCLUSION Abnormal liver functions were common in patients with SARS and could be associated with virus replication in the liver.


title: Human metapneumovirus as a major cause of human respiratory tract disease.

text: BACKGROUND Human metapneumovirus (hMPV) is a newly identified paramyxovirus that appears to be one of the most significant and common viral infections in humans. The virus, first isolated in 2001, is a clear cause of lower respiratory tract disease in both the very young and the frail elderly. The virus causes acute wheezing in children or, less commonly, croup or pneumonia. METHODS/RESULTS Molecular epidemiology studies have shown that field strains exhibit sufficient sequence diversity to designate 2 subgroups of circulating viruses. Small animal and nonhuman primate models of infection have been described, which will allow studies of pathogenesis and immunity. Recombinant viruses have already been generated by several groups using reverse genetics, which facilitates the study of the biology of the virus and the generation of live attenuated vaccine candidates. CONCLUSIONS Ongoing research promises to elucidate the molecular basis for pathogenesis and immunity of human metapneumovirus infections and to pave the way for rapid vaccine development.


Telling the story of SARS: compassionate oncology care in the face of a futuristic health crisis.


title: Marginal sinus fistula supplied exclusively by vertebral artery feeders.

text: A 54-year-old woman is reported with severe pulsatile tinnitus. Digital subtraction angiography demonstrated dural arteriovenous fistula of the marginal sinus with feeders arising exclusively from bilateral vertebral arteries. Patient underwent successful transarterial Onyx embolization with complete angiographic and clinical cure.


title: Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry.

text: Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. In this study, we used cell culture-produced infectious HCV to analyze the viral entry pathway into Huh-7.5 cells. Bafilomycin A1 and concanamycin A, inhibitors of vacuolar ATPases, prevented HCV entry when they were present prior to infection and had minimal effect on downstream replication events. HCV entry therefore appears to be pH dependent, requiring an acidified intracellular compartment. For many other enveloped viruses, acidic pH triggers an irreversible conformational change, which promotes virion-endosomal membrane fusion. Such viruses are often inactivated by low pH. In the case of HCV, exposure of virions to acidic pH followed by return to neutral pH did not affect their infectivity. This parallels the observation made for the related pestivirus bovine viral diarrhea virus. Low pH could activate the entry of cell surface-bound HCV but only after prolonged incubation at 37 degrees C. This suggests that there are rate-limiting, postbinding events that are needed to render HCV competent for low-pH-triggered entry. Such events may involve interaction with a cellular coreceptor or other factors but do not require cathepsins B and L, late endosomal proteases that activate Ebola virus and reovirus for entry.


title: Comparison of serologic techniques for the detection of antibodies against feline coronaviruses.

text: The seroprevalence of feline coronavirus (FCoV) antibodies was studied in cats in southern Italy. One hundred twenty sera collected from cats belonging to catteries or community shelters and to households were tested for FCoV type I and II antibodies. The virus neutralization (VN) was performed and compared with indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). Ninety-six sera tested positive for FCoV antibodies by VN and ELISA. Interestingly, ELISA revealed 2 more positive sera than did the VN test and 3 more positive sera than did the IFAT. All results were confirmed by Western blotting. ELISA proved to be more sensitive and detected a seroprevalence of about 82%. Considering the cross-reactivity of FCoV type I and type II, ELISA was able to detect antibodies against both serotypes, allowing the use of the assay as a reference test for sera screening. The high prevalence of antibodies observed indicates that FCoVs are common in southern Italian cat populations.


title: Reduced incorporation of SARS-CoV spike protein into viral particles due to amino acid substitutions within the receptor binding domain.

text: Cell clone #21 is a long-term producer of the infectious SARS-coronavirus, although the incorporation rate of spike (S) protein into virions is significantly lower. Sequencing analysis of the viral structural proteins revealed four and one amino acid substitutions in the S and membrane (M) proteins, respectively. We demonstrated, using a viral-like particle formation system, that the S mutations were involved in the lower incorporation of the S protein into virions, although the M mutation that disrupts the glycosylation was not present in this phenotype. Further mutational experiments identified two substitutions, Y442C and L472F, within the receptor binding domain that could be critical for the reduced S incorporation, as well as reduced binding affinity between the S protein and ACE2 receptor. Thus, these two amino acid substitutions might lead to a conformational change in the S protein, resulting in reduced incorporation into viral particles.


title: Prolonged motor block following epidural anaesthesia: A proposed pathway for investigation and management to facilitate rapid MRI scanning to exclude vertebral canal haematoma.

text: Vertebral canal haematoma following epidural anaesthesia is a rare but potentially devastating occurence, which can lead to permanent neurological damage. Early clinical identification and diagnosis using MRI imaging with surgical decompression of the haematoma can lead to full recovery (Kebaish 2004). However surgical patients often have metal clips or staples, which are left inside the body, some of which are not MRI compatible. Currently there is no process to document which surgical clips have been used and their MRI compatibility in an accessible format. This can lead to a delay in performing MRI imaging. We propose a clinical pathway to expedite diagnosis of vertebral canal haematoma to incorporate a system to allow rapid identification of MRI compatibility of surgical clips used during surgery.


title: Catheter Related Right Atrial Thrombus in Patients on Maintenance Hemodialysis: Results of a Single Centre Retrospective Study from a Tertiary Care Hospital.

text: Objective To study the magnitude of the complication of catheter associated right atrial thrombus (CRAT) in patients with tunnelled central venous hemodialysis catheters (THC) for maintenance hemodialysis (MHD). Material and methods A retrospective study was conducted among patients with end stage kidney disease (ESKD) with THC for MHD who had undergone screening for CRAT with a 2D-echo (2DE) just before removal of the THC. The occurrence of CRAT and other clinical parameters were documented in these patients. Results A total of 28 patients (mean [SD] age 51 [15.2] years; females 17 [60.7%]) were included in the study. CRAT was observed in 5 (17.9%) patients. There was no difference in mean age in patients with or without thrombus (48±13.02 vs 51.61 ± 15.78 years; p = 0.61). History of diabetes and hypertension was present in 2 and all 5 patients respectively. There was no significant difference in the period the THC was in place in patients with or without CRAT (13±7.8 months vs 10.57±5.66 months; p = 0.54). There was no association between catheter related blood stream infection (CRBSI) and CRAT (p= 0.29). Conclusion The incidence of CRAT in patients with THC for MHD was 17.9%. Patients with THC for MHD should be examined for presence of CRAT before removal of THC to prevent fatal pulmonary thromboembolism.


title: Push-Ups vs. Bench Press Differences in Repetitions and Muscle Activation between Sexes.

text: Push-ups are an ubiquitous resistance training exercise. While exhibiting a relatively similar upper body motion to the bench press, there are substantial differences in repetitions when employing similar relative loads. The objective was to examine sex-related differences in repetitions and muscle activation associated with push-ups and bench press exercises. Twenty resistance-trained participants (10 men [22 ± 6.1 years] and 10 [24 ± 5.7 years] women) performed maximum push-up and bench press repetitions with loads relative to the body mass during a push-up. Electromyographic (EMG) electrodes were positioned on the middle and anterior deltoids, triceps and biceps brachii, and pectoralis major muscles and their relative (normalized to a maximum voluntary contraction) activity was compared between the two exercises performed to task failure. Both females (3.5 ± 3.9 vs.15.5 ± 8.0 repetitions; p = 0.0008) and males (12.0 ± 6.3 vs. 25.6 ± 5.2 repetitions; p < 0.0001) performed 77.4% and 53.1% less bench press than push-up repetitions respectively. Males significantly exceeded females with both push-ups (p = 0.01) and bench press (p = 0.004) repetitions. Significant linear regression equations were found for females (r2 = 0.55; p = 0.03), and males (r2 = 0.66; p < 0.0001) indicating that bench press repetitions increased 0.36 and 0.97 for each push-up repetition for females and males respectively. Triceps (p = 0.002) and biceps brachii (p = 0.03) EMG mean amplitude was significantly lower during the push-up concentric phase, while the anterior deltoid (p = 0.03) exhibited less activity during the bench press eccentric phase. The sex disparity in repetitions during these exercises indicates that a push-up provides a greater challenge for women than men and regression equations may be helpful for both sexes when formulating training programs.


title: Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.

text: A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10 000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs.


title: [Side effects of glucocorticosteroids in the management of 1291 patients of SARS].

text: OBJECTIVE To analysis the relationship between glucocorticosteroids (GCS) usage and side effects in the treatment of severe acute respiratory syndrome (SARS). METHODS All clinical records of probable SARS patients in Beijing were collected and input into an Epi6 database, in which 1 291 patients had entire information and met the clinical criteria of SARS. The usage of GCS and GCS associated side effects were analyzed retrospectively. RESULTS Patients accepted GCS therapy were 83.96% (n=1 084), whereas 16.04%(n=207) did not take GCS. The average dosage of GCS was 160 mg/d in the first week, and then reduced to 80 mg/d and 40 mg/d in the second and the third weeks, respectively. Initial blood glucose, systolic pressure (SBP), and diastolic pressure (DBP) were no significant difference between GCS group and non-GCS group. The highest blood glucose during the treatment in GCS group was markedly higher than that in non-GCS group [(8.68+/-4.80) mmol/L vs (6.39+/-3.71) mmol/L, P<0.05)]. The highest blood glucose and average blood glucose after initiation of GCS therapy were elevated in GCS group. The levels of blood glucose were correlated with the initial, maximum, and cumulative GCS dosages. Average blood glucose was increased markedly in groups with MP(Initial) > or =80 mg/d (Methyprednisonlone), MP(Maximal) > or =160 mg/d, or MP(Cumulative) > or = 3000 mg. The blood glucose grew up significantly in the first and the second weeks in the treatment with GCS, and then returned to normal level gradually. Hyperglycemia duration in the group with MP(Cumulative) > or =3000 mg persisted longer than that in the other groups (P< 0.05). The lowest serum potassium during the treatment and the duration of hypokalemia in GCS group were significantly different from that in non-GCS group [(3.66+/-0.50) mmol/L vs (4.01+/-0.51) mmol/L, P< 0.001 ;1(1, 75) days vs 1(1, 9) days, P<0.05, respectively]. Average serum potassium and the duration of hypokalemia were related to the dosages of GCS. Serum potassium reached its nadir in the first week of GCS treatment and then grew up in the second week. In groups with MP(Initial) > or =320 mg/d, MP(Maximal) > or =320 mg/d, and MP(Cumulative) > or =3000 mg, the level of serum potassium was lower and the duration of hypokalemia was longer than that in other groups. They began to returned to normal level in the third week. Administration of GCS prolonged the time of hypocalcemia[19 (1, 74) days in GCS group vs 8 (1, 32) days in non-GCS group, P< 0.05]. The duration of hypocalcemia was prolonged according to the increasing of the maximal or the cumulative dosage of GCS. However, the duration of hypocalcemia in group with MP(Cumulative) <999 mg was similar to that in non-GCS group (P > 0.05). After GCS administration, SBP and DBP were increased gradually, and reached their peaks in the fourth week [SBP(117.2+/-14.0) mm Hg and DBP (72.5+/-9.1) mm Hg vs SBP (120.0+/-12.5) mm Hg and DBP (74.5+/-8.7) mm Hg, P< 0.05, 1 mm Hg=0.133 kPa]. CONCLUSION Hyperglycemia and hypokalemia are correlated with GCS dosage and duration. Administration with GCS influences SBP, DBP, and duration of hypocalcemia. Appropriate low dosage of GCS (MP(Initial) and MP(Maximal) < 159 mg/d, MP(Cumulative)< 2999 mg) causes few changes of blood glucose, serum potassium, and blood calcium. It is important to monitor laboratory findings during the treatment with GCS.


title: Single-incision laparoscopic distal pancreatectomy.

text: Single-incision laparoscopic surgery (SILS) is a novel area of minimally invasive surgery, and rapidly evolving in the field of abdominal surgery. However, SILS is not a common procedure for pancreatic surgery. We describe our first experience with a SILS approach in a patient with a metastatic pancreatic tumor. We performed a SILS distal pancreatectomy (SILS-DP) using 3 trocars placed through a single port at an umbilical incision. In our case, the most important surgical technique was the stomach-hanging method to obtain a favorable laparoscopic view of the pancreas. Although SILS-DP is a safe and feasible procedure, further studies are required to determine the advantages of this procedure in comparison with the standard laparoscopic method.


Shaping the future of global health.


Q&A with Albert S. Woo, MD Forging a New Frontier in 3D Printing during COVID-19 Pandemic.


Pathogenesis of rhinovirus common colds in human voluteers.


title: Outbreak of febrile respiratory illness caused by adenovirus at a South Korean military training facility: clinical and radiological characteristics of adenovirus pneumonia.

text: Adenovirus often causes respiratory disease outbreaks in military training soldiers. Compared with adenovirus pneumonia in young military adults, symptoms arising from febrile respiratory illness (FRI) caused by adenovirus have not been previously evaluated in Korean soldiers. We conducted an event-based outbreak investigation involving 712 male soldiers aged 19 to 21 years from March 14 to 30, 2012 to evaluate the epidemiological and clinical characteristics of patients with pneumonia and FRI caused by adenovirus. We described the laboratory and radiological characteristics of patients with adenovirus pneumonia. Among these, 407 cases of FRI and 15 cases of pneumonia were identified through active surveillance (attack rate of FRI, 57.16%; attack rate of pneumonia, 2.11%). Fire training and march training may present environmental risk factors for adenovirus-associated outbreaks. Most symptoms were mild. The most frequent symptom in patients with pneumonia and FRI was cough. Patients with pneumonia were associated with an increased incidence of dizziness (crude odds ratio [cOR], 9.65; 95% confidence interval [CI], 2.38-37.15) and a decreased incidence of rhinorrhea (cOR, 0.15; 95% CI, 0.04-0.53) during adenovirus-associated outbreaks. Differential leukocyte count revealed high monocytes, low lymphocytes, and low eosinophils, and chest computed tomography revealed a consolidation pattern and right lobar pneumonia. These findings warrant a high level of suspicion for adenovirus pneumonia.


Polypeptide structure of bovine enteritic coronavirus: comparison between a wild strain purified from feces and a HRT 18 cell adapted strain.


title: A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

text: The coronavirus main protease, M(pro), is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M(pro) inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M(pro) inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K(i) value of 35.3 muM. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.


title: Bioinformatics research on the SARS coronavirus (SARS_CoV) in China.

text: Severe acute respiratory syndrome (SARS) first appeared in 2002 in China, which fastly affected about 8000 patients over 29 countries and caused 774 fatalities. As its pathogen was identified as a new kind of coronavirus (SARS_CoV), its genome was quickly sequenced on several isolates. Studies on its functional genomics were performed by combinatorial application of all the available bioinformatics tools and the development of new programs. In this way, it was found that the four proteins were absolutely responsible for nosogenesis of SARS, i.e. spike (S) protein; small envelop (E) protein; membrane (M) protein; and nucleocaspid (N) protein. Molecular evolution studies have revealed that SARS must be originated from wild animals, and it was demonstrated that the major genetic variations in some critical genes, particularly the Spike gene, was essential for the transition from animal-to-human transmission to human-to-human transmission. Theoretical models, either Logistic model or SIR model, were developed to describe the transmission of SARS. The recorded difference of SARS spreading in Beijing and Hong Kong was also reasonably analyzed according to these models. The whole process of fruitful bioinformatics studies, along with other related scientific investigations have set up an unprecedented paradigm for human of how to battle against sudden-breaking and catastrophic epidemics.


title: Preparing for avian influenza.

text: PURPOSE OF REVIEW Pandemic influenza is inevitable, will have significant impact on the population and will challenge healthcare delivery. Planning for an influenza pandemic will improve the ability of healthcare facilities to respond successfully. RECENT FINDINGS Planning activities involve determining the role of the facility during an influenza pandemic, estimating resources necessary to fulfil this role and developing the infrastructure, material and human resources surge capacity necessary to meet the estimated needs. Plans to perform surveillance for potentially contagious individuals, handle clinical specimens, increase social distancing during a pandemic and the development of personal preparedness plans may be beneficial. SUMMARY The goal of this review is to provide a framework for healthcare facility pandemic influenza planning.


title: Colocalization and interaction of the porcine arterivirus nucleocapsid protein with the small nucleolar RNA-associated protein fibrillarin.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleus and nucleolus. The mechanism of nuclear translocation and whether N associates with particular nucleolar components are unknown. In the present study, we show by confocal microscopy that the PRRSV N protein colocalizes with the small nucleolar RNA (snoRNA)-associated protein fibrillarin. Direct and specific interaction of N with fibrillarin was demonstrated in vivo by the mammalian two-hybrid assay in cells cotransfected with the N and fibrillarin genes and in vitro by the glutathione S-transferase pull-down assay using the expressed fibrillarin protein. Using a series of deletion mutants, the interactive domain of N with fibrillarin was mapped to a region of amino acids 30 to 37. For fibrillarin, the first 80 amino acids, which contain the glycine-arginine-rich region (the GAR domain), was determined to be the domain interactive with N. The N protein was able to bind to the full-length genomic RNA of PRRSV, and the RNA binding domain was identified as the region overlapping with the nuclear localization signal situated at positions 41 to 47. These results suggest that the N protein nuclear transport may be controlled by the binding of RNA to N. The PRRSV N protein was also able to bind to both 28S and 18S ribosomal RNAs. The protein-protein interaction between N and fibrillarin was RNA dependent but independent of N protein phosphorylation. Taken together, our studies demonstrate a specific interaction of the PRRSV nucleocapsid protein with the host cell protein fibrillarin in the nucleolus, and they imply a potential linkage of viral strategies for the modulation of host cell functions, possibly through rRNA precursor processing and ribosome biogenesis.


The role of public health and occupational physicians in the new millennium.


title: Feline immunodeficiency virus infection in a population of pet cats from southeastern Florida.

text: Blood samples from 95 randomly selected pet cats that were brought to veterinarians in southeastern Florida were tested for antibodies to feline immunodeficiency virus (FIV). Virus-specific antibodies (indicative of virus infection) were found in 8 of the 95 (8.4%) cats tested. All of the virus-infected cats were males (statistically significant, P less than or equal to 0.016) and were at least 1 year of age. The 3 most severely ill cats infected with FIV were also infected with feline leukemia virus.


title: Outbreak of necrotizing enterocolitis associated with Enterobacter sakazakii in powdered milk formula.

text: We describe an outbreak of necrotizing enterocolitis (NEC) that occurred in the neonatal intensive care unit of our hospital. A total of 12 neonates developed NEC in June-July 1998. For two of them, twin brothers, the NEC turned out to be fatal. Enterobacter sakazakii, a known contaminant of powdered milk formula, was isolated from a stomach aspirate, anal swab, and/or blood sample for 6 of the 12 neonates. A review of feeding procedures revealed that 10 of the 12 patients were fed orally with the same brand of powdered milk formula. E. sakazakii was isolated from the implicated prepared formula milk as well as from several unopened cans of a single batch. Molecular typing by arbitrarily primed PCR (AP-PCR) confirmed, although partially, strain similarity between milk and patient isolates. No further cases of NEC were observed after the use of the contaminated milk formula was stopped. With this outbreak we show that intrinsic microbiological contamination of powdered milk formula can be a possible contributive factor in the development of NEC, a condition encountered almost exclusively in formula-fed premature infants. The use of sterilized liquid milk formula in neonatal care could prevent problems with intrinsic and extrinsic contamination of powdered milk formula.


title: Human metapneumovirus: a ubiquitous and long-standing respiratory pathogen.

text: BACKGROUND Human metapneumovirus (hMPV) is a recently described human pathogen first identified in respiratory specimens of young children suffering from respiratory syndromes ranging from mild to severe. METHODS AND RESULTS Virological studies have reported the presence of hMPV infections in many countries from all continents. Seroprevalence studies have indicated that the virus has been circulating in humans for more than 50 years and that it infects virtually all children by the ages of 5-10 years. In young children, hMPV has been mainly associated with bronchiolitis but also with pneumonitis, otitis media and acute exacerbation of asthma. The contribution of hMPV in respiratory syndromes of adults has been studied considerably less; initial studies have indicated a role for this pathogen in flu-like syndromes and in significant percentages of chronic obstructive pulmonary disease exacerbations and cases of community-acquired pneumonia during the winter-spring period. Both primate and rodent experimental models have been used to characterize the pathogenesis of this respiratory virus. In some of these models, intranasal hMPV inoculation has elicited not only important viral replication but also significant pulmonary inflammation and clinical disease. Recently a few groups have developed reverse genetic systems for hMPV, allowing a better understanding of viral pathogenesis and generation of attenuated viral strains for immunization. CONCLUSIONS Recent studies on hMPV have provided a better understanding of the epidemiology and pathogenesis associated with this viral infection, and have enhanced the prospect of developing efficient therapeutic agents and vaccine candidates.


title: [Evaluation of tracheal intubation in critical SARS patients].

text: OBJECTIVE To analyze tracheal intubation and respiratory treatment in the critical severe acute respiratory syndrome (SARS) patients. METHODS Review and analyze tracheal intubation and respiratory treatment in critical SARS patients in intensive care unit (ICU). RESULTS Three of thirteen patients had been intubated or received tracheotomy before they entered into ICU, the other patients received treatment of nasal cannula or oxygen mask. With the development of the disease, two patients had been intubated because of respiratory failure or tracheotomy. Tracheal intubation was twice made in two patients in order to replace tracheal tubes. CONCLUSIONS The patient should be intubated or received tracheotomy if non-invasive respiratory support has no effect. Standard protection could protect medical staff from infection under tracheal intubation.


title: Confronting zoonoses through closer collaboration between medicine and veterinary medicine (as 'one medicine').

text: In the 19th century, the concept of 'one medicine' was embraced by leaders in the medical and veterinary medical communities. In the 20th century, collaborative efforts between medicine and veterinary medicine diminished considerably. While there have been some notable exceptions, such as Calvin W. Schwabe's proposal for unifying human and veterinary medicine and joint efforts by the Food and Agriculture Organization and World Health Organization to control zoonotic diseases, 'one medicine' has languished in the modern milieu of clinical care, public health, and biomedical research. Risks of zoonotic disease transmission are rarely discussed in clinical care which is of particular concern if humans and/or animals are immunosuppressed. Physicians and veterinarians should advise their patients and pet-owning clients that some animals should not be pets. The risk of zoonotic disease acquisition can be considerable in the occupational setting. Collaborative efforts in biomedical research could do much to improve human and animal health. As the threat of zoonotic diseases continues to increase in the 21st century, medicine and veterinary medicine must revive 'one medicine' in order to adequately address these challenges. 'One medicine' revival strategies must involve medical and veterinary medical education, clinical care, public health and biomedical research.


title: Laryngeal Mask Airway and Valsalva Maneuver During Ophthalmic Surgery: A Case Report.

text: The use of a supraglottic airway, also called laryngeal mask airway (LMA), is gaining in popularity for delivery of general anesthesia in certain situations and is shown to be safe. Use of infraglottic airways (tracheal tubes) allows for positive pressure ventilation and maneuvers, such as holding continuous positive pressure in the airway to check for pleural and dural leaks. We describe the successful use of the LMA (Teleflex Inc) for general anesthesia, in which continuous positive airway pressure of 15 cm H2O held for 20 seconds allowed the neurosurgeon to identify the site of a cerebrospinal fluid (CSF) leak and successfully repair the leak. A well-seated LMA can be successfully used to produce continuous positive pressure in the airway not exceeding 20 cm H2O for 20 seconds to facilitate surgical identification of CSF leaks.


title: Neutralizing antibodies against feline herpesvirus type 1 in captive wild felids of Brazil.

text: Feline herpesvirus type 1 infection affects domestic cats, causing mainly upper respiratory tract diseases. Although this infection has been described in captive and free-ranging wild felids from Europe, Asia, North America, and Africa, no information is available on its occurrence among wild felids of Brazil. In this study, 250 serum samples of six species of Brazilian captive wild felids (Leopardus tigrinus, Leopardus wiedii, Herpailurus yaguarondi, Puma concolor, Leopardus pardalis, and Panthera onca) were examined for neutralizing antibodies to feline herpesvirus type 1. Positive sera were found in 72% of L. tigrinus samples, 15% of L. wiedii, 6% of L. pardalis, 8% of H. yaguarondi, 18% of P. concolor, and 14% of P. onca. The relatively low percentages of seropositivity and low antibody titers found among the last five species suggest that feline herpesvirus type 1 does not circulate extensively among these animals. Nevertheless, quarantine, serologic screening, and vaccination of newly introduced felids is recommended in zoos in order to prevent virus transmission and outbreaks of the disease among wild felids kept in captivity.


title: Thick lung wedge resection for acute life-threatening massive hemoptysis due to aortobronchial fistula.

text: Massive hemoptysis from an aortobronchial fistula due to thoracic aortic dissection is an extremely rare symptom, but is a potentially life-threatening condition. We report a case of acute massive hemoptysis due to aortobronchial fistula that was successfully controlled by a simple and rapid thick wedge resection of the lung with hematoma by using the black cartilage stapler. A 65-year-old man was admitted to our hospital with acute massive hemoptysis. After tracheal intubation, chest computed tomography revealed hematoma in the left lung and ruptured aortic dissection from the distal arch to the descending aorta. He was diagnosed with aortobronchial fistula and underwent an emergency surgery on the same day. We performed posterolateral thoracotomy. A dissecting aortic aneurysm (diameter, ~80 mm) with adhesion of the left upper lobe and the superior segment of the lower lobe was found. The lung parenchyma expanded with the hematoma. We stapled the upper and lower lobes by using the black cartridge stapler along the aortopulmonary window. Massive hemoptysis disappeared, and the complete aortic dissection appeared. Aortic dissection with adherent lung was excised, and graft replacement of the distal arch and descending thoracic aorta was performed. Proximal lung wedge resection using black cartridge stapler is a simple and quick method to control massive hemoptysis from aortic dissection; hence, this procedure is an effective option to control massive hemoptysis due to aortobronchial fistula. This technique could rapidly stop massive hemoptysis and prevent dissection of the adherent lung tissue and intra-thoracic bleeding.


title: Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes.

text: Upon local delivery, adenovirus (Ad) serotype 5 viruses use the coxsackie and Ad receptor (CAR) for cell binding and alpha(v) integrins for internalization. When administered systemically, however, their role in liver tropism is limited because CAR-permissive and mutated viruses show similar biodistribution, a finding recently attributed to blood coagulation factor (F) IX or complement protein C4BP binding to the adenovirus fiber and "bridging" to either low-density lipoprotein receptor-related protein or heparan sulfate proteoglycans. Here, we show that hepatocyte transduction in vitro can be enhanced by the vitamin K-dependent factors FX, protein C, and FVII in addition to FIX but not by prothrombin (FII), FXI, and FXII. This phenomenon was not dependent on proteolytic activation or cell signaling activity and for FX was mediated by direct virus-factor binding. Human FX substantially enhanced hepatocyte transduction by CAR-permissive and mutated viruses in an ex vivo liver perfusion model. In vivo, global down-regulation of vitamin K-dependent zymogens by warfarin significantly diminished liver uptake of CAR-deleted Ads; however, this phenomenon was fully rescued by acute infusion of human FX. Our results indicate a common and pivotal role for distinct vitamin K-dependent coagulation factors in mediating hepatocyte transduction by adenoviruses in vitro and in vivo.


title: Design of multichannel functional near-infrared spectroscopy system with application to propofol and sevoflurane anesthesia monitoring.

text: Monitoring the changes of cerebral hemodynamics and the state of consciousness during general anesthesia (GA) is clinically important. There is a great need for developing advanced detectors to investigate the physiological processes of the brain during GA. We developed a multichanneled, functional near-infrared spectroscopy (fNIRS) system device and applied it to GA operation monitoring. The cerebral hemodynamic data from the forehead of 11 patients undergoing propofol and sevoflurane anesthesia were analyzed. The concentration changes of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin, and cerebral tissue heart rate were determined from the raw optical information based on the discrete stationary wavelet transform. This custom-made device provides an easy-to-build solution for continuous wave-fNIRS system, with customized specifications. The developed device has a potential value in cerebral monitoring in clinical settings.


title: Understanding helicases as a means of virus control.

text: Helicases are promising antiviral drug targets because their enzymatic activities are essential for viral genome replication, transcription, and translation. Numerous potent inhibitors of helicases encoded by herpes simplex virus, severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, West Nile virus, and human papillomavirus have been recently reported in the scientific literature. Some inhibitors have also been shown to decrease viral replication in cell culture and animal models. This review discusses recent progress in understanding the structure and function of viral helicases to help clarify how these potential antiviral compounds function and to facilitate the design of better inhibitors. The above helicases and all related viral proteins are classified here based on their evolutionary and functional similarities, and the key mechanistic features of each group are noted. All helicases share a common motor function fueled by ATP hydrolysis, but differ in exactly how the motor moves the protein and its cargo on a nucleic acid chain. The helicase inhibitors discussed here influence rates of helicase-catalyzed DNA (or RNA) unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid release, or by disrupting the interaction of a helicase with a required cofactor.


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title: Management of Fever in Infants and Young Children.

text: Despite dramatic reductions in the rates of bacteremia and meningitis since the 1980s, febrile illness in children younger than 36 months continues to be a concern with potentially serious consequences. Factors that suggest serious infection include age younger than one month, poor arousability, petechial rash, delayed capillary refill, increased respiratory effort, and overall physician assessment. Urinary tract infections are the most common serious bacterial infection in children younger than three years, so evaluation for such infections should be performed in those with unexplained fever. Abnormal white blood cell counts have poor sensitivity for invasive bacterial infections; procalcitonin and C-reactive protein levels, when available, are more informative. Chest radiography is rarely recommended for children older than 28 days in the absence of localizing signs. Lumbar puncture is not recommended for children older than three months without localizing signs; it may also be considered for those from one to three months of age with abnormal laboratory test results. Protocols such as Step-by-Step, Laboratory Score, or the Rochester algorithms may be helpful in identifying low-risk patients. Rapid influenza testing and tests for coronavirus disease 2019 (COVID-19) may be of value when those diseases are circulating. When empiric treatment is appropriate, suggested antibiotics include ceftriaxone or cefotaxime for infants one to three months of age and ampicillin with gentamicin or with cefotaxime for neonates. For children three months to three years of age, azithromycin or amoxicillin is recommended if pneumonia is suspected; for urinary infections, suggested antibiotics are cefixime, amoxicillin/clavulanate, or trimethoprim/sulfamethoxazole. Choice of antibiotics should reflect local patterns of microbial resistance.


title: [Application of noninvasive positive pressure ventilation for sleep disordered breathing in China].

text: After more than 30 years of development, noninvasive positive pressure ventilation (NPPV) has become one of the main treatments of sleep-disordered breathing (SDB) in the world. It is the wide application of this technology that makes breakthrough in SDB treatment, and has given rise to a new interdisciplinary area sleep medicine. In China, sleep medicine started in late of 1980's, in recent years, with the development of economy and the improvement of recognization, the application of NPPV in Chinese market has become one of the fastest growing in the world. NPPV technology also extends gradually to the treatments of patients with respiratory failure due to different causes, such as severe acute respiratory syndrome and COPD.


title: The role of viruses in the aetiology of community-acquired pneumonia in adults.

text: BACKGROUND The role of viruses in community-acquired pneumonia may have been previously underestimated. We aimed to study the incidence and clinical characteristics of community-acquired pneumonia (CAP) due to respiratory viruses in adults adding PCR to routine conventional laboratory tests. METHODS Consecutive adult patients diagnosed of CAP from January 2003 to March 2004 were included. Conventional tests including cultures of blood, sputum, urine antigen detection of Streptococcus pneumoniae and Legionella pneumophila, and paired serologies were routinely performed. Nasopharyngeal swabs were processed for study of respiratory viruses through antigen detection by indirect immunofluorescence assay, isolation of viruses in cell culture and detection of nucleic acids by two independent multiplex RT-PCR assays. According to the aetiology, patients were categorized in 4 groups: group 1, only virus detected; group 2, only bacteria detected; group 3, viral and bacterial; and group 4, unkown aetiology. RESULTS Of 340 patients diagnosed with CAP, 198 had nasopharyngeal swabs available and were included in this study. Aetiology was established in 112 (57%) patients: group 1, n=26 (13%); group 2, n=66 (33%); group 3, n=20 (10%). The most common aetiological agent was S. neumoniae (58 patients, 29%), followed by respiratory viruses (46 patients, 23%). Forty-eight respiratory viruses were identified: influenza virus A (n=16), respiratory syncytial virus A (n=5), adenovirus (n=8), parainfluenza viruses (n=5), enteroviruses (n=1), rhinoviruses (n=8) and coronavirus (n=5). There were two patients coinfected by two respiratory viruses. Serology detected 6 viruses, immunofluorescence 8, viral culture 12, and PCR 45. For the viruses that could be diagnosed with conventional methods, the sensitivity and specificity of RT-PCR was 85% and 92%, respectively. The only clinical characteristic that significantly distinguished viral from bacterial aetiology was a lower number of leukocytes (P=0.004). CONCLUSION PCR revealed that viruses represent a common aetiology of CAP. There is an urgent need to reconsider routine laboratory tests for an adequate diagnosis of respiratory viruses, as clinical characteristics are unable to reliably distinguish viral from bacterial aetiology.


title: N-terminal domain of the murine coronavirus receptor CEACAM1 is responsible for fusogenic activation and conformational changes of the spike protein.

text: The mouse hepatitis virus (MHV) receptor (MHVR), CEACAM1, has two different functions for MHV entry into cells: binding to MHV spike protein (S protein) and activation of the S protein to execute virus-cell membrane fusion, the latter of which is accompanied by conformational changes of the S protein. The MHVR comprising the N-terminal and fourth domains [R1(1,4)] displays these two activities, and the N domain is thought to be critical for binding to MHV. In this study, we have addressed whether or not the N domain alone is sufficient for these activities. We examined three types of soluble form MHVR (soMHVR), one consisting of the N domain alone [soR1(1)], one with the N and second domains [soR1(1,2)], and one [soR1(1,4)] expressed by recombinant baculoviruses. We assessed the abilities of these three types of soMHVR to bind to MHV, activate fusogenicity, and induce conformational changes of the S protein. All three types of soMHVR similarly bound to MHV, as examined by a solid-phase binding assay and neutralized MHV infectivity. They also activated S protein fusogenicity and induced its conformational changes with similar levels of efficiency. However, R1(1) expressed on the BHK cell surface failed to serve as a receptor in spite of a sufficient level of expression. The inability of expressed R1(1) to work as a receptor was due to the inaccessibility of virions to R1(1); however, these were accessible using the MHVR-specific monoclonal antibody CC1. These results collectively indicated that the N domain retains all biological activities necessary for receptor function.


title: Requirement of the 5'-end genomic sequence as an upstream cis-acting element for coronavirus subgenomic mRNA transcription.

text: We have developed a defective interfering (DI) RNA containing a chloramphenicol acetyltransferase reporter gene, placed behind an intergenic sequence, for studying subgenomic mRNA transcription of mouse hepatitis virus (MHV), a prototype coronavirus. Using this system, we have identified the sequence requirement for MHV subgenomic mRNA transcription. We show that this sequence requirement differs from that for RNA replication. In addition to the previously identified requirement for an intergenic (promoter) sequence, additional sequences from the 5' end of genomic RNA are required for subgenomic mRNA transcription. These upstream sequences include the leader RNA and a spacer sequence between the leader and intergenic sequence, which is derived from the 5' untranslated region and part of gene 1. The spacer sequence requirement is specific, since only the sequence derived from the 5' end of RNA genome, but not from other MHV genomic regions or heterologous sequences, could initiate subgenomic transcription from the intergenic sequence. These results strongly suggest that the wild-type viral subgenomic mRNAs (mRNA2 to mRNA7) and probably their counterpart subgenomic negative-sense RNAs cannot be utilized for mRNA amplification. Furthermore, we have demonstrated that a partial leader sequence present at the 5' end of genome, which lacks the leader-mRNA fusion sequence, could still support subgenomic mRNA transcription. In this case, the leader sequences of the subgenomic transcripts were derived exclusively from the wild-type helper virus, indicating that the MHV leader RNA initiates in trans subgenomic mRNA transcription. Thus, the leader sequence can enhance subgenomic transcription even when it cannot serve as a primer for mRNA synthesis. These results taken together suggest that the 5'-end leader sequence of MHV not only provides a trans-acting primer for mRNA initiation but also serves as a cis-acting element required for the transcription of subgenomic mRNAs. The identification of an upstream cis-acting element for MHV subgenomic mRNA synthesis defines a novel sequence requirement for regulating mRNA synthesis in RNA viruses.


Feline immunodeficiency virus pathogenesis and development of a dual-subtype feline-immunodeficiency-virus vaccine.


title: Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center.

text: BACKGROUND In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020. OBJECTIVES To present our findings and experiences as the first and largest center for COVID-19 patients in Israel. METHODS The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented. RESULTS Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1. CONCLUSIONS COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.


title: Making G8 leaders deliver: an analysis of compliance and health commitments, 1996-2006.

text: International health policy-makers now have a variety of institutional instruments with which to pursue their global and national health goals. These instruments range from the established formal multilateral organizations of the United Nations to the newer restricted-membership institutions of the Group of Eight (G8). To decide where best to deploy scarce resources, we must systematically examine the G8's contributions to global health governance. This assessment explores the contributions made by multilateral institutions such as the World Health Organization, and whether Member States comply with their commitments. We assessed whether G8 health governance assists its member governments in managing domestic politics and policy, in defining dominant normative directions, in developing and complying with collective commitments and in developing new G8-centred institutions. We found that the G8's performance improved substantially during the past decade. The G8 Member States function equally well, and each is able to combat diseases. Compliance varied among G8 Member States with respect to their health commitments, and there is scope for improvement. G8 leaders should better define their health commitments and set a one-year deadline for their delivery. In addition, Member States must seek WHO's support and set up an institution for G8 health ministers.


title: Global infectious disease surveillance and health intelligence.

text: Current concerns about the spread of infectious diseases, especially unexpected ("emerging") infections such as pandemic influenza or severe acute respiratory syndrome (SARS), have renewed focus on the critical importance of global early warning and rapid response. Although considerable progress has been made, many gaps remain. A number of the gaps can be addressed through increased political will, resources for reporting, improved coordination and sharing of information, raising clinicians' awareness, and additional research to develop more rigorous triggers for action. The increasing availability of communications and information technologies worldwide offers new opportunities for reporting even in low-capacity settings.


title: Is intralesional cidofovir worthwhile in juvenile recurrent respiratory papillomatosis?

text: OBJECTIVE To investigate the efficacy of intralesional cidofovir in the treatment of recurrent respiratory papillomatosis (RRP) in children. METHODS Prospective observational study of four consecutive children with RRP treated at an academic tertiary children's hospital. Laryngo-bronchoscopy was performed at three- to five-weekly intervals. Photodocumentation was obtained and disease severity assessed using an anatomical RRP severity score. Surgical debulking of large papillomas was then performed, and cidofovir (5 mg/ml) injected into any remaining papillomas as well as submucosally at the sites of resected papillomas. The efficacy of cidofovir was assessed by the change in papilloma severity score over the course of the treatment. RESULTS Complete disease remission was obtained in one patient, with a partial response seen in two others. One patient showed no significant response. The greatest beneficial effect was seen after the fourth cidofovir injection; however, two patients demonstrated a deterioration in severity scores after treatment was withheld at this point. Both responded well to further cidofovir injections. However, a clear plateau in the response to cidofovir was seen in all patients by the eighth injection. CONCLUSION Intralesional cidofovir may help control papilloma regrowth and reduce disease severity in many children with RRP. In most cases, cidofovir would appear to be less efficacious in causing disease eradication. There appears to be little evidence to support prolonged treatment regimes (i.e. more than eight treatments).


title: Chlorhexidine--pharmaco-biological activity and application.

text: OBJECTIVES Chlorhexidine (CHX) is one of the most widely used antiseptic, especially in dentistry. At low concentrations CHX is bacteriostatic and at high concentrations acts bactericidal causing cell death by cytolysis. In this study, we performed a systematic review of pharmaco-biological activity and application of CHX. MATERIALS AND METHODS Articles for inclusion in this review were retrieved from online databases PubMed/Medline. The selected papers were included in the present manuscript according to their relevance for the topic. RESULTS Totally 75 papers were enrolled in this research. CHX has strong biocidal activity against Gram-positive bacteria and weaker activity against Gram-negative bacteria. It is also active against yeasts, some dermatophytes and some lipophilic viruses. The most widely application CHX has found in dentistry and antisepsis. Numerous studies have confirmed the beneficial effects of CHX in reducing of plaque accumulation, in tooth caries, gingivitis, periodontitis and in alveolar osteitis. Unfortunately, CHX exhibits cytotoxic activity on human cells, can cause colorization of teeth and fillings, and its activity depends on the pH of the environment and the presence of organic substances. CONCLUSIONS CHX play a valuable role in the dentistry and antisepsis. However, it can also cause side effects, limiting its application time.


title: Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro.

text: We report here that glycyrrhizic acid (GL), a component of licorice root (Glycyrrhiza radix), is active against EBV replication in superinfected Raji cells in a dose-dependent fashion. The IC(50) values for viral inhibition and cell growth were 0.04 and 4.8mM, respectively. The selectivity index (ratio of IC(50) for cell growth to IC(50) for viral DNA synthesis) was 120. Time of addition experiments suggested that GL interferes with an early step of EBV replication cycle (possibly penetration). GL had no effect on viral adsorption, nor did it inactivate EBV particles. Thus, GL represents a new class of anti-EBV compounds with a mode of action different from that of the nucleoside analogs that inhibit viral DNA polymerase.


title: Detection and differentiation of porcine epidemic diarrhoea virus and transmissible gastroenteritis virus in clinical samples by multiplex RT-PCR.

text: A multiplex reverse-transcriptase-PCR (RT-PCR) procedure was developed for the simultaneous detection of porcine epidemic diarrhoea virus (PEDV) and transmissible gastroenteritis virus (TGEV) in preweaning pigs with diarrhoea. The membrane gene of PEDV and the nucleocapsid gene of TGEV were chosen as targets. The PCR products of PEDV and TGEV had molecular sizes of 412 and 612 base pairs, respectively. Primers from PEDV did not react with any TGEV tested and vice versa. In addition, the primers did not react with other pig viruses. The multiplex RT-PCR was able to detect 10 tissue culture-infective doses 50 per cent (TCID50)/ml of PEDV or TGEV with each of the primer sets for PEDV and TGEV, respectively. The RNAS of PEDV and TGEV were detected directly in intestinal and faecal samples from pigs infected experimentally with either virus. The results of the assay correlated well with the results of virus isolation. None of the five control specimens was positive. PEDV was detected in 10 intestinal and nine faecal samples, and among the nine positive faecal samples two were culture-negative. TGEV was also detected in 10 intestinal and nine faecal samples, and among the nine positive faecal samples, three were culture-negative.


title: Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice.

text: Following intranasal administration, the severe acute respiratory syndrome (SARS) coronavirus replicated to high titers in the respiratory tracts of BALB/c mice. Peak replication was seen in the absence of disease on day 1 or 2, depending on the dose administered, and the virus was cleared within a week. Viral antigen and nucleic acid were detected in bronchiolar epithelial cells during peak viral replication. Mice developed a neutralizing antibody response and were protected from reinfection 28 days following primary infection. Passive transfer of immune serum to naïve mice prevented virus replication in the lower respiratory tract following intranasal challenge. Thus, antibodies, acting alone, can prevent replication of the SARS coronavirus in the lung, a promising observation for the development of vaccines, immunotherapy, and immunoprophylaxis regimens.


title: Circulation of infectious bronchitis virus strains from Italy 02 and QX genotypes in Slovenia between 2007 and 2009.

text: Fourteen infectious bronchitis viruses (IBVs) detected in broiler, broiler breeder, and layer flocks in Slovenia between 2007 and 2009 were molecularly analyzed by reverse transcription-PCR and direct sequencing of the S1 gene. Phylogenetic analyses based on partial S1 gene sequences revealed that seven strains were classified as the Italy 02 genotype, a genetic group of IBV that has not previously been detected in Slovenia. Another seven strains were classified as the QX genotype. The results of phylogenetic analyses and epidemiologic investigations revealed that the genetic classification correlates with the geographic origins of the IBV strains. Greater genetic variability (maximum nucleotide and amino acid divergences were 4.8% and 9.9%, respectively) was observed within the Slovenian strains from the Italy 02 genotype detected between 2007 and 2009 than within strains from the QX genotype isolated in 2008 and 2009 (1.2% and 1.3%, respectively). The Slovenian strains classified as the Italy 02 genotype form a separate genetic cluster. These strains shared five specific amino acid substitutions that became fixed during the period of surveillance. Strains from the QX genotype that shared one specific amino acid substitution also form a separate genetic cluster.


title: [Early experience in laparoscopic radical prostatectomy using the laparoscopic device for umbilical access SILS Port].

text: Since 2007, various urological procedures have been performed with laparoendoscopic single-site surgery (LESS surgery), including nephrectomy, pyeloplasty, simple prostatectomy and, with the refinement of laparoscopic instrumentation, radical prostatectomy. This paper reports our initial experience in radical prostatectomy using the SILS Port from Covidiem and two lateral 5-mm trocars for triangulation. The SILS Port allows for accurate, simple insertion through a Hadson incision. The flexible port accommodates three 5-mm cannulas or two 5-mm cannulas and a 12-mm port for easier instrument exchange through a single incision. This approach decreases morbidity from bleeding, hernia and/or internal organ damage and improves cosmetic. One-port single-incision laparoscopy is part of the natural development of minimally invasive surgery. Future research is required to assess the intraoperative and postoperative benefits of LESS surgery as compared to standard laparoscopy.


docid: nqbfgocr

title: Prevalence of abnormal lipid levels among youths --- United States, 1999-2006.

text: Cardiovascular disease (CVD) is the leading cause of death among adults in the United States. CVD risk factors, including abnormal lipid levels and elevated body mass index (BMI), often emerge during childhood and adolescence. In 2008, the American Academy of Pediatrics (AAP) established recommendations for targeted screening of youths aged >or=2 years for abnormal blood lipid levels. To provide prevalence data on abnormal lipid levels among youths, eligibility for lipid screening based on BMI, and eligibility for therapeutic lifestyle counseling among overweight youths, CDC analyzed results from the National Health and Nutrition Examination Survey (NHANES) for 1999-2006. This report describes the results of that analysis, which found that the prevalence of abnormal lipid levels among youths aged 12-19 years was 20.3%. This prevalence varied by BMI; 14.2% of normal weight youths, 22.3% of overweight and 42.9% of obese had at least one abnormal lipid level. Among all youths, 32% had a high BMI and therefore would be candidates for lipid screening under AAP recommendations. Given the high prevalence of abnormal lipid levels among youths who are overweight and obese in this study, clinicians should be aware of lipid screening guidelines, especially recommendations for screening youths who are overweight or obese.


title: Differential susceptibility of cultured neural cells to the human coronavirus OC43.

text: By using cell-type-specific markers and neural cultures derived from various areas of the nervous system, it has been possible to identify various interactions between OC43 virus and mouse oligodendrocytes, neurons, astrocytes, and fibroblasts. Neurons derived from dorsal root ganglia produced viral antigen and infectious virus. Astrocytes and fibroblasts both produced viral antigen but not infectious virus. Oligodendrocytes produced neither infectious virus nor viral antigen. Human embryo brain cells, including astrocytes, were susceptible to OC43 infection but did not produce infectious virus.


Newly identified respiratory viruses.


title: Evaluation of neck masses in adults.

text: Neck masses are often seen in clinical practice, and the family physician should be able to determine the etiology of a mass using organized, efficient diagnostic methods. The first goal is to determine if the mass is malignant or benign; malignancies are more common in adult smokers older than 40 years. Etiologies can be grouped according to whether the onset/duration is acute (e.g., infectious), subacute (e.g., squamous cell carcinoma), or chronic (e.g., thyroid), and further narrowed by patient demographics. If the history and physical examination do not find an obvious cause, imaging and surgical tools are helpful. Contrast-enhanced computed tomography is the initial diagnostic test of choice in adults. Computed tomography angiography is recommended over magnetic resonance angiography for the evaluation of pulsatile neck masses. If imaging rules out involvement of underlying vital structures, a fine-needle aspiration biopsy can be performed, providing diagnostic information via cytology, Gram stain, and bacterial and acid-fast bacilli cultures. The sensitivity and specificity of fine-needle aspiration biopsy in detecting a malignancy range from 77% to 97% and 93% to 100%, respectively.


Implications of infectious agents on results of animal experiments. Report of the Working Group on Hygiene of the Gesellschaft für Versuchstierkunde--Society for Laboratory Animal Science (GV-SOLAS).


title: High level transient expression of the murine coronavirus haemagglutinin-esterase.

text: We have expressed the murine coronavirus haemagglutinin-esterase protein in a vaccinia virus/T7 RNA polymerase system. The levels of expression observed are significantly higher than those found in virus-infected cells. The expressed protein has both receptor-destroying (esterase) and receptor-binding (haemadsorption) activities. The use of this system will greatly facilitate analysis of the structure-function relationships of this protein.


docid: argqmtsa

title: Trends in collection, use and disclosure of personal information in contemporary health research: challenges for research governance.


title: Biologic, antigenic, and full-length genomic characterization of a bovine-like coronavirus isolated from a giraffe.

text: Coronaviruses (CoVs) possess large RNA genomes and exist as quasispecies, which increases the possibility of adaptive mutations and interspecies transmission. Recently, CoVs were recognized as important pathogens in captive wild ruminants. This is the first report of the isolation and detailed genetic, biologic, and antigenic characterization of a bovine-like CoV from a giraffe (Giraffa camelopardalis) in a wild-animal park in the United States. CoV particles were detected by immune electron microscopy in fecal samples from three giraffes with mild-to-severe diarrhea. From one of the three giraffe samples, a CoV (GiCoV-OH3) was isolated and successfully adapted to serial passage in human rectal tumor 18 cell cultures. Hemagglutination assays, receptor-destroying enzyme activity, hemagglutination inhibition, and fluorescence focus neutralization tests revealed close biological and antigenic relationships between the GiCoV-OH3 isolate and selected respiratory and enteric bovine CoV (BCoV) strains. When orally inoculated into a BCoV-seronegative gnotobiotic calf, GiCoV-OH3 caused severe diarrhea and virus shedding within 2 to 3 days. Sequence comparisons and phylogenetic analyses were performed to assess its genetic relatedness to other CoVs. Molecular characterization confirmed that the new isolate belongs to group 2a of the mammalian CoVs and revealed closer genetic relatedness between GiCoV-OH3 and the enteric BCoVs BCoV-ENT and BCoV-DB2, whereas BCoV-Mebus was more distantly related. Detailed sequence analysis of the GiCoV-OH3 spike gene demonstrated the presence of a deletion in the variable region of the S1 subunit (from amino acid 543 to amino acid 547), which is a region associated with pathogenicity and tissue tropism for other CoVs. The point mutations identified in the structural proteins (by comparing GiCoV-OH3, BCoV-ENT, BCoV-DB2, and BCoV-Mebus) were most conserved among GiCoV-OH3, BCoV-ENT, and BCoV-DB2, whereas most of the point mutations in the nonstructural proteins were unique to GiCoV-OH3. Our results confirm the existence of a bovine-like CoV transmissible to cattle from wild ruminants, namely, giraffes, but with certain genetic properties different from those of BCoVs.


Are community-based interventions effective in identifying and responding to emerging zoonotic infectious diseases?


title: Infection of HeLa cells by avian infectious bronchitis virus is dependent on cell status.

text: To investigate the adaptation of avian infectious bronchitis virus (IBV) in a human cell line may be beneficial to understanding the potential mechanisms of coronavirus interspecies infection. The current study addressed the poor replication of IBV in the HeLa human cell line demonstrated in previous reports. We showed that IBV strains M41, H52, H120 and Gray could be propagated in HeLa cells with distinct cytopathic effect. The virus titre in freshly dispersed HeLa cells was 1000-fold higher than in cell monolayers. Trypsin was not the determinant for the viral replication, suggesting that the restriction of IBV replication in HeLa cells is the result of intracellular events rather than the binding to or fusion with host cells. These IBV strains replicated to an average titre of 10(3.4+/-0.2)/0.1 ml median tissue culture infectious doses in freshly dispersed HeLa cells and maintained this titre for the first 12 passages. Then an approximately 10-fold increase (10(4.20+/-0.19)/0.1 ml) occurred in passage 13, which was maintained to passage 16, after which there was another, bigger rise to 10(6.6+/-0.3)/0.1 ml in passage 17. This titre was maintained until passage 24 when the experiment was terminated. The IBV M41 S1 gene was amplified and sequenced for passages 0, 5 and 21. There was only one amino acid replacement in the S1 protein, in passage 21. The presence of sialic acid on HeLa cells contributed to efficient virus replication, while human aminopeptidase N was not involved in the infection. Haemagglutinin activity gradually reduced with increased passages. These results indicated that the virus adaptation would probably be determined by host cell modification such as receptor glycosylation and different receptor utilization instead of viral gene mutation.


title: Concurrent experimentally induced infection with Eimeria bovis and coronavirus in unweaned dairy calves.

text: Over a period of 3 summers, 21 colostrum-fed Holstein bull calves, 1 to 3 days old, were assigned to 7 replicates, each consisting of 3 calves. Within each replicate of 3 calves, 2 were selected at random, to be given 100,000 to 146,000 sporulated coccidia oocysts (principally Eimeria bovis) orally 60 hours after arrival at the college research farm. On the thirteenth day after coccidia inoculation, 1 of the 2 calves that had been given coccidia and the third calf that had not been inoculated, were given coronavirus by intranasal and oral routes. Calves were observed daily, and consistency of feces was scored visually. Nasal swab specimens for indirect immunofluorescent antibody testing for coronavirus and fecal samples for oocyst determination were obtained approximately every third day. Of 7 calves that were given only coronavirus, 3 developed diarrhea of short duration. Of 7 calves that were given only coccidia oocysts, 6 developed diarrhea. All 7 calves inoculated initially with coccidia and subsequently with coronavirus developed diarrhea. For 5 of 7 replicates, calves that were given coccidia and coronavirus developed diarrhea first. When overall severity, measured by fecal score and by blood in the feces, was compared, calves inoculated with coccidia followed by coronavirus were more severely affected (P less than 0.05) than were calves that were given only coronavirus. Calves that were given only coccidia oocysts appeared more severely affected than calves that were given only coronavirus, but differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)


A Consequential Eight Years for Health Care and Public Health.


title: Intracellular location and translocation of silent and active poliovirus replication complexes.

text: Replication of poliovirus (PV) genomic RNA in HeLa cells has previously been found to start at distinct sites at the nuclear periphery. In the present study, the earliest steps in the virus replication cycle, i.e. the appearance and intracellular translocation of viral protein and negative-strand RNA prior to positive-strand RNA synthesis, were followed. During translation, positive-strand RNA and newly synthesized viral protein presented as a dispersed endoplasmic reticulum (ER)-like pattern. Concomitant with translation, individual PV vesicle clusters emerged at the ER and formed nascent replication complexes, which contained newly synthesized negative-strand RNA. The complexes rapidly moved centripetally, in a microtubule-dependent way, to the perinuclear area to engage in positive-strand viral RNA synthesis. Replication complexes made transcriptionally silent with guanidine/HCl followed the anterograde membrane pathway to the Golgi complex within the microtubule-organizing centre (MTOC), whereas replication complexes active in positive-strand RNA synthesis were retained at the nuclear periphery. If the silent replication complexes that had accumulated at the MTOC were released from the guanidine block, transcription was not readily resumed. Rather, positive-strand RNA was redistributed back to the ER to start, after a lag phase, translation, followed by negative- and positive-strand RNA synthesis in replication complexes migrating to the nuclear periphery. As some of the findings appear to be in contrast to events reported in cell-free guanidine-synchronized translation/transcription systems, implications for the comparison of in vitro systems with the living cell are discussed.


title: [First detection of human metapneumovirus in a child with respiratory syndrome in Hungary].

text: INTRODUCTION Human metapneumovirus was identified in 2001 as a respiratory-tract pathogen that has been classified as a new genera in family Paramyxoviridae. AIMS Molecular detection of human metapneumovirus in Hungary. MATERIALS AND METHODS Human metapneumovirus was identified in nasopharyngeal aspirate amplification of the viral fusion and nucleocapsid genes by reverse transcription-polymerase chain reaction followed by sequencing and phylogenetic analysis. RESULTS A 4 years-old girl with chronic respiratory syndrome chronically treated with anti-asthma drugs was admitted to hospital in November 2005 with acute respiratory syndrome and atelectasis. Nasopharyngeal aspirate was negative for common bacteria by culture and for influenza and coronavirus by reverse transcription-polymerase chain reaction. By contrast, specimen was positive by reverse transcription-polymerase chain reaction and was confirmed by sequencing both genes (nucleocapsid and fusion) of human metapneumovirus. Human metapneumovirus (HUN 05-L20) clustered into the subgroup B1 has the closest nucleotide similarity (98%) to JPS03-194 (AY530094) detected in Japan. CONCLUSIONS Human metapneumovirus contributes as an etiological agent of acute lower and upper respiratory tract infection especially in winter season in children with bronchiolitis, pneumonia or episodes of asthma exacerbation in Hungary, too.


Non-pharmaceutical interventions.


title: Rotavirus and coronavirus outbreak: etiology of annual diarrhea in Costa Rican children.

text: In Costa Rica, an annual outbreak of infant diarrheal disease (December and January) was reported since 1976, and rotavirus was incriminated later as the main etiological agent (1976-1981). Apparently the disease has not been systematically studied in Costa Rica after 1981. For that reason the occurrence of the outbreak was retrospectively documented for 1993-1995 and etiology was studied in 48 children treated for diarrhea at the Nacional Children Hospital (capital city of San Jose) during December, 1994 and January, 1995. Rotavirus (33%) and coronavirus (27%) were the main agents. To our knowledge, this is the first time that these viruses are incriminated in an outbreak of diarrhea.


NICE recommends photodynamic therapy for certain patients with macular degeneration.


title: Summary of Notifiable Diseases - United States, 2011.

text: The Summary of Notifiable Diseases - United States, 2011 contains the official statistics, in tabular and graphic form, for the reported occurrence of nationally notifiable infectious diseases in the United States for 2011. Unless otherwise noted, the data are final totals for 2011 reported as of June 30, 2012. These statistics are collected and compiled from reports sent by state health departments and territories to the National Notifiable Diseases Surveillance System (NNDSS), which is operated by CDC in collaboration with the Council of State and Territorial Epidemiologists (CSTE).


title: Immunofluorescence assay for detection of the nucleocapsid antigen of the severe acute respiratory syndrome (SARS)-associated coronavirus in cells derived from throat wash samples of patients with SARS.

text: An antigen detection assay for severe acute respiratory syndrome (SARS) coronavirus was established in this study by an indirect immunofluorescence test, which utilized cells derived from throat wash samples of patients with SARS and a rabbit serum that recognized the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) but not that of other human coronavirus tested. It detected SARS-CoV in 11 of 17 (65%) samples from SARS patients as early as day 2 of illness but in none of the 10 samples from healthy controls. Compared with other diagnostic modalities for detecting SARS-CoV, this assay is simpler, more convenient, and economical. It could be an alternative for early and rapid diagnosis, should SARS return in the future.


title: Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants.

text: In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.