title: Development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (HVAC) filters.

text: The aim of the work presented here is to study the effectiveness of building air handling units (AHUs) in serving as high volume sampling devices for airborne bacteria and viruses. An HVAC test facility constructed according to ASHRAE Standard 52.2-1999 was used for the controlled loading of HVAC filter media with aerosolized bacteria and virus. Nonpathogenic Bacillus subtilis var. niger was chosen as a surrogate for Bacillus anthracis. Three animal viruses; transmissible gastroenteritis virus (TGEV), avian pneumovirus (APV), and fowlpox virus were chosen as surrogates for three human viruses; SARS coronavirus, respiratory syncytial virus, and smallpox virus; respectively. These bacteria and viruses were nebulized in separate tests and injected into the test duct of the test facility upstream of a MERV 14 filter. SKC Biosamplers upstream and downstream of the test filter served as reference samplers. The collection efficiency of the filter media was calculated to be 96.5 +/- 1.5% for B. subtilis, however no collection efficiency was measured for the viruses as no live virus was ever recovered from the downstream samplers. Filter samples were cut from the test filter and eluted by hand-shaking. An extraction efficiency of 105 +/- 19% was calculated for B. subtilis. The viruses were extracted at much lower efficiencies (0.7-20%). Our results indicate that the airborne concentration of spore-forming bacteria in building AHUs may be determined by analyzing the material collected on HVAC filter media, however culture-based analytical techniques are impractical for virus recovery. Molecular-based identification techniques such as PCR could be used.


title: Don't be scared, be angry: the politics and ethics of Ebola.

text: The current outbreak of Ebola virus disease in West Africa is the worst so far. The unprecedented extent of mortality and morbidity in this outbreak has followed more from imposition of neoliberal economic policies on the countries affected than from the biological virulence of Ebola virus. The lack of vaccines and medications for Ebola virus disease is evidence that markets cannot reliably supply treatments for epidemic diseases. We attribute the current difficulties in containment chiefly to the erosion or non-development of the health and medical infrastructure needed to respond effectively, as a direct result of market-privileging policies imposed in the interests of wealthy nations. These events and responses hold lessons for public health priorities in Australia.


title: Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate.

text: Fusion proteins of enveloped viruses categorized as class I are typified by two distinct heptad repeat domains within the transmembrane subunit. These repeats are important structural elements that assemble into the six-helix bundles characteristic of the fusion-activated envelope trimer. Peptides derived from these domains can be potent and specific inhibitors of membrane fusion and virus infection. To facilitate our understanding of retroviral entry, peptides corresponding to the two heptad repeat domains of the avian sarcoma and leukosis virus subgroup A (ASLV-A) TM subunit of the envelope protein were characterized. Two peptides corresponding to the C-terminal heptad repeat (HR2), offset from one another by three residues, were effective inhibitors of infection, while two overlapping peptides derived from the N-terminal heptad repeat (HR1) were not. Analysis of envelope mutants containing substitutions within the HR1 domain revealed that a single amino acid change, L62A, significantly reduced sensitivity to peptide inhibition. Virus bound to cells at 4 degrees C became sensitive to peptide within the first 5 min of elevating the temperature to 37 degrees C and lost sensitivity to peptide after 15 to 30 min, consistent with a transient intermediate in which the peptide binding site is exposed. In cell-cell fusion experiments, peptide inhibitor sensitivity occurred prior to a fusion-enhancing low-pH pulse. Soluble receptor for ASLV-A induces a lipophilic character in the envelope which can be measured by stable liposome binding, and this activation was found to be unaffected by inhibitory HR2 peptide. Finally, receptor-triggered conformational changes in the TM subunit were also found to be unaffected by inhibitory peptide. These changes are marked by a dramatic shift in mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, from a subunit of 37 kDa to a complex of about 80 kDa. Biotinylated HR2 peptide bound specifically to the 80-kDa complex, demonstrating a surprisingly stable envelope conformation in which the HR2 binding site is exposed. These experiments support a model in which receptor interaction promotes formation of an envelope conformation in which the TM subunit is stably associated with its target membrane and is able to bind a C-terminal peptide.


title: Impact of enforcing the Labour Ordinance, with 1-in-7-day off for hospital doctors, on weekend hospital discharge rate.

text: BACKGROUND After enforcing the Labour Ordinance, hospital doctors must have 1 day off-work every week. In this study, we aimed to evaluate its impact on the discharge pattern from an acute medical hospital. METHODS We undertook a hospital-based ecologic study with before-after design using the clinical management database of patient discharge records of all acute medical wards in a hospital from January to March 2002 (1 year before new system) and from January to March 2004 (1 year after restricted weekend service). The main outcome measures were the daily discharge rates for the two periods. The odds of being discharged on a Saturday were estimated by multivariate analyses. RESULTS The number of patient discharge on a Saturday was substantially lower in 2004 as compared to 2002 (47.5 +/- 8.5 per Saturday versus 70.5 +/- 11.1 per Saturday, respectively, p < 0.001). A statistically significant decreased trend was noted in the weekend discharge rate in 2002 and 2004 (Poisson p-value for change in discharge rate, p < 0.001). On the other hand, the number of patient discharges on weekdays did not differ between the two periods. Consistently fewer patients were being discharged on Sundays and Mondays as compared to the rest of the week days in both periods. Compared with study period 2002, patients hospitalized in 2004 (with limited weekend service) had significantly lower multivariate-adjusted odds of being discharged on a Saturday (odds ratio of 0.70; 95 percent confidence interval 0.72-0.89, p < 0.0001). CONCLUSIONS Length of hospital stay is influenced by the health care system delivery apart from clinical factors. Restricted weekend services in an acute medical hospital setting substantially lengthen the hospital stay, and might therefore entail a major financial burden.


title: Effect of regular exercise on health and disease.

text: It is known for a long time that exercise increases physical adequacy, has beneficial effects on the general health condition as well as a playing preventing role against various disease states. To decrease the risk of disease and maintain good health, the natural defense system of the organism needs to be strengthened. It is thought that in addition to increasing the body's resistance to disease through the strengthening of the immune system, decreases the convalescence time, increases work efficiency and improves the sportive performance of the individual all which would contribute positively to the national economy. The positive effects of regular exercising of aerobic nature such as strengthening of the immune system, protection against diseases as well as its positive effects on quality of life will help to emphasize the importance of physical exercise and improve the general view of sports by society.


title: Viral aetiology of enzootic pneumonia in Danish dairy herds: diagnostic tools and epidemiology.

text: Ten outbreaks of calf respiratory disease in Danish dairy herds were investigated by lung lavage, and in eight of the herds paired blood samples were tested serologically. In six of the 10 herds bovine respiratory syncytial virus (BRSV) antigen was detected in the lung lavage fluids. In only one calf was coronavirus and BRSV detected simultaneously. The paired blood samples confirmed that four of the herds were BRSV-infected, and in one herd the BRSV infection was diagnosed by the paired blood samples alone. Significant increases in antibody titres against coronavirus were observed in two herds, both in combination with other virological agents. No adenovirus antigen was detected in any of the lavage samples, but in two herds a significant increase in antibody titres against adenovirus was observed. Parainfluenza-3 (PI-3) virus was not detected in the lung lavage fluids, and in four of the herds, no antibodies to PI-3 were detected. In three herds no viral involvement could be found. The findings suggest that BRSV may be an important causative agent in calf respiratory disease in Denmark, even in very young calves.


title: Von Willebrand gene tracking by single-tube automated fluorescent analysis of four short tandem repeat polymorphisms.

text: Molecular diagnosis of von Willebrand disease (VWD) has been hampered by the large size and complex genomic characteristics of the gene involved. For this reason, indirect methods using intragenic polymorphic markers described along the von Willebrand factor (VWF) gene are valuable tools for gene monitoring and linkage analysis. Several studies have demonstrated the four commonly utilized short tandem repeats (STRs), three located in intron 40 and one in the promoter region of the VWF gene, to be highly informative for this task. Our objective was t o develop a rapid, automated method to simultaneously analyze these four STRs for VWF gene tracking. Amplification of the four loci is achieved in a single multiplex fluorescent PCR which is then analyzed in the same run by capillary electrophoresis. Data processing with GeneScan and Genotyper software has simplified management and tabulation of the resulting haplotypes. Analysis of the VWF gene in DNA from 102 individuals (204 chromosomes) revealed that the three STRs within intron 40 showed significant linkage disequilibrium against each other but not against the VWP locus. Moreover, the combination of the four markers offers a high heterozygosity rate (>99%) that improves tracing VWF gene inheritance. In conclusion, the automated fluorescent capillary electrophoresis method presented here is an extremely rapid, simple and highly informative technique for association studies between VWD and the VWF gene in addition to genetic counseling and prenatal diagnosis by precise linkage analysis in VWD-affected families.


title: Beyond the physician charter: reflections on medical professionalism.

text: The numerous challenges now facing the profession of medicine have led to an intense focus on professionalism by individual physicians and by their professional and academic organizations. In 2002, a distinguished group of leaders in internal medicine created the Physician Charter, which calls on physicians to reaffirm medical professionalism through commitment to three principles and 10 responsibilities. The Charter reflects a duty-based ethic that is chiefly concerned with physician competence. This article offers a critical analysis of the Physician Charter from the perspective of the traditional values of medicine as articulated in medical oaths and championed by leaders of past generations, exemplified by William Osler. The authors argue that medical professionalism should reflect the values of a virtue-based ethic that stresses compassion and beneficence, rather than the values of a duty-based ethic. The challenges that now confront the practice of medicine can be addressed successfully only to the extent that physicians promote virtue-ethics, act collectively in the public interest, and render service that clearly transcends their own self-interests.


title: Disseminated histoplasmosis in a Bengal tiger (Panthera tigris).

text: Disseminated infection with Histoplasma capsulatum was diagnosed in a 7-yr-old female Bengal tiger (Panthera tigris). Clinical signs were nonspecific with the exception of brief periods of tachypnea for 5 days prior to death. H. capsulatum organisms were found in the lungs, tracheobronchial lymph nodes, and liver. Diagnosis was confirmed by tracheal wash, urine H. capsulatum enzyme immunoassay, and necropsy results. This report represents the first published account of disseminated histoplasmosis in a tiger.


title: Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.


title: Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata.

text: SARS-coronavirus (SARS-CoV) encodes a main protease, 3CLpro, which plays an essential role in the viral life cycle and is currently the prime target for discovering new anti-coronavirus agents. In this article, we report our success in developing a novel red-shifted (RS) fluorescence-based assay for 3CLpro and its application for identifying small-molecule anti-SARS agents from marine organisms. We have synthesised and characterised the first generation of a red-shifted internally quenched fluorogenic substrate (RS-IQFS) for 3CLpro based on resonance energy transfer between the donor and acceptor pair CAL Fluor Red 610 and Black Hole Quencher-1 (Km and kcat values of 14 microM and 0.65 min-1). The RS-IQFS primary sequence was selected based on the results of our screening analysis of 3CLpro performed using a series of blue-shifted (BS)-IQFSs corresponding to the 3CLpro-mediated cleavage junctions of the SARS-CoV polyproteins. In contrast to BS-IQFSs, the RS-IQFS was not susceptible to fluorescence interference from coloured samples and allowed for successful screening of marine natural products and identification of a coumarin derivative, esculetin-4-carboxylic acid ethyl ester, a novel 3CLpro inhibitor (IC50=46 microM) and anti-SARS agent (EC50=112 microM; median toxic concentration>800 microM) from the tropical marine sponge Axinella corrugata.


title: The proportion of specific viral subpopulations in attenuated Arkansas Delmarva poultry industry infectious bronchitis vaccines influences vaccination outcome.

text: We investigated the significance of differing proportions of specific subpopulations among commercial Arkansas (Ark) Delmarva poultry industry (DPI) vaccines with regard to vaccination outcome. Two ArkDPI-derived vaccines that contain a higher proportion of viruses with S1 genes that become selected during replication in chickens exhibited more rapid establishment of those selected subpopulations in chickens, produced significantly higher viral loads in tears, and induced higher antibody responses compared with two other ArkDPI vaccines with lower proportions of viruses that become selected in chickens. The presence of higher proportions of selected subpopulations was also associated with a significantly higher incidence of respiratory signs early after vaccination and in some cases more severe tracheal lesions. However, one of the ArkDPI-derived vaccines with a lower proportion of selected subpopulations, despite producing a lower viral load in tears, also induced a higher incidence of respiratory signs later after vaccination and more severe tracheal lesions. Furthermore, one of the ArkDPI-derived vaccines with a higher proportion of selected subpopulations, despite producing a higher viral loads in tears, resulted in less severe tracheal damage. These discrepancies suggest that infectious bronchitis virus (IBV) load in tears may not always predict degree of tracheal damage and that phenotypic characteristics other than S1 may also be involved in severity of vaccine reactions following ArkDPI vaccine administration. We observed lower antibody responses to the vaccines that produced lower viral loads, which might contribute to the persistence of Ark serotype IBV vaccines observed in commercial flocks.


title: [Clinical Characteristics of Coronavirus Disease 2019 in the Netherlands].

text: Since February, 27 2019, when the first patient with coronavirus disease 2019 (Covid-19) was identified in the Netherlands it has rapidly spread throughout the country. Exactly one month later 8603 people had been tested positive for SARS-CoV-2, 2500 patients were or had been admitted to the hospital and 456 patients died. Here the clinical data are summarized of the first 236 patients that have been admitted to hospitals in Uden, Breda and Tilburg which were all at the centre of the initial outbreak in the Netherlands. This commentary focusses on the clinical characteristics of the patients that are currently being treated on the Dutch clinical corona units, their medical management and the first clinical outcomes. Data is compared to current cohort studies from China, Italy and the United States.


Health assembly rebuffs Taiwan's bid for 'observer' status.


The molecular biology of arteriviruses.


title: Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies.

text: Hendra virus (HeV) and Nipah virus (NiV) are closely related emerging viruses comprising the Henipavirus genus of the Paramyxovirinae. Each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. These viruses infect cells by a pH-independent membrane fusion event mediated by their attachment (G) and fusion (F) envelope glycoproteins (Envs). Seven Fabs, m101 to -7, were selected for their significant binding to a soluble form of Hendra G (sG) which was used as the antigen for panning of a large naïve human antibody library. The selected Fabs inhibited, to various degrees, cell fusion mediated by the HeV or NiV Envs and virus infection. The conversion of the most potent neutralizer of infectious HeV, Fab m101, to immunoglobulin G1 (IgG1) significantly increased its cell fusion inhibitory activity: the 50% inhibitory concentration was decreased more than 10-fold to approximately 1 microg/ml. The IgG1 m101 was also exceptionally potent in neutralizing infectious HeV; complete (100%) neutralization was achieved with 12.5 microg/ml, and 98% neutralization required only 1.6 microg/ml. The inhibition of fusion and infection correlated with binding of the Fabs to full-length G as measured by immunoprecipitation and less with binding to sG as measured by enzyme-linked immunosorbent assay and Biacore. m101 and m102 competed with the ephrin-B2, which we recently identified as a functional receptor for both HeV and NiV, indicating a possible mechanism of neutralization by these antibodies. The m101, m102, and m103 antibodies competed with each other, suggesting that they bind to overlapping epitopes which are distinct from the epitopes of m106 and m107. In an initial attempt to localize the epitopes of m101 and m102, we measured their binding to a panel of 11 G alanine-scanning mutants and identified two mutants, P185A and Q191 K192A, which significantly decreased binding to m101 and one, G183, which decreased binding of m102 to G. These results suggest that m101 to -7 are specific for HeV or NiV or both and exhibit various neutralizing activities; they are the first human monoclonal antibodies identified against these viruses and could be used for treatment, prophylaxis, and diagnosis and as research reagents and could aid in the development of vaccines.


title: Using the hierarchy of control technologies to improve healthcare facility infection control: lessons from severe acute respiratory syndrome.

text: Health care facilities need to review their infection control plans to prepare for the possible resurgence of severe acute respiratory syndrome, other emerging pathogens, familiar infectious agents such as tuberculosis and influenza, and bioterrorist threats. This article describes the classic "hierarchy of control technologies" that was successfully used by occupational and environmental medicine professionals to protect workers from illness and death during the resurgence of tuberculosis in the 1990s. Also discussed are related guidelines from building and equipment professional organizations and novel infection control techniques used successfully by various hospitals in Asia, Canada, and the United States during the 2003 severe acute respiratory syndrome epidemic. Taken together, they suggest a framework upon which a comprehensive infection control plan can be crafted to prevent the spread of deadly infectious agents to health care workers (clinicians and paraprofessionals), uninfected patients and visitors.


title: Phase Detection of the Two-port FPW Sensor for Biosensing.

text: In this study, we provided a comprehensive methodology for designing and integrating miniature system in the biosensor application. In general, the network analyzer is commonly used for acoustic wave sensor measurement. However, it is remarkably inconvenient for portable use. Therefore, we presented a readout concept, which was focused on the miniaturization of the flexural plate wave (FPW) sensor system by integrating phase detection circuit. The miniature system includes a Wien-Bridge oscillator, a voltage following, a FPW device, a phase-locked loop, a phase detector, a MCU, and a LCM display. This work succeeded in integrating all the subsystems. And the core technology of the system is the phase detection function. The results showed the phase shift resolution is 10 mV/1°.


title: Experiences and implications of social workers practicing in a pediatric hospital environment affected by SARS.

text: This phenomenological study's purpose was threefold: to detail the experiences of social workers practicing in a hospital environment affected by severe acute respiratory syndrome (SARS), to describe essential themes and structures of social work practices within this crisis environment, and to explore recommendations for better preparedness to meet similar crises in the future. The sudden onset of SARS in hospital settings created an immediate necessity to study this phenomenon as hospitals and health care professionals struggle to adapt to this new epidemic environment. This study is the first using qualitative research to investigate the unique perspective of social workers in an epidemic environment. The results reflect the social workers' subjective experience of their interventions with patients and families and indicate that a number of professional tenets, such as advocacy, family-centered approach, knowledge of systems, open communication, and ethics effectively supported social work practice in a crisis environment.


title: Network analysis in public health: history, methods, and applications.

text: Network analysis is an approach to research that is uniquely suited to describing, exploring, and understanding structural and relational aspects of health. It is both a methodological tool and a theoretical paradigm that allows us to pose and answer important ecological questions in public health. In this review we trace the history of network analysis, provide a methodological overview of network techniques, and discuss where and how network analysis has been used in public health. We show how network analysis has its roots in mathematics, statistics, sociology, anthropology, psychology, biology, physics, and computer science. In public health, network analysis has been used to study primarily disease transmission, especially for HIV/AIDS and other sexually transmitted diseases; information transmission, particularly for diffusion of innovations; the role of social support and social capital; the influence of personal and social networks on health behavior; and the interorganizational structure of health systems. We conclude with future directions for network analysis in public health.


title: The anti-inflammatory and anti-nociceptive activities of Patrinia villosa and its mechanism on the proinflammatory cytokines of rats with pelvic inflammation.

text: This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX group), and model-control group (CON group) to perform an ear edema test, a carrageenin-induced paw edema test, a cotton pellet-induced granuloma formation test, and an acetic acid-induced writhing test. The model rats with pelvic inflammation were established, and the serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in each group was detected with the Enzyme-Linked ImmunoSorbent Assay (ELISA). The results of the ear edema test, carrageenin-induced paw edema test, cotton pellet-induced granuloma formation test, and acetic acid-induced writhing test all showed that Patrinia villosa had strong anti-inflammatory and anti-nociceptive effects. In the experiment using model rats with pelvic inflammation, we found that the serum levels of IL-6, IL-8 and TNF-α in PV and DEX group were all significantly lower than those of the CON group, and the serum levels of IL-6 and IL-8 in PV group were significantly lower than those of the DEX group. Patrinia villosa, with its strong anti-inflammatory and anti-nociceptive activities, can be used to treat pelvic inflammation and to relieve the associated pain.


title: Amino acid residues in the cytoplasmic domain of the Mason-Pfizer monkey virus glycoprotein critical for its incorporation into virions.

text: Assembly of an infectious retrovirus requires the incorporation of the envelope glycoprotein complex during the process of particle budding. We have recently demonstrated that amino acid substitutions of a tyrosine residue in the cytoplasmic domain block glycoprotein incorporation into budding Mason-Pfizer monkey virus (M-PMV) particles and abrogate infectivity (C. Song, S. R. Dubay, and E. Hunter, J. Virol. 77:5192-5200, 2003). To investigate the contribution of other amino acids in the cytoplasmic domain to the process of glycoprotein incorporation, we introduced alanine-scanning mutations into this region of the transmembrane protein. The effects of the mutations on glycoprotein biosynthesis and function, as well as on virus infectivity, have been examined. Mutation of two cytoplasmic residues, valine 20 and histidine 21, inhibits viral protease-mediated cleavage of the cytoplasmic domain that is observed during virion maturation, but the mutant virions show only moderately reduced infectivity. We also demonstrate that the cytoplasmic domain of the M-PMV contains three amino acid residues that are absolutely essential for incorporation of glycoprotein into virions. In addition to the previously identified tyrosine at residue 22, an isoleucine at position 18 and a leucine at position 25 each mediate the process of incorporation and efficient release of virions. While isoleucine 18 may be involved in direct interactions with immature capsids, antibody uptake studies showed that leucine 25 and tyrosine 22 are part of an efficient internalization signal in the cytoplasmic domain of the M-PMV glycoprotein. These results demonstrate that the cytoplasmic domain of M-PMV Env, in part through its YXXL-mediated endocytosis and intracellular trafficking signals, plays a critical role in the incorporation of glycoprotein into virions.


title: Successful endovascular extraction of newer generation Angio-Seal collagen plug and anchor after acute embolization.

text: A 75-year-old woman with past medical history of coronary bypass, atrial fibrillation, mitral valve repair undergoes percutaneous coronary intervention of left circumflex artery with a drug eluting stent. An Anglo-Seal vascular closure device was used post procedure to obtain hemostasis. Shortly after deployment, frank bleeding was observed necessitating manual compression at the arteriotomy site. After hemostasis was achieved, the right lower extremity was found to be pale, bluish with feeble pulses. Doppler ultrasound was emergently performed revealing decreased blood flow after mid superficial femoral artery (SFA) and an echo lucent object lodged luminally in the SFA. Patient was urgently taken to the vascular laboratory where an Angio-Seal device, including the collagen plug and anchor, was successfully removed endovascularly patient made full recovery and was discharged home the following day.


title: Viral Pneumonias in Forensic Autopsies: Evaluation and Classification of Histopathologic Changes With Microbiologic Correlation.

text: Lower respiratory infections are commonly due to viruses and are the third largest cause of death. Respiratory tract viruses have a tendency to target the specific regions in the lung and can harm the host via direct effect of the virus and the host's inflammatory response. In this study, relationships between morphologic changes in the lung and the viral agent type isolated in the lung by the polymerase chain reaction technique were investigated. This study was performed retrospectively at 113 autopsy cases in the Council of Forensic Medicine in Istanbul. Slides from the lung tissues diagnosed as interstitial pneumonia and detected viral agent in polymerase chain reaction were evaluated and reviewed under light microscope by 2 pathologists simultaneously according to predetermined bronchiolar, alveolar, and interstitial findings. Alveolar findings were detected in 108 cases (95.6%), whereas interstitial and bronchiolar findings were detected in 91 (80.5%) and 38 (33.6%) cases, respectively. Intra-alveolar edema was the most common alveolar finding. Some findings such as multinucleated syncytial cells and smudge cells can aid the search for etiologic agent. Interstitial inflammation was the most common histopathologic finding in the lung in viral infections and the most prominent clue to viral infections in the lung histopathologically without discrimination of viral agent type.


title: Antibody responses of cattle with respiratory coronavirus infections during pathogenesis of shipping fever pneumonia are lower with antigens of enteric strains than with those of a respiratory strain.

text: The serum antibody responses of cattle with respiratory coronavirus infections during the pathogenesis of shipping fever pneumonia were analyzed with different bovine coronavirus antigens, including those from a wild-type respiratory bovine coronavirus (RBCV) strain (97TXSF-Lu 15-2) directly isolated from lung tissue from a fatally infected bovine, a wild-type enteropathogenic bovine coronavirus (EBCV) strain (Ly 138-3), and the highly cell culture-adapted, enteric prototype strain (EBCV L9-81). Infectivity-neutralizing (IN) and hemagglutinin-inhibiting (HAI) activities were tested. Sequential serum samples, collected during the onset of the respiratory coronavirus infection and at weekly intervals for 5 weeks thereafter, had significantly higher IN and HAI titers for antigens of RBCV strain 97TXSF-Lu15-2 than for the wild-type and the highly cell culture-adapted EBCV strains, with P values ranging from <0.0001 to 0.0483. The IN and HAI antibody responses against the two EBCV strains did not differ significantly, but the lowest titers were detected with EBCV strain L9-81.


title: Equine infectious anemia virus entry occurs through clathrin-mediated endocytosis.

text: Entry of wild-type lentivirus equine infectious anemia virus (EIAV) into cells requires a low-pH step. This low-pH constraint implicates endocytosis in EIAV entry. To identify the endocytic pathway involved in EIAV entry, we examined the entry requirements for EIAV into two different cells: equine dermal (ED) cells and primary equine endothelial cells. We investigated the entry mechanism of several strains of EIAV and found that both macrophage-tropic and tissue culture-adapted strains utilize clathrin-coated pits for entry. In contrast, a superinfecting strain of EIAV, EIAV(vMA-1c), utilizes two mechanisms of entry. In cells such as ED cells that EIAV(vMA-1c) is able to superinfect, viral entry is pH independent and appears to be mediated by plasma membrane fusion, whereas in cells where no detectable superinfection occurs, EIAV(vMA-1c) entry that is low-pH dependent occurs through clathrin-coated pits in a manner similar to wild-type virus. Regardless of the mechanism of entry being utilized, the internalization kinetics of EIAV is rapid with 50% of cell-associated virions internalizing within 60 to 90 min. Cathepsin inhibitors did not prevent EIAV entry, suggesting that the low-pH step required by wild-type EIAV is not required to activate cellular cathepsins.


title: A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

text: During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, daily reporting mechanism in the RDMS was established during the London 2012 Olympic and Paralympic Games. Furthermore, this system can be quickly adapted and used to monitor future influenza pandemics and other major outbreaks of respiratory infectious disease, including novel pathogens.


Characterization of nucleocapsid-M protein interaction in murine coronavirus.


title: Structural protein requirements in equine arteritis virus assembly.

text: Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. EAV particles contain seven structural proteins: the nucleocapsid protein N, the unglycosylated envelope proteins M and E, and the N-glycosylated membrane proteins GP(2b) (previously named G(S)), GP(3), GP(4), and GP(5) (previously named G(L)). Proteins N, M, and GP(5) are major virion components, E occurs in virus particles in intermediate amounts, and GP(4), GP(3), and GP(2b) are minor structural proteins. The M and GP(5) proteins occur in virus particles as disulfide-linked heterodimers while the GP(4), GP(3), and GP(2b) proteins are incorporated into virions as a heterotrimeric complex. Here, we studied the effect on virus assembly of inactivating the structural protein genes one by one in the context of a (full-length) EAV cDNA clone. It appeared that the three major structural proteins are essential for particle formation, while the other four virion proteins are dispensable. When one of the GP(2b), GP(3), or GP(4) proteins was missing, the incorporation of the remaining two minor envelope glycoproteins was completely blocked while that of the E protein was greatly reduced. The absence of E entirely prevented the incorporation of the GP(2b), GP(3), and GP(4) proteins into viral particles. EAV particles lacking GP(2b), GP(3), GP(4), and E did not markedly differ from wild-type virions in buoyant density, major structural protein composition, electron microscopic appearance, and genomic RNA content. On the basis of these results, we propose a model for the EAV particle in which the GP(2b)/GP(3)/GP(4) heterotrimers are positioned, in association with a defined number of E molecules, above the vertices of the putatively icosahedral nucleocapsid.


title: Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections.

text: Persistent viral infections causing serious diseases derive, primarily, from altered function of the immune system. Knowledge of the very complex composition and function of the innate and adaptive branches of the immune system is essential to understanding persistent infection. The best solution to the problem of persistent infection is by prevention using prophylactic vaccines. Hit and run viruses evade immune destruction by infecting new hosts and rarely persist. Hit and stay viruses evade immune control by sequestration, blockade of antigen presentation, cytokine escape, evasion of natural killer cell activities, escape from apoptosis, and antigenic change. Twelve prophylactic vaccines against hit and run agents exist, and there are only three vaccines against hit and stay viruses, all of which are of DNA composition. Several new vaccines against hit and stay viruses are feasible, but protective vaccines against RNA HIV and hepatitis C agents are highly unlikely, short of a major breakthrough. Therapeutic vaccines are very improbable without a magnitude of favorable new discoveries. In the meantime, antiviral chemotherapy, chemotherapy/prophylactic vaccination, and short interfering RNA silencing are worthy of intense investigation.


title: Community-acquired pneumonia in children.

text: PURPOSE OF REVIEW This review highlights recent developments in the diagnosis, etiology, therapy, and prevention of community-acquired pneumonia in children. RECENT FINDINGS Sensitive new diagnostic methods have increased the detection rate of the causative agent up to 94%. Streptococcus pneumoniae is the most prevalent bacterial pathogen in all ages. Polymerase chain reaction is a rapid and sensitive method for the detection of Chlamydia pneumoniae and Mycoplasma pneumoniae, which have gained greater importance in recent years. During the period covered by this review, two new agents causing pneumonia were extensively studied. Human metapneumonovirus detected in young children is a leading cause of respiratory disease during the first years of life. A novel coronavirus was identified as the causative agent of severe respiratory syndrome, a new respiratory illness that affects adults and children. One multicenter trial concluded that nonsevere pneumonia can be treated with a short course of oral amoxicillin and a multicenter international study showed that children with severe pneumonia have similar outcomes whether treated with oral amoxicillin or parenteral penicillin, but more data are needed to demonstrate the safety and efficacy of such regimens. SUMMARY The continued evolution of bacterial resistance highlights the need for appropriate use of antibacterials. Improved diagnostic techniques will aid the treatment of children with community-acquired pneumonia. Aggressive vaccination with the pneumococcal conjugate vaccine and other available vaccines as well as the development of new vaccines will aid the prevention of respiratory disease in children.


title: [Study on the dynamic prevalence of serum antibody against severe acute respiratory syndrome coronavirus in employees from wild animal market in Guangzhou].

text: OBJECTIVE To investigate the dynamic trend of specific antibody against severe acute respiratory syndrome (SARS)-CoV in serum collected at various periods among employees in Guangzhou Xinyuan animal market. METHODS Volunteers from employees of the animal market were recruited and their serum specific antibody against SARS-CoV were determined by enzyme linked immunesorbent assay (ELISA) method. RESULTS Positive SARS-CoV specific IgG antibody was found 25.61% (n = 328), 13.03% (n = 238), 12.59% (n = 135), 5.04% (n = 139) and 9.43% (n = 53) among volunteers, which were sampled in May 2003, Dec. 2003, Jan. 2004, July 2004 and June 2005 respectively. No specific IgM antibody was found in all of those samples. Among 129 samples which were tested twice or more, 97 were all negative, 18 all positive, 13 changed from positive to negative but only one sample from negative to positive. When the volunteers were divided by the duration of their working experiences as short-term or long-term, those who had worked at animal market for less than or more then 6 months when being tested, the positive rate for long-term employees were relatively constant, however, all of the persons employed after January 2004, when the palm civets and raccoon dogs were culled from the market, were tested negative. CONCLUSION The prevalence of specific antibody against SARS-CoV in employees of the animal market were somehow related with the presence or absence of palm civet. No serum was tested positive for persons who were employed after palm civets and raccoon dogs were culled from market. This data indicated that the SARS-CoV might have been from the palm civets and raccoon dog, and the animal market seemed to serve as one of the sources of infection.


title: Acute Bronchitis.

text: Cough is the most common illness-related reason for ambulatory care visits in the United States. Acute bronchitis is a clinical diagnosis characterized by cough due to acute inflammation of the trachea and large airways without evidence of pneumonia. Pneumonia should be suspected in patients with tachypnea, tachycardia, dyspnea, or lung findings suggestive of pneumonia, and radiography is warranted. Pertussis should be suspected in patients with cough persisting for more than two weeks that is accompanied by symptoms such as paroxysmal cough, whooping cough, and post-tussive emesis, or recent pertussis exposure. The cough associated with acute bronchitis typically lasts about two to three weeks, and this should be emphasized with patients. Acute bronchitis is usually caused by viruses, and antibiotics are not indicated in patients without chronic lung disease. Antibiotics have been shown to provide only minimal benefit, reducing the cough or illness by about half a day, and have adverse effects, including allergic reactions, nausea and vomiting, and Clostridium difficile infection. Evaluation and treatment of bronchitis include ruling out secondary causes for cough, such as pneumonia; educating patients about the natural course of the disease; and recommending symptomatic treatment and avoidance of unnecessary antibiotic use. Strategies to reduce inappropriate antibiotic use include delayed prescriptions, patient education, and calling the infection a chest cold.


title: [Analysis of medication characteristics of traditional Chinese medicine in treating COVID-19 based on data mining].

text: OBJECTIVE To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19). METHODS We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed. RESULTS The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were Liquorice, Scutellariabaicalensis, Semen armeniacaeamarae, and Gypsum. The commonly used traditional formulations included Maxing Shigan decoction, Yin Qiao powder, and Xuanbai Chengqi decoction. The Chinese patent drugs included Angong Niuhuang pill, Xuebijing injection, and Lianhua Qingwen capsule. The most common paired medications were Ephedra and Semen armeniacaeamarae, Fructusforsythiae and Liquorice. Two core combinations and one novel formula were discovered in the study. CONCLUSIONS Yin Qiao powder and Huopo Xialing decoction are the basic formulations for Weifen syndrome of COVID-19. In addition, Maxing Shigan decoction, Liang Ge powder, Qingwen Baidu decoction and Da Yuan decoction are the basic formulations for Qifen syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.


title: Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4.

text: HIV-1 envelope glycoproteins (Env), expressed at the cell surface, induce apoptosis of uninfected CD4+ T cells, contributing to the development of AIDS. Here we demonstrate that, independently of HIV replication, transfected or HIV-infected cells that express Env induced autophagy and accumulation of Beclin 1 in uninfected CD4+ T lymphocytes via CXCR4. The same phenomena occurred in a T cell line and in transfected HEK.293 cells that expressed both wild-type CXCR4 and a truncated form of CD4 that is unable to bind the lymphocyte-specific protein kinase Lck. Env-mediated autophagy is required to trigger CD4+ T cell apoptosis since blockade of autophagy at different steps, by either drugs (3-methyladenine and bafilomycin A1) or siRNAs specific for Beclin 1/Atg6 and Atg7 genes, totally inhibited the apoptotic process. Furthermore, CD4+ T cells still underwent Env-mediated cell death with autophagic features when apoptosis was inhibited. These results suggest that HIV-infected cells can induce autophagy in bystander CD4+ T lymphocytes through contact of Env with CXCR4, leading to apoptotic cell death, a mechanism most likely contributing to immunodeficiency.


title: Autoimmune disease triggered by infection with alphaproteobacteria.

text: Despite having long been postulated, compelling evidence for the theory that microbial triggers drive autoimmunity has only recently been reported. A specific association between Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, and primary biliary cirrhosis (PBC) has been uncovered in patients with PBC. Notably, the association between Novosphingobium infection and PBC has been confirmed in a mouse model in which infection leads to the development of liver lesions resembling PBC concomitant with the production of anti-PDC-E2 antibodies that cross-react with conserved PDC-E2 epitopes shared by Novosphingobium. The discovery of infectious triggers of autoimmunity is likely to change our current concepts about the etiology of various autoimmune syndromes and may suggest new and simpler ways to diagnose and treat these debilitating diseases.


title: Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate.

text: Development of vaccines for preventing a future pandemic of severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for biodefense preparedness is urgently needed. Our previous studies have shown that a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD) of SARS-CoV spike protein can induce potent neutralizing antibody responses and protection against SARS-CoV challenge in vaccinated animals. To optimize expression conditions for scale-up production of the RBD vaccine candidate, we hypothesized that this could be potentially achieved by removing glycosylation sites in the RBD protein. In this study, we constructed two RBD protein variants: 1) RBD193-WT (193-aa, residues 318-510) and its deglycosylated forms (RBD193-N1, RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318-536) and its deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were expressed as recombinant proteins in yeast. The purified recombinant proteins of these constructs were compared for their antigenicity, functionality and immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1 exhibited high expression yield, and maintained its antigenicity and functionality. More importantly, RBD219-N1 induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for further development.


title: The implementation of a standardized approach to laparoscopic rectal surgery.

text: BACKGROUND AND OBJECTIVES The purpose of this study was to audit our results after implementation of a standardized operative approach to laparoscopic surgery for rectal cancer within a fast-track recovery program. METHODS From January 2009 to February 2011, 100 consecutive patients underwent laparoscopic surgery on an intention-to-treat basis for rectal cancer. The results were retrospectively reviewed from a prospectively collected database. Operative steps and instrumentation for the procedure were standardized. A standard perioperative care plan was used. RESULTS The following procedures were performed: low anterior resection (n = 26), low anterior resection with loop-ileostomy (n = 39), Hartmann's operation (n = 14), and abdominoperineal resection (n = 21). The median length of hospital stay was 7 days; 9 patients were readmitted There were 9 cases of conversion to open surgery. The overall complication rate was 35%, including 6 cases (90/%) of anastomotic leakages requiring reoperation. The 30-day mortality was 5%. The median number of harvested lymph nodes was 15 (range, 2 to 48). There were 6 cases of positive circumferential resection margins. The median follow-up was 9 (range, 1 to 27) months. One patient with disseminated cancer developed port-site metastasis. CONCLUSIONS The results confirm the safety of a standardized approach, and the oncological outcomes are comparable to those of similar studies.


title: Respiratory syncytial virus infection in adults.

text: Respiratory syncytial virus (RSV) is now recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult community-acquired pneumonias. Attack rates in nursing homes are approximately 5 to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to 5%). Clinical features may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow transplant patients prior to marrow engraftment are at highest risk for pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably due to low viral titers in nasal secretions, but early bronchoscopy is valuable in immunosuppressed patients. Treatment of RSV in the elderly is largely supportive, whereas early therapy with ribavirin and intravenous gamma globulin is associated with improved survival in immunocompromised persons. An effective RSV vaccine has not yet been developed, and thus prevention of RSV infection is limited to standard infection control practices such as hand washing and the use of gowns and gloves.


Highly pathogenic avian flu, Japan.


Is SARS just ARDS?


title: A multiplex RT-PCR test for the differential identification of turkey astrovirus type 1, turkey astrovirus type 2, chicken astrovirus, avian nephritis virus, and avian rotavirus.

text: Recent studies have revealed the presence ofastroviruses and rotavirus in numerous poorly performing and healthy chicken and turkey flocks in the United States. The phylogenetic analysis of the sequence data produced during these studies has identified four groups of avian astroviruses circulating in the United States: turkey astrovirus types 1 and 2 (TAstV-1 and TAstV-2), avian nephritis virus (ANV), and a chicken-origin astrovirus (CAstV). As the molecular epidemiology of poultry enteric disease is poorly understood, the development of updated diagnostic assays is crucial to the continued surveillance and management of enteric disease in affected as well as healthy flocks. This report details the development of a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay specific for astroviruses and avian rotavirus in turkey-origin and chicken-origin samples. The assay consists of two multiplex tests, one for turkey-origin samples and one for chicken-origin samples. The turkey sample test differentially identifies TAstV-1, TAstV-2, ANV, and avian rotavirus. The test for chicken-origin samples differentially identifies CAstV, ANV, and avian rotavirus. Assay sensitivity varied by target sequence between approximately 10 copies for avian rotavirus alone and approximately 2 x 10(6) copies for TAstV-2 in the presence of a heterologous competitor RNA sequence. Each test was shown to be specific for the intended target by testing for cross-reaction with other common avian enteric viruses. The specificity was further shown by testing 109 chicken specimens and 32 turkey specimens from commercial flocks with the appropriate test and sequencing the RT-PCR amplicons to confirm amplification of the correct target.


title: [Thoracic high resolution CT findings of 100 SARS patients in convalescent period].

text: OBJECTIVE To study thoracic high resolution CT findings of severe acute respiratory syndrome (SARS) patients in convalescent period and the relationship between the features with laboratory and pulmonary function results. METHODS All the 100 SARS patients who had been discharged from hospital for about 2 months underwent thoracic high resolution CT examinations. Among them, 65 also had laboratory results and 91 underwent examinations of pulmonary function. RESULTS Forty-nine SARS patients (49.0%, 49/100) in convalescent period still had abnormal findings in CT examination. And ground-glass opacification (95.9%, 47/49) and reticular opacification (59.2%, 29/49) were common. There was no significant difference in the level of lymphocytes and CD4 cells among groups divided according to severity of CT findings (P > 0.01). Diffusing capacity for carbon monoxide (DLco%) of level 2 and 3 were statistically lower than that of level 0 (P < 0.01). CONCLUSIONS The features of CT findings of SARS patients in convalescent period are not the same as those of patients in period of apparent manifestation. The high resolution CT can reflect pulmonary diffusing function to some degree.


title: [SARS-CoV-2, a point in the storm].

text: Since its emergence in December 2019, scientific knowledge about the SARS-CoV-2 virus has evolved rapidly but, due to the complexity and novelty of this infection and its political and economic stakes, much remains to be clarified. Thousands of studies have already been published and scientific research is constantly evolving. In this multitude of information, we offer an update of the knowledge currently available. A limitation of the propagation, the understanding of the functioning of the virus and its clinical manifestations, the administration of specific treatments, rapid and reliable diagnostic tools are the basis of the fight against this germ, which is still little known today.


title: Syphilis in China: results of a national surveillance programme.

text: BACKGROUND After a massive syphilis epidemic in the first half of the 20th century, China was able to eliminate this infection for 20 years (1960-80). However, substantial changes in Chinese society have been followed by a resurgent epidemic of sexually transmitted diseases. Sporadic reports have provided clues to the magnitude of the spread of syphilis, but a national surveillance effort is needed to provide data for planning and intervention. METHODS We collected and assessed case report data from China's national sexually transmitted disease surveillance system and sentinel site network. FINDINGS In 1993, the reported total rate of cases of syphilis in China was 0.2 cases per 100,000, whereas primary and secondary syphilis alone represented 5.7 cases per 100,000 persons in 2005. The rate of congenital syphilis increased greatly with an average yearly rise of 71.9%, from 0.01 cases per 100,000 livebirths in 1991 to 19.68 cases per 100 000 livebirths in 2005. INTERPRETATION The results suggest that a range of unique biological and social forces are driving the spread of syphilis in China. A national campaign for detection and treatment of syphilis, and a credible prevention strategy, are urgently needed.


title: Bound for Sydney town: health surveillance on international cruise vessels visiting the Port of Sydney.

text: A program for routine health surveillance on international cruise ships visiting the Port of Sydney has been developed since 1998. Before introduction of this program, ships only reported quarantinable diseases and were not aware of the Australian requirement to report other infectious diseases. Voluntary routine reporting, developed in partnership with the cruise ship industry, provides timely information on all infectious diseases of public health interest during every cruise. During 1999-2003, the program resulted in detection of and response to 14 outbreaks of gastroenteritis or acute respiratory infection, affecting more than 1400 passengers and crew. The program has improved preventive action, and risk communication and management by cruise ship operators, and led to more timely investigation and support by public health authorities.


Summaries for patients. Do some patients with SARS have mild disease?


Disseminated adenovirus infection in a cat.


title: Infection of polarized epithelial cells with enteric and respiratory tract bovine coronaviruses and release of virus progeny.

text: OBJECTIVE To investigate the susceptibility of polarized epithelioid human rectal tumor (HRT-18G) cells to bovine coronaviruses (BCV) isolated from enteric (EBCV) and respiratory (RBCV) tract infections. PROCEDURE Cells of the G clone of HRT-18 were grown to confluent monolayers on permeable supports, and were directionally infected at the apical and basolateral domains with 3 wild-type BCV strains, RBCV-LSU-94LSS-051-2, RBCV-OK-0514-3, and EBCV-LY138-2, and 1 cell culture-adapted strain, EBCV-L9-80. Sequential cytopathic changes were microscopically monitored. Medium samples for titration of hemagglutinins and viral infectivity were collected directionally from both domains of the infected cell cultures at various intervals. RESULTS Polarized epithelioid HRT-18G cells from apical domains had maximal susceptibility to infection with the EBCV and RBCV strains, and those from basolateral surfaces had minimal susceptibility. Titers of hemagglutinins and infective progeny BCV reached 1,280 hemagglutinin units and 4.2 x 10(8) plaque-forming units/ml for apical samples, but were minimal for basolateral samples. Asymmetric virus release occurred through the apical surfaces of the HRT-18G cells by 12 hours after infection when cell fusion as a sign of cytopathic changes began. When cells were infected basolaterally, progeny virions released from apical surfaces reinfected the target cells from the apical domains and induced cytopathic changes were delayed about 12 hours, compared with changes detectable in apically exposed cultures. CONCLUSIONS EBCV and RBCV, isolated from cattle, had marked tropism for polarized epithelioid HRT-18G cells. Entry of BCV into the polarized HRT-18G cells was effected maximally through the apical domains and minimally through the basolateral domains. Release of progeny BCV occurred preferentially from the apical domains.


title: [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases].

text: OBJECTIVE To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS A retrospective analysis was performed for the clinical data of 115 children who were diagnosed with SARS-CoV-2 infection in the Wuhan Children's Hospital, including general information, history of close contact with individuals of SARS-CoV-2 infection, early clinical symptoms, laboratory examination results, and lung CT results. RESULTS Among the 115 children, there were 73 boys (63.5%) and 42 girls (36.5%), with a male/female ratio of 1:0.58. Of the 115 children, 105 (91.3%) had a definite history of close contact with individuals of SARS-CoV-2-infection. An increase in alanine aminotransferase was observed in 11 children (9.6%) and an increase in CK-MB was found in 34 children (29.6%). As for clinical symptoms, 29 children (25.2%) had fever, 47 (40.9%) had respiratory symptoms (including cough, rhinorrhea, and nasal congestion), and 61 (53.0%) were asymptomatic. Lung CT findings showed ground glass opacity, fiber opacities, patchy changes, and pulmonary consolidation in 49 children (42.6%), among whom 2 children had "white lung"; 39 children (33.9%) only had lung texture enhancement and 27 children (23.5%) had no pulmonary imaging changes. Among the 115 children, 3 were critically ill, among whom 1 had been cured and the other 2 were under continuous treatment. CONCLUSIONS Most of the children with SARS-CoV-2 infection have a close contact history. Critical cases are rare and there is a high proportion of asymptomatic infection.


title: Raising standards while watching the bottom line: making a business case for infection control.

text: While society would benefit from a reduced incidence of nosocomial infections, there is currently no direct reimbursement to hospitals for the purpose of infection control, which forces healthcare institutions to make economic decisions about funding infection control activities. Demonstrating value to administrators is an increasingly important function of the hospital epidemiologist because healthcare executives are faced with many demands and shrinking budgets. Aware of the difficulties that face local infection control programs, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors appointed a task force to draft this evidence-based guideline to assist hospital epidemiologists in justifying and expanding their programs. In Part 1, we describe the basic steps needed to complete a business-case analysis for an individual institution. A case study based on a representative infection control intervention is provided. In Part 2, we review important basic economic concepts and describe approaches that can be used to assess the financial impact of infection prevention, surveillance, and control interventions, as well as the attributable costs of specific healthcare-associated infections. Both parts of the guideline aim to provide the hospital epidemiologist, infection control professional, administrator, and researcher with the tools necessary to complete a thorough business-case analysis and to undertake an outcome study of a nosocomial infection or an infection control intervention.


title: Potential Treatments for COVID-19; a Narrative Literature Review.

text: SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11th. There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.


title: Coronavirus multiplication: locations of genes for virion proteins on the avian infectious bronchitis virus genome.

text: Six overlapping viral RNAs are synthesized in cells infected with the avian coronavirus infectious bronchitis virus (IBV). These RNAs contain a 3'-coterminal nested sequence set and were assumed to be viral mRNAs. The seven major IBV virion proteins are all produced by processing of three polypeptides of ca. 23, 51, and 115 kilodaltons. These are the core polypeptides of the small membrane proteins, the nucleocapsid protein, and the 155-kilodalton precursor to the large membrane proteins GP90 and GP84, respectively. To determine which mRNAs specify these polypeptides, we isolated RNA from infected cells and translated it in a messenger-dependent rabbit reticulocyte lysate. Proteins of 23, 51, and 110 kilodaltons were produced. Two-dimensional tryptic peptide mapping demonstrated that these proteins were closely related to the major virion proteins. Fractionation of the RNA before cell-free translation permitted the correlation of messenger activities for synthesis of the proteins with the presence of specific mRNAs. We found that the smallest RNA, RNA A, directs the synthesis of P51, the nucleocapsid protein. RNA C, which contains the sequences of RNA A, directs the synthesis of the small membrane protein P23. RNA E directs the synthesis of the large virion glycoproteins. These results supported a model in which only the unique 5'-terminal domain of each IBV mRNA is active in translation and enabled us to localize genes for virion proteins on the IBV genome.


title: Role of the stable signal peptide of Junín arenavirus envelope glycoprotein in pH-dependent membrane fusion.

text: The envelope glycoprotein of the arenaviruses (GP-C) is unusual in that the mature complex retains the cleaved, 58-amino-acid signal peptide. Association of this stable signal peptide (SSP) has been shown to be essential for intracellular trafficking and proteolytic maturation of the GP-C complex. We identify here a specific and previously unrecognized role of SSP in pH-dependent membrane fusion. Amino acid substitutions that alter the positive charge at lysine K33 in SSP affect the ability of GP-C to mediate cell-cell fusion and the threshold pH at which membrane fusion is triggered. Based on the presumed location of K33 at or near the luminal domain of SSP, we postulate that SSP interacts with the membrane-proximal or transmembrane regions of the G2 fusion protein. This unique organization of the GP-C complex may suggest novel strategies for intervention in arenavirus infection.


title: Single-Cell Studies of Phage λ: Hidden Treasures Under Occam's Rug.

text: Studies over more than half a century have resulted in what some consider a complete narrative for the life cycle of bacteriophage λ. However, this narrative is only complete within the limited resolution offered by the traditional genetic and biochemical approaches that were used to create it. A recent series of studies performed at the single-cell and single-phage levels has revealed a wealth of previously unknown features. By pointing to many open questions, these new studies highlight the limitations of our current understanding of λ, but they also initiate the process of forming a more detailed and quantitative narrative for the system.


title: [The use of genetic engineering in veterinary medicine with examples from epidemiology, diagnosis and drug production].

text: The results of genetic engineering have reached practical veterinary medicine already. Nevertheless there is a great lack of knowledge among those veterinarians who usually do not work with these methods. Therefore we want to give an introduction into the advantages and dangers of this technology concerning veterinary medicine. Some important analytical methods are explained. Related viruses such as WEE and EEE or canine parvovirus, feline parvovirus and mink enteritis virus, or the related coronaviruses FIPV and TGEV serve as examples for the possibilities in molecular diagnosis and epidemic monitoring. The history of the gl- mutants of PRV, now prescribed as vaccine strains in the FRG, is an example of the development of genetic engineered vaccines. A new generation of vaccines based on recombinant vaccinia viruses is imminent. Thus we have to be aware of the high risks and responsibility of everybody who is involved in these new systems, especially the scientist who produces genetically altered organisms.


Specific cleavage of 28S ribosomal RNA in murine coronavirus-infected cells.


title: Fatal 2009 pandemic influenza A (H1N1) in a bone marrow transplant recipient.

text: Conditions characterized by immunosuppression have been recently reported as risk factors for severe novel swine-origin influenza A (H1N1) virus (S-OIV) infection during the current 2009 pandemic. We report clinical and virological findings, antiviral therapy, and post-mortem study of S-OIV in an adult bone marrow transplant recipient. The viral genome was amplified by real time reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal swab specimen. The patient developed acute respiratory distress syndrome, septic shock, and eventually succumbed with a severe pulmonary haemorrhage. To the best of our knowledge, the entire clinical/therapy management and pathological examination in a transplant recipient infected with the S-OIV has not been previously documented. The fatal ending in this bone marrow transplant recipient supports recommendations that call for education measures, S-OIV vaccination, early diagnosis and aggressive treatment in the transplant population.


title: COVID-19 and Cancer Patients.

text: COVID-19 has now been declared a global pandemic with evolving incidence rates and fatalities. It is important to identify vulnerable populations who will be impacted most by this pandemic leading to higher mortality rates compared to the general healthy population. Although older patients and patients with co-morbidities fall into this vulnerable group, patients with hematologic and oncologic malignancies on active cytotoxic treatments are at even greater risk as they are both myelosuppressed and immunosuppressed. In addition to following the universal guidelines recommended by the Centers for Disease Control (CDC), it is important to also institute guidelines for cancer centers to help protect this vulnerable population. We review the current data, risks, and recommendations for COVID-19 in cancer patients.


title: Importance of primer selection in the application of PCR technology to the diagnosis of bovine leukemia virus.

text: The polymerase chain reaction (PCR) was used to detect bovine leukemia virus in bovine blood samples. When applied to leucocytes extracted from the blood samples, the standard method of DNA extraction gave good correlation with agar gel immunodiffusion, but a method in which 5 microliters of blood was the starting material was unreliable. Selection of the primers was important, and differences in results were observed when the PCR method was applied to blood samples from different geographic areas. The sensitivity varied from 50% to 90%, depending on the primer set applied to the gag gene of proviral nucleic acid. This variation was based on geographic origin of the cattle, suggesting an influence of viral strain. In some areas, more than 1 primer may needed to optimize results.


Peak expiratory flow (PEF) monitoring.


title: Gamma interferon-dependent, noncytolytic clearance of sindbis virus infection from neurons in vitro.

text: Due to the nonrenewable nature of neurons, recovery from viral infection of the central nervous system requires noncytopathic mechanisms for control of virus replication. Recovery from alphavirus encephalitis can occur without apparent neurological damage through the effects of antibody and gamma interferon (IFN-gamma). To establish an in vitro cell culture system that will allow the study of mechanisms of IFN-gamma-mediated control of Sindbis virus (SINV) replication in neurons, we have characterized the susceptibility to SINV infection and IFN-gamma responsiveness of two neuronal cell lines that can be differentiated in vitro: CSM14.1, a rat nigral cell line, and NSC34, a mouse motor neuron cell line. Undifferentiated CSM14.1 and NSC34 cells were permissive for SINV and susceptible to virus-induced cell death. With differentiation, CSM14.1 cells reduced virus replication and became progressively resistant to virus-induced cell death, resulting in prolonged virus replication. NSC34 cells did not differentiate completely and became only partially resistant to SINV infection. Both CSM14.1 and NSC34 cells responded to pretreatment with IFN-gamma by decreasing SINV replication. Differentiated CSM14.1 cells treated 24 h after infection with IFN-gamma responded with increased cell viability and clearance of infectious virus. IFN-gamma treatment sequentially altered the ratio of genomic to subgenomic viral RNA synthesis, promoted recovery of cellular protein synthesis, reduced viral protein synthesis, and inhibited viral RNA transcription within 24 h after treatment. We conclude that CSM14.1 cells provide an excellent model for the study of IFN-gamma-mediated noncytolytic clearance of SINV from mature neurons.


title: [Detection and clinical study on coronavirus HKU1 with acute lower respiratory tract infections of hospitalized children in Changsha].

text: OBJECTIVE In order to understand the epidemiological and virologic characteristics of coronavirus HKU1 infection in hospitalized children with acute respiratory tract infection (ARTI) in Changsha. METHODS 1165 nasopharyngeal aspirates (NPA) specimens were collected from hospitalized children with ARTI between September 2007 and August 2008 in Changsha. Specimens were screened for pol gene of coronavirus HKU1 by polymerase chain reaction. All positive amplification products were confirmed by sequencing and compared with those in GenBank. RESULTS Coronavirus HKU1 were detected in 12 patients (1.03%) out of the 1165 children. The patients were from 8 days to 3 years. The most common clinical diagnosis was bronchopneumonia(83.33%). Similarity of coronavirus HKU1 with those published in the GenBank at nucleotide levels was 98.18% - 100%. CONCLUSION Coronavirus HKU1 may be important pathogens in children with acute lower respiratory tract infection. Coronavirus HKU1 infections are common in children under 3 years old. There is no significant difference in the infectious rate between the boys and the girls. The peak of its prevalence is in spring and winter. A single genetic lineage of Coronavirus HKU1 was revealed in human subjects in Changsha.


title: CORD-19: The Covid-19 Open Research Dataset.

text: The Covid-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on Covid-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 75K times and has served as the basis of many Covid-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and preview tools and upcoming shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for Covid-19.


title: Molecular cloning of complementary DNA from a pneumopathic strain of bovine viral diarrhea virus and its diagnostic application.

text: A pneumopathic strain of bovine viral diarrhea virus was grown in cell culture and purified. Genomic ribonucleic acid was extracted, polyadenylated at the 3' end, and copied into complementary DNA after oligo-dT priming. Complementary DNA was male double stranded and cloned into the pUC9 plasmid. Approximately 200 complementary DNA clones varying in length from 0.5 to 2.5 kilobases were obtained. Hybridization assays indicated that the sequences isolated were specific for bovine viral diarrhea virus and that at least 5.5 kilobases of bovine viral diarrhea virus genome was represented in the library of complementary DNA clones, the majority of which may have originated from the 3' end of the virus genome. One cloned complementary DNA sequence was used as a 32P-labelled hybridization probe for bovine viral diarrhea virus detection. The probe hybridized with all cytopathic and noncytopathic strains of bovine viral diarrhea virus tested and was 100 times more sensitive than infectivity assays for the detection of bovine viral diarrhea virus. Hybridization did not occur with nucleic acids from bovine coronavirus, bluetongue virus, bovine adenovirus or uninfected cell cultures. Native plasmid DNA sequences, labelled with 32P, did not hybridize with bovine viral diarrhea virus ribonucleic acid.


title: Analysis of serum cytokines in patients with severe acute respiratory syndrome.

text: Severe acute respiratory syndrome (SARS) is an acute infectious disease of the respiratory system. Although a novel coronavirus has been identified as the causative agent of SARS, the pathogenic mechanisms of SARS are not understood. In this study, sera were collected from healthy donors, patients with SARS, patients with severe SARS, and patients with SARS in convalescence. The serum concentrations of interleukin-1 (IL-1), IL-4, IL-6, IL-8, IL-10, tumor growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-alpha were not significantly different in different groups. The IL-6 concentration was increased in SARS patients and was significantly elevated in severe SARS patients, but the IL-6 concentrations were similar in convalescent patients and control subjects, suggesting that there was a positive relationship between the serum IL-6 concentration and SARS severity. The concentrations of IL-8 and TGF-beta were decreased in SARS patients and significantly reduced in severe SARS patients, but they were comparable in convalescent SARS patients and control subjects, suggesting that there was a negative relationship between the IL-8 and TGF-beta concentrations and SARS severity. The concentrations of IFN-gamma, IL-4, and IL-10 showed significant changes only in convalescent SARS patients. The IFN-gamma and IL-4 levels were decreased, while the levels of IL-10 were increased, and the differences between convalescent SARS patients and other patient groups were statistically significant. These results suggest that there are different immunoregulatory events during and after SARS and may contribute to our understanding of the pathogenesis of this syndrome.


title: Eastern Mediterranean Health Journal (EMHJ): a 20-year overview (1995-2014).

text: The EMHJ was established in 1995 to provide a peer-reviewed platform for health professionals to share their research with the scientific community. The objective of this review was to examine EMR public health research trends, as reflected by EMHJ publications in 20 years (1995-2014), through secondary data analysis. Published articles were categorized according to EMR strategic priority areas (93%), i.e. health systems strengthening (25%); reproductive and child health (22%); communicable diseases (26%); noncommunicable diseases (25%); emergency preparedness (1.5%). Most papers were original research articles (85 %), published in English (94 %), but just over half (52 %) mentioned obtaining a form of ethical clearance in the text. Six countries had each over 100 papers published during the study period, i.e. Iran, Egypt, Saudi Arabia, Jordan, Iraq, Pakistan. Half EMHJ publications during this period came from 4 countries only (Iran, Egypt, Saudi Arabia, Jordan), which calls for further study to evaluate why other EMR nations are less well represented and how to encourage greater contribution from them over the coming years.


title: Erratum: Dangerous liaisons: molecular basis for a syndemic relationship between Kaposi's sarcoma and P. falciparum malaria.

text: [This corrects the article on p. 35 in vol. 4, PMID: 23487416.].


title: Efficacy of VRD(Bortezomib, Lenalidomide, and Dexamethasone) Consolidation Therapy and Maintenance Therapy with Immunomodulatory Drugs(Thalidomide or Lenalidomide) after Autologous Peripheral Blood Stem Cell Transplantation in the Era of Bortezomib-Containing Induction Therapy-A Single Institution E

text: Autologous stem cell transplantation(ASCT)for newly-diagnosed multiple myeloma(NDMM)has underwent recent improvements in combination with novel agents-containing induction and post-ASCT therapy. Since the approval of bortezomib for NDMM in Japan, we conducted the following regimen(BD arm)in transplant-eligible patients with NDMM: BD (bortezomib and dexamethasone)induction, ASCT, VRD consolidation, and maintenance therapy with immunomodulatory drugs(IMIDs). The efficacy and safety of the BD arm were compared to those of patients treated with vincristine, doxorubicin, and dexamethasone(VAD)induction followed by ASCT(VAD arm)retrospectively. Thirty-three patients were treated with the BD arm, and 92 patients with the VAD arm. Thirty-one patients in the BD arm proceeded to ASCT. Thereafter, 23 and 17 patients received VRD consolidation and IMIDs maintenance therapy, respectively. The rates of complete response/Bvery good partial response after ASCT, consolidation, and maintenance therapy were 43%/61%, 76%/90% and 87%/93%, respectively. The response rates after ASCT did not differ between BD and VAD arms. The median PFS was 46.2 months(BD arm)and 30.6 months(VAD arm)(HR 0.48[0.27-0.85], p=0.0106). The median OS was not-reached(BD arm)and 90.6 months(VAD arm)(HR 0.21[0.05-0.87], p=0.0172). VRD consolidation and IMIDs maintenance therapies improved disease status after ASCT and prolonged PFS and OS.


title: Development of an interactive bioterrorism and emerging infections curriculum for medical students and internal medicine residents.

text: While awareness of bioterrorism threats and emerging infectious diseases has resulted in an increased sense of urgency to improve the knowledge base and response capability of physicians, few medical schools and residency programs have curricula in place to teach these concepts. Public health agencies are an essential component of a response to these types of emergencies. Public health education during medical school is usually limited to the non-clinical years. With collaboration from our local public health agency, the Emory University School of Medicine developed a curriculum in bioterrorism and emerging infections. By implementing this curriculum in the clinical years of medical school and residency programs, we seek to foster improved interactions between clinicians and their local public health agencies.


title: [Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases].

text: OBJECTIVE To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.


title: [Research on antibodies against BHV-1, BHV-2, BHV-4, BVD-MD virus, bovine adenovirus A and B, rotavirus and coronavirus in cattle in western Zaire: complementary results].

text: Two-hundred bovine sera from western Zaire were screened for antibodies to 8 viruses: BHV-1, BHV-2, BHV-4, BVD-MD virus, bovine adenovirus A and B, bovine rotavirus and bovine coronavirus. Positive sera were found to all these viruses. For animals whose origin was undoubted, the main features were the high prevalence of infections by rotavirus and BHV-4 and the low prevalence of infections by coronavirus and BVD-MD virus.


title: Emerging or re-emerging bacterial zoonoses: factors of emergence, surveillance and control.

text: Surveillance and control of emerging bacterial zoonoses is essential in order to prevent both human and animal deaths and to avoid potential economic disorders created by trade barriers or a ban on free circulation of human or animal populations. An increased risk of exposition to zoonotic agents, the breakdown of the host's defenses, the emergence of bacterial strains resistant to antibiotics and their widespread distribution as well as conjunctural causes associated with the action or inaction of man have been identified as the main factors leading to the emergence or re-emergence of bacterial zoonoses. After an in-depth review of these various factors, the present manuscript reviews the main components of detection and surveillance of emerging or re-emerging bacterial zoonoses. A description of the systems of control and the main obstacles to their success is also presented. Detection and surveillance of emerging zoonoses have greatly benefited from technical progress in diagnostics. The success of detection and control of emerging bacterial zoonoses is largely based on international solidarity and cooperation between countries.


Joint Meeting of the German Association of Endocrine Surgeons (CAEK) and the British Association of Endocrine and Thyroid Surgeons (BAETS).


title: Wound Center Without Walls: The New Model of Providing Care During the COVID-19 Pandemic.

text: The COVID-19 pandemic poses a major challenge in delivering care to wound patients. Due to multiple comorbidities, wound patients are at an increased risk for the most extreme complications of COVID-19 and providers must focus on reducing their exposure risk. The Federal, State, and local governments, as well as payers, have urged hospitals and providers to reduce utilization of nonessential health services, but they also have given more flexibility to shift the site of necessary care to lower risk environments. Providers must be prepared for disruption from this pandemic mode of health care for the next 18 months, at minimum. The wound provider must accept the new normal during the pandemic by adapting their care to meet the safety needs of the patient and the public. The Wound Center Without Walls is a strategy to untether wound care from a physical location and aggressively triage and provide care to patients with wounds across the spectrum of the health system utilizing technology and community-centered care.


title: G1 phase cell cycle arrest induced by SARS-CoV 3a protein via the cyclin D3/pRb pathway.

text: SARS-CoV 3a is a structural protein, mainly localizing to Golgi apparatus and co-localizing with SARS-CoV M in co-transfected cells. Here we observed that transient expression of 3a inhibited cell growth and prevented 5-bromodeoxyuridine incorporation, suggesting that 3a deregulated cell cycle progression. Cell cycle analysis demonstrated that 3a expression was associated with blockage of cell cycle progression at G1 phase in HEK 293, COS-7, and Vero cells 24-60 h after transfection. Mutation analysis of 3a revealed that C-terminal region (176 aa approximately 274 aa), including a potential calcium ATPase motif, was essential for induction of cell cycle arrest. Topological analysis showed that 3a predominantly located in Golgi apparatus, with its N-terminus residing in the lumen (Nlum) and C-terminus in the cytosol (Ccyt). Analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that 3a expression was correlated with a significant reduction of cyclin D3 level and phosphorylation of retinoblastoma (Rb) protein at Ser-795 and Ser-809/811, not with the expression of cyclin D1, D2, cdk4, and cdk6 in 293 cells. Increases in p53 phosphorylation on Ser-15 were observed in both SARS-CoV M and 3a transfected cells, suggesting that it might not correlate with the 3a-induced G0/G1 phase arrest. The reduction of cyclin D3 level and phosphorylation of Rb were further confirmed in SARS-CoV infected Vero cells. These results indicate that SARS-CoV 3a protein, through limiting the expression of cyclin D3, may inhibit Rb phosphorylation, which in turn leads to a block in the G1 phase of the cell cycle and an inhibition of cell proliferation.


title: Postoperative pain medication requirements in patients undergoing computer-assisted (“Robotic”) and standard laparoscopic procedures for newly diagnosed endometrial cancer.

text: PURPOSE Laparoscopy (LSC) offers superior patient outcomes compared to laparotomy. Small retrospective/prospective series have suggested robotics offers further reduction in postoperative pain and pain medication use compared to standard LSC. Our objective was to compare postoperative pain in patients undergoing robotically assisted (RBT) versus standard LSC for newly diagnosed endometrial cancer. METHODS All preoperative endometrial cancer cases scheduled for RBT and LSC from May 1, 2007 to June 9, 2010 were identified. For this analysis, we only included cases not requiring conversion to laparotomy. All patients were offered intravenous (IV) patient-controlled analgesia (PCA) postoperatively. Intraoperative equivalent fentanyl doses (IEFDs) and pain scores in the postanesthesia care unit (PACU) were assessed. RESULTS IV PCA was used in 206 RBTs (86 %) and 208 LSCs (88 %). Median IEFD was 425 μg for LSCs and 500 μg for RBTs (P = 0.03). Median pain scores on PACU arrival were similar in both groups. Median highest pain score was 5 for LSCs and 4 for RBTs (P = 0.007). Linear regression demonstrated that the IEFD was not correlated with the highest pain score (R = 0.09; P = 0.07). Fentanyl was used postoperatively in 196 of 206 RBTs (95 %) and 187 of 208 LSCs (90 %). The total fentanyl doses were 242.5 (range 0-2705) μg and 380 (range 0-2625) μg, respectively (P < 0.001). The median hourly fentanyl doses were 16.7 (range 0-122.5) μg and 23.5 (range 0-132.4) μg, respectively (P = 0.005). Simultaneous multiple regression analysis further demonstrated RBT was independently associated with a lower total fentanyl dose compared to LSC (P = 0.02). CONCLUSIONS RBT is independently associated with significantly lower postoperative pain and pain medication requirements compared to LSC. The amount of intraoperative fentanyl analgesia does not appear to correlate with postoperative pain.Endometrial cancer is the most common gynecologic malignancy in the United States, with an estimated 47,130 new cases in 2012.1 An estimated 287,100 women were diagnosed with endometrial cancer worldwide in 2008.2 Surgery is the primary treatment of choice for the majority of these women.3 The standard surgical approach has been total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging via laparotomy. Multiple retrospective series have shown that a less invasive surgical approach via laparoscopy (LSC) is feasible and safe, and also associated with improved perioperative outcomes compared to laparotomy in these patients.4 The Gynecologic Oncology Group (GOG) published results of the largest randomized trial (LAP2) comparing LSC to laparotomy in patients with newly diagnosed endometrial carcinoma in 2009.5,6 This landmark study essentially changed the accepted standard surgical approach in this group. Postoperative complications, median blood loss, and median length of stay (LOS), despite increased operative time, were significantly lower in LSC patients despite 25 % requiring conversion to laparotomy.5 The first 802 eligible patients randomized in LAP2 also participated in a quality-of-life (QOL) study. Within 6 weeks of surgery, patients assigned to LSC reported significantly better QOL on all scales other than fear of recurrence.6 Overall, during this 6-week postoperative period, patients assigned to LSC had superior QOL, fewer physical symptoms, less pain and pain-related interference with functioning, better physical functioning and emotional state, earlier resumption of normal activities, earlier return to work, and better body image compared to those assigned to laparotomy.6 Recurrence-free and overall survivals were the same in both groups.7 Multiple published retrospective series have shown possible benefits, such as reduced postoperative pain, using the robotic (RBT) platform compared to LSC or laparotomy in patients with endometrial cancer.8-11 In a randomized trial, LSC was found to be associated with less postoperative pain compared to vaginal approaches in patients undergoing hysterectomy for benign gynecologic disease.12 A small retrospective series reported further reductions in postoperative pain in patients who had undergone an RBT hysterectomy compared to a standard total LSC hysterectomy for benign indications.13 A recent cost analysis suggested that patients experienced less pain and required less pain medication use after RBT procedures compared to LSC for endometrial cancer.14 Based on these reports, we sought to analyze postoperative pain and the use of pain medication in patients undergoing RBT compared to standard transperitoneal LSC procedures for newly diagnosed endometrial cancer during a concurrent time period. Of note, current RBT surgery is not truly robotic in that it is not autonomous. A more appropriate term is “computer-assisted surgery,” but to satisfy current convention, we refer to it as “robotic surgery” in this manuscript.


The virus hunter.


title: Fatal toxoplasmosis in sand cats (Felis margarita).

text: The sand cat (Felis margarita) is a small-sized felid occurring in the United Arab Emirates (UAE). The sand cat captive-breeding program at the Breeding Centre for Endangered Arabian Wildlife in Sharjah, UAE, has until recently been severely compromised by very high newborn mortality rates. Two different pairs of sand cats gave birth, respectively, to one and two litters (with a total of eight kittens) between 1999 and 2006. Seven out of eight kittens died between the third and 21st wk of life. Toxoplasmosis was confirmed as the cause of death in these two litters. Adult cats had high antibody titers to Toxoplasma gondii before pregnancy, suggesting that maternal immunity did not protect the kittens against infection with T. gondii and that maternal immunity might not have prevented transplacental transmission of the parasite. This observation contrasts with what is seen in domestic cats. To date, this is the first report on confirmed fatal toxoplasmosis and prevalence of T. gondii in sand cats.