title: Characteristics, Treatment Outcomes and Role of Hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur City: An Epidemio-Clinical Study.

text: Purpose The present study was undertaken to investigate epidemiological distribution, clinical manifestation, co morbid status, treatment strategy and case fatality index of emerging COVID-19 infection at SMS Medical College Hospital, Jaipur, Rajasthan. It also evaluated efficacy of hydroxychloroquine (HCQ) in treatment of patients and risk of serious adverse outcomes in patients with COVID-19 in relation to their co morbid status. Materials and methods In an attempt to provide extensive information pertaining to epidemiological and clinical characteristics of COVID-19, the present study was undertaken on 522 patients. The patients were COVID-19 confirmed positive by genomic analysis through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at SMS Medical College and Attached Hospitals, Jaipur. The indoor admitted patient's information inclusive of demographic profile (age, sex, nationality, residence), date of confirmation for positive COVID-19 case, travel/ exposure history, date of recovery/ death, clinical features, co morbidities and treatment plan was recorded. A serial follow-up of recovered patients to evaluate infective period of the disease was also part of the study. Results A total of 522 patients of laboratory confirmed COVID-19 test by RT-PCR at SMS Hospitals, Jaipur were assessed. Among the confirmed cases, most of patients were young adult in the age group with mean age of 35.42 years. 22.41% patients were below 20 years of age, majority of patients (58.80%) were in the age range of 21 to 50 years and only 18.79% patient population was in the age range of above 50 years. Females (39.08%) were affected less than males (60.91%) with an average sex ratio of female: male being 0.64. Out of the total analyzed patients, only 24.32% patients were symptomatic, among them fever (55.90%), cough (52.75%), sore throat (49.60%) and shortness of breath (46.45%) were the most common presenting clinical manifestations while a few patients also had symptoms of headache (26.77%), chest pain (6.29%) and other symptoms (7.87%) like pain abdomen, fatigue, joints pain, altered sensorium etc. Most of symptomatic patients belonging to older age group. An average of 40.40% patient population of above 50 years of age, were symptomatic while none of the patients below 10 years of age were symptomatic. 13.98% patients had some or the other underlying co morbid disease. The most prevalent co morbidity was hypertension (42.46%) followed by Diabetes mellitus (39.72%), Old k-chest (20.54%), COPD/ Bronchial Asthma (16.43%), Coronary artery disease (13.69%), Chronic kidney disease (13.69%) and Valvular heart disease (6.84%) distributed in co morbid patients of COVID-19. 60.27% of patient population with underlying co morbid conditions were more prone to develop symptomatology complex as compared to that observed in patients with no co morbidity (18.42%). 116 patients had recovered with effective treatment till the date of data analysis. Time of recovery was counted from the date of positive report to 1st negative report of oropharyngeal sample by RT-PCR for COVID-19 with an average recovery time of 8.15 days. 23.27% patients recovered within 5 days, while 52.58% patients took about 6-10 days, 23.27% patients took 11-15 days and remaining 0.86% took more than 16 days to recover. In the present study 15 patients had died till analysis of data, among the deceased, 73.33% were above 50 year of age with a male preponderance (66.6%). Interestingly, all deceased (100%) had presented with clinical manifestations of COVID-19 and all had underlying multiple co morbid conditions. Majority of patients had early mortality after admission to hospital with two third death account in initial three days. Asymptomatic patients (cases) treated with HCQ recovered early (average recovery time =5.4 days) compared to asymptomatic patients who did not receive any treatment (control group) and had longer recovery time (average recovery time =7.6 days). Conclusion The varied spectra of COVID-19 mostly affects young adult age group (third to fifth decades of life). Interestingly, early age group was also affected in significant proportion when compared with similar data from other countries. It was observed that male population seemed to be was more prone to getting infected. Majority of COVID-19 positive patients (nearly three-fourth) were asymptomatic (mostly in young age range) at the time of diagnosis, which poses a major challenge for health care workers. Fever, cough, sore throat and shortness of breath were major symptoms that could be detected in such COVID-19 patients. Symptomatic clinical manifestations were more common in old age population. Infectivity was higher in patients that had underlying co morbid disease, especially in patients with multiple co morbid conditions. Symptomatic presentation of COVID-19 was observed to be higher in patients with co morbid disease. Average recovery time from COVID-19 was 8 days with effective treatment. Mortality in COVID-19 was higher in old age population, male gender, symptomatic and co morbid patients as compared to other similarly matched group. Most of mortality was noted within first few days of admission, suggestive of early mortality due to the primary disease process. Treatment with HCQ had early recovery without effectively influencing the overall mortality.


title: [Palliation in patients with severe COVID-19].

text: Coronavirus Disease 2019 (COVID-19) can cause severe respiratory failure and distressing symptoms including fever, cough, breathlessness and anxiety. Symptomatic (palliative) treatment is of fundamental importance both in conjuncture with life-sustaining interventions and in end of life care. Based on the evidence to date, there are several treatment options to consider for the relief of fever (acetaminophen, NSAID, oral glucocorticoids), cough (morphine), breathlessness (morphine, oxygen, fan), anxiety (benzodiazepines) and pain (NSAID, morphine). Top priorities include precautions to protect staff and people at-risk from infection and planning how to provide adequate treatment for each individual depending on setting, including palliative care.


title: A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues.

text: Accumulating evidence demonstrates that adult tissues contain a population of stem cells that express early developmental markers such as stage-specific embryonic antigen and transcription factors Oct-4 and Nanog. These are the markers characteristic for embryonic stem cells, epiblast stem cells and primordial germ cells. The presence of these stem cells in adult tissues including bone marrow, epidermis, bronchial epithelium, myocardium, pancreas and testes supports the concept that adult tissues contain some population of pluripotent stem cells that is deposited in embryogenesis during early gastrulation. In this review we will discuss these data and present a hypothesis that these cells could be direct descendants of the germ lineage. The germ lineage in order to pass genes on to the next generations creates soma and thus becomes a 'mother lineage' for all somatic cell lineages present in the adult body.


title: Construction of murine coronavirus mutants containing interspecies chimeric nucleocapsid proteins.

text: Targeted RNA recombination was used to construct mouse hepatitis virus (MHV) mutants containing chimeric nucleocapsid (N) protein genes in which segments of the bovine coronavirus N gene were substituted in place of their corresponding MHV sequences. This defined portions of the two N proteins that, despite evolutionary divergence, have remained functionally equivalent. These regions included most of the centrally located RNA-binding domain and two putative spacers that link the three domains of the N protein. By contrast, the amino terminus of N, the acidic carboxy-terminal domain, and a serine- and arginine-rich segment of the central domain could not be transferred from bovine coronavirus to MHV, presumably because these parts of the molecule participate in protein-protein interactions that are specific for each virus (or, possibly, each host). Our results demonstrate that targeted recombination can be used to make extensive substitutions in the coronavirus genome and can generate recombinants that could not otherwise be made between two viruses separated by a species barrier. The implications of these findings for N protein structure and function as well as for coronavirus RNA recombination are discussed.


WHO Multicentre Collaborative Networks for Severe Acute Respiratory Syndrome (SARS) diagnosis.


title: Big Data and the Global Public Health Intelligence Network (GPHIN).

text: Background Globalization and the potential for rapid spread of emerging infectious diseases have heightened the need for ongoing surveillance and early detection. The Global Public Health Intelligence Network (GPHIN) was established to increase situational awareness and capacity for the early detection of emerging public health events. Objective To describe how the GPHIN has used Big Data as an effective early detection technique for infectious disease outbreaks worldwide and to identify potential future directions for the GPHIN. Findings Every day the GPHIN analyzes over more than 20,000 online news reports (over 30,000 sources) in nine languages worldwide. A web-based program aggregates data based on an algorithm that provides potential signals of emerging public health events which are then reviewed by a multilingual, multidisciplinary team. An alert is sent out if a potential risk is identified. This process proved useful during the Severe Acute Respiratory Syndrome (SARS) outbreak and was adopted shortly after by a number of countries to meet new International Health Regulations that require each country to have the capacity for early detection and reporting. The GPHIN identified the early SARS outbreak in China, was credited with the first alert on MERS-CoV and has played a significant role in the monitoring of the Ebola outbreak in West Africa. Future developments are being considered to advance the GPHIN's capacity in light of other Big Data sources such as social media and its analytical capacity in terms of algorithm development. Conclusion The GPHIN's early adoption of Big Data has increased global capacity to detect international infectious disease outbreaks and other public health events. Integration of additional Big Data sources and advances in analytical capacity could further strengthen the GPHIN's capability for timely detection and early warning.


title: The adaptive value of parental responsiveness to nestling begging.

text: Despite extensive theoretical and empirical research into offspring food solicitation behaviour as a model for parent-offspring conflict and communication, the adaptive value of parental responsiveness to begging has never been tested experimentally. Game theory models, as well as empirical studies, suggest that begging conveys information on offspring state, which implies that parental investment can be better translated to fitness by responding to begging when allocating resources rather than by ignoring it. However, this assumption and its underlying mechanisms have received little or no attention. Here we show by experiments with hand-raised house sparrow (Passer domesticus) nestlings that a 'responsive parent' will do better than a hypothetical 'non-responsive' mutant (that provides similar food amounts, but irrespective of begging). This is neither because food-deprived nestlings convert food to mass more efficiently, however, nor because responsiveness reduces costly begging. Rather, responsiveness to begging is adaptive because it reduces two opposing risks: one is wasting time when returning too soon to feed already satiated nestlings and the other is repeatedly overlooking some nestlings as a result of the stochastic nature of a random, non-responsive strategy. This study provides the first experimental evidence for the adaptive value of parental responsiveness to offspring begging.


title: pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several putative viral envelope proteins, including the spike (S), membrane (M), and small envelope (E) glycoproteins. Although these proteins likely are essential for viral replication, their specific roles in SARS-CoV entry have not been defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral entry through pH-dependent endocytosis. Further, we define its cellular tropism and demonstrate that virus transmission occurs through cell-mediated transfer by dendritic cells. The S glycoprotein was used successfully to pseudotype replication-defective retroviral and lentiviral vectors that readily infected Vero cells as well as primary pulmonary and renal epithelial cells from human, nonhuman primate, and, to a lesser extent, feline species. The tropism of this reporter virus was similar to that of wild-type, replication-competent SARS-CoV, and binding of purified S to susceptible target cells was demonstrated by flow cytometry. Although myeloid dendritic cells were able to interact with S and to bind virus, these cells could not be infected by SARS-CoV. However, these cells were able to transfer the virus to susceptible target cells through a synapse-like structure. Both cell-mediated infection and direct infection were inhibited by anti-S antisera, indicating that strategies directed toward this gene product are likely to confer a therapeutic benefit for antiviral drugs or the development of a SARS vaccine.


title: Detection by radioimmunoassay and enzyme-linked immunosorbent assay of coronavirus antibodies in bovine serum and lacteal secretions.

text: The sensitivity of a radioimmunoassay (RIA), an enzyme-linked immunosorbent assay (ELISA), and a serum neutralization assay (SN) for detecting antibodies to bovine coronavirus in serum and colostrum were compared. Although there proved to be a good correlation among all three assays (r = 0.915 and 0.964 for RIA with SN and ELISA, respectively), RIA and ELISA proved to be at least 10 times more sensitive than neutralization tests. By using these techniques, it was possible to detect a time-dependent decrease in antibody levels in bovine colostrum after parturition. Using ELISA, we demonstrated that 12 of 12 herds in Saskatchewan, and 109 of 110 animals tested, and antibody to bovine coronavirus. There was no elevated antibody response in serum or lacteal secretions of cows vaccinated once or twice with a commercially available modified live rota-coronavirus vaccine. In addition to being more sensitive than SN, ELISA and RIA proved to have other advantages for measuring antibody levels to bovine coronavirus and therefore warrant wider use as tools in diagnostic virology.


Using videotaped vignettes to teach medical students to perform the neurologic examination.


Indirubin-3'-oxime as an antiviral and immunomodulatory agent in treatment of severe human influenza virus infection.


title: Pathological and microbiological observations made on spontaneous cases of acute neonatal calf diarrhea.

text: The purpose of this report is to describe clinical signs, gross and microscopic lesions, bacteriological and immunofluorescence observations made on spontaneous cases of acute neonatal calf diarrhea (NCD) in dairy and beef herds. The following diagnostic tools were used: 1) direct smears of intestinal content, 2) Escherichia coli counts, 3) aerobic bacterial cultures of the small intestine and other organs (The O serogroup and the enterotoxigenicity of the E. coli isolated was determined), 4) detection of the two Nebraska NCD viruses (reo-like and corona-like) by the fluorescent antibody technique and 5) histological examination on different segments of the digestive tract. The following etiological diagnoses were suggested after post mortem examination of 55 cases of NDC (34 were submitted alive): reo-like virus only (1), reo-like virus + E. coli (4), reo-like virus + cryptosporidium (2), reo- + corona-like viruses (5), reo- + corona-like viruses + cryptosporidium (3), reo- + corona-like viruses + infectious bovine rhinotracheitis virus (1), coronavirus-like agent only (2), coronavirus-like agent + mycotic abomasitis (1), coronavirus-like agent + crytosporidium (1), E. coli only (6), cryptosporidium only (5), mycotic abomasitis (3), mycotic rumenitis + reticulitis (1) and undetermined (20). Most of the calves in the last group were submitted dead.


title: Acute eosinophilic pneumonia among US Military personnel deployed in or near Iraq.

text: CONTEXT Acute eosinophilic pneumonia (AEP) is a rare disease of unknown etiology characterized by respiratory failure, radiographic infiltrates, and eosinophilic infiltration of the lung. OBJECTIVES To describe a case series of AEP, illustrate the clinical features of this syndrome, and report the results of an epidemiologic investigation. DESIGN, SETTING, AND PARTICIPANTS Epidemiologic investigation of cases of AEP identified both retrospectively and prospectively from March 2003 through March 2004 among US military personnel deployed in or near Iraq. Survivors were offered a follow-up evaluation. MAIN OUTCOME MEASURE Morbidity and mortality related to AEP. RESULTS There were 18 cases of AEP identified among 183,000 military personnel deployed in or near Iraq during the study period, yielding an AEP incidence of 9.1 per 100,000 person-years (95% confidence interval, 4.3-13.3). The majority of patients (89%) were men and the median age was 22 (range, 19-47) years. All patients used tobacco, with 78% recently beginning to smoke. All but 1 reported significant exposure to fine airborne sand or dust. Known causes of pulmonary eosinophilia (eg, drug exposures or parasitic disease) were not identified. Epidemiologic investigation revealed no evidence of a common source exposure, temporal or geographic clustering, person-to-person transmission, or an association with recent vaccination. Six patients underwent bronchoalveolar lavage (median eosinophilia of 40.5%). All patients developed peripheral eosinophilia (range, 8%-42%). Mechanical ventilation was required in 67% for a median of 7 (range, 2-16) days. Two soldiers died; the remainder responded to corticosteroids and/or supportive care. Twelve individuals were reevaluated a median of 3 months after diagnosis. At that point, 3 patients reported mild dyspnea and 1 reported wheezing. All patients had finished treatment and had either normal or nearly normal spirometry results. None had recurrent eosinophilia. CONCLUSIONS AEP occurred at an increased rate among this deployed military population and resulted in 2 deaths. Failure to consider AEP in the differential diagnosis of respiratory failure in military personnel can result in missing this syndrome and possibly death. The etiology of AEP remains unclear, but the association with new-onset smoking suggests a possible link.


title: Characterization of functional domains in the human coronavirus HCV 229E receptor.

text: Human aminopeptidase N (hAPN or CD13) and porcine aminopeptidase N (pAPN) are functional receptors for human coronavirus (HCV) 229E and porcine transmissible gastroenteritis virus (TGEV), respectively. However, hAPN cannot function as a receptor for TGEV and pAPN cannot function as a receptor for HCV 229E. In this study, we constructed a series of chimeric hAPN/pAPN genes and expressed the corresponding proteins in transfected cells. Subsequently, we identified the chimeric proteins that can function as a receptor for HCV 229E. The results show that replacement of a small region of pAPN sequence (pAPN amino acids 255-348) with the corresponding hAPN sequence (hAPN amino acids 260-353) converts pAPN into a functional receptor for HCV 229E. The region of hAPN that we have defined in this way does not correspond to the region of pAPN that has been identified as essential for the TGEV-receptor interaction. We conclude that although both viruses use a homologous receptor protein, different regions of the protein are required to mediate susceptibility to infection with HCV 229E and TGEV.


title: [Clinical characteristics of human bocavirus infection in 90 children].

text: OBJECTIVE To study the clinical characteristics of human bocavirus (HBoV) infection in children. METHODS Nasal and throat swab samples were collected in 843 children with lower respiratory tract infection. The multiple RT-PCR method was used to detect HBoV and six other common respiratory tract viruses. The clinical characteristics of HboV positive cases were investigated. RESULTS Among 843 cases, 90 were HboV positive (10.7%), 131 were respiratory syncytial virus (RSV) positive (15.5%), 117 were influenza virus positive (13.9%), 84 were parainfluenza virus positive (10.0%), 55 were rhinovirus positive (6.5%), 48 were coronavirus positive (5.7%), and 33 were human metapneumovirus positive (3.7%). Of the 90 HBoV infected patients, 45 (50%) showed a co-infection with other respiratory tract viruses. Among them, 33 were infected with one other type of virus (37%), 11 (12%) were infected with two other types of virus, and 1 case (1%) was infected with other three viruses. The HBoV positive rate in children with wheezing was significantly higher than those without wheezing (17.0% vs 9.2%; P<0.01). The common clinical manifestations of HBoV-infected patients included frequent coughing, wheezing and fever. There were no significant differences in the frequency of wheezing between HBoV and RSV infected patients. CONCLUSIONS HBoV positive rate detected from children with wheezing is higher than from children without wheezing, suggesting that apart from RSV, HBoV is another virus causing wheezing in children with respiratory tract infection. Co-infections of HBoV with other respiratory track viruses can be present in some patients.


title: Lactogenic immunity to transmissible gastroenteritis (TGE) of swine induced by the attenuated Nouzilly strain of TGE virus: neutralizing antibody classes and protection.

text: An attenuated TGE coronavirus mutant (Nouzilly strain) relatively resistant to acidity and digestive enzymes was used for immunization of 11 seronegative pregnant sows, mainly by the oral route. Nouzilly strain is able to induce a protective lactogenic immunity in suckling piglets against severe virulent TGE challenge. However the level of neutralizing activity in serum and milk of vaccinated sows at the time of challenge exposure is not correlated with passive protection rate. Separation of the immunoglobulin classes bearing neutralizing activity in serum and milk from vaccinated sows, by ion-exchange chromatography, failed to demonstrate any relationship between antibody level of these fractions and passive protection rate of piglets. Our results suggest that IgA neutralizing antibodies present in milk are not the only parameters to consider to explain the lactogenic immunity induced by the Nouzilly strain given by oral route.


title: Laboratory and field evaluation of a new personal sampling system for assessing the protection provided by the N95 filtering facepiece respirators against particles.

text: OBJECTIVES We have recently developed a new personal sampling system for the real-time measurement of the protection provided by respirators against airborne dust and micro-organisms. The objective of this study was to evaluate the performance characteristics of the new sampling system in both laboratory and field conditions. METHODS The measurements were conducted using the N95 filtering facepiece respirators and the newly developed personal sampling system put on a manikin (laboratory study) or donned by a human subject (laboratory and field studies). Two inhalation flow rates (0 and 40 l min(-1)) in conjunction with the sampling flow rate (10 l min(-1)) were tested in the manikin-based experiments to investigate the effects of the leak location (nose, cheek and chin) and the depth of the sampling probe (0, 5, 10 and 15 mm) within the respirator. The effect of human activity on the protection factor was evaluated using a variety of head movements and breathing patterns when a human subject wore the respirator in a room-size laboratory test chamber. The field study was conducted during corn harvesting with a respirator worn by a human subject on a combine. RESULTS There was no significant difference in the protection factors for different leak locations, or for sampling probe depths, when the inhalation rate was 0 l min(-1). For the inhalation rate of 40 l min(-1), the protection factors for nose leaks were higher than those for chin and cheek leaks. Furthermore, the protection factor was the lowest and showed the least variation when the sampling probe depth was equal to 0 mm (imbedded on the respirator surface). Human subject testing showed that the grimace maneuver decreased the protection factor and changed the original respirator fit. The protection factor during breath holding was lower than that found during inhalation and exhalation. Field results showed greater variation than laboratory results. CONCLUSIONS The newly designed personal sampling system efficiently detected the changes in protection factors in real time. The sampling flow was least affected by the inhalation flow when the sampling probe was imbedded on the respirator surface. Leak location, breathing patterns and exercises did affect the measurement of the protection factors obtained using an N95 filtering facepiece respirator. This can be attributed to the differences in the in-mask airflow dynamics contributed by the leak, filter material, sampling probe and inhalation. In future studies, it would be beneficial if the laboratory data could be integrated with the field database.


title: Current Issues of Gastroenterology in Indonesia.

text: Indonesia is one of the most populous developing countries in the world. Similar with other developing countries, Indonesia has been suffered from the high incidence of gastroenterology diseases that mainly due to infection. In the recent years, Indonesia had also increased number of non-infectious gastroenterology diseases cases such as inflammatory bowel disease, gastroesophageal reflux disease, and colorectal cancer. Nevertheless, the developments of diagnostic and therapeutic modality along with the cooperation between sectors have undergone rapid progress as an effort in improving digestive health in Indonesia.


title: Assembly of coronavirus spike protein into trimers and its role in epitope expression.

text: The folding and oligomerization of coronavirus spike protein were explored using a panel of monoclonal antibodies. Chemical cross-linking and sedimentation experiments showed that the spike of transmissible gastroenteritis virus is a homotrimer of the S membrane glycoprotein. The spike protein was synthesized as a 175,000-apparent-molecular-weight (175K) monomer subunit that is sensitive to endo-beta-N-acetylglucosaminidase H. Assembly of monomers into a trimeric structure was found to occur on a partially trimmed polypeptide and to be a rate-limiting step, since large amounts of monomers failed to trimerize 1 h after completion of synthesis. Terminal glycosylation of newly assembled trimers, resulting in the biosynthesis of three 220K oligomers, occurred with a half time of approximately 20 min. Monomeric (230K to 240K) processed forms were also observed in cells and in virions. The 175K monomeric form expressed four major antigenic sites previously localized within the amino-terminal half of the S polypeptide chain; however, two classes of trimer-restricted epitopes (borne by three 220K and/or three 175K oligomers) were identified. The S glycoprotein of coronavirus might be a valuable model system for discovering new aspects of the maturation of membrane glycoproteins.


Considerations of Managing Lichen Planopilaris With Hydroxychloroquine During the COVID-19 Pandemic.


title: Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

text: 1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.


title: Six months results of laparoscopic sleeve gastrectomy in treatment of obesity and its metabolic complications.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has become a popular bariatric surgical procedure, with proven results in achieving weight loss, however data regarding its effectiveness on metabolic syndrome (MetS) components are scarce. The aims of the present study were to assess the outcomes of LSG on weight loss and obesity associated metabolic complications at six months following intervention. PATIENTS AND METHODS This was a retrospective study on 124 consecutive obese patients (29.8% men), who had undergone LSG between 01/01/2008 and 12/31/2010, in a highly specialized clinic. The dynamic of anthropometric and biochemical data between baseline and six months following LSG were evaluated. We also determined the change in MetS prevalence and used logistic regression to estimate predictors of MetS remission RESULTS 6 months after LSG, the body mass index (BMI) decreased from 46.84 +/- 8.62 to 33.81 +/- 7.04 kg/m2 (p < 0.001). Mean excess BMI loss (EBL) was 65.24 +/- 25.16%. The best results on weight loss were observed in young patients, not affected by MetS, with lower initial BMI. Lipids profile suffered a significant improvement (HDL cholesterol increased, while LDL, total cholesterol, triglycerides decreased, p < 0.05 for each). HOMA-IR values decreased by 75.2%, from 5.24 +/- 4.49 to 1.30 +/- 1.22 (p < 0.001). MetS prevalence was reduced from 74.3% to 18.4% (p < 0.001). In multivariate analysis, % EBL remained the only significant predictor of MetS remission, the risk for lack of a MetS remission being practically 3 times higher in patients with EBL < 50%, compared to those with EBL > 50% (OR: 2.97, CI: 1.1-10.23, p < 0.05). CONCLUSIONS As early as 6 months after LSG we recorded a significant weight loss and improvement in insulin resistance and lipids metabolism, as well as an impressive reduction in metabolic syndrome prevalence.


Fear of SARS thwarts medical education in Toronto.


WHO Framework Convention on Tobacco Control: development of an evidence based global public health treaty.


title: Cloning, expression, and sequence analysis of the ORF4 gene of the porcine reproductive and respiratory syndrome virus MN-1b.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) MN-1b strain open reading frame 4 (ORF4) has been cloned, sequenced, and expressed in Escherichia coli. The homologies of nucleotide and amino acid sequences between MN-1b (US isolate) and LV (European isolate) are 69% and 64%, respectively. The data also showed that ORF4 of MN-1b is 36 bases shorter than that of LV. Western blot analysis of expressed recombinant ORF4 protein reacted with 65% (26/40) of PRRSV-infected pig sera tested. These results demonstrated that ORF4 of PRRSV may not be a well-conserved region.


title: Smoking amidst the COVID-19 Pandemic - the invisible threat?

text: No abstract provided.


title: Sequencing arrays for screening multiple genes associated with early-onset human retinal degenerations on a high-throughput platform.

text: PURPOSE To develop and apply microarray-based resequencing technology to detect sequence alterations in multiple autosomal recessive retinal disease genes on a single high-throughput platform. METHODS Oligonucleotides corresponding to both strands of the target exons and the flanking intron sequences of 29,214 bp from 11 genes associated with autosomal recessive retinitis pigmentosa (arRP) were tiled on 20 x 25-microm microarrays (arRP-I arrays). A total of 155 exons were amplified from 35 arRP patient DNA samples, with each sample being sequenced on an arRP-I chip by hybridization. RESULTS With the arRP-I arrays, 97.6% of the tiled sequence were determined with more than 99% accuracy and reproducibility. Of the 2.4% unread sequence, 89.5% involved stretches of G or C. In analyzing the 903,140-bp sequence from the 35 patient samples, 506 sequence changes have been detected in which 386 are previously reported alterations, and 120 are novel. In addition to four known causative mutations, six novel sequence changes that are potentially pathogenic were observed. Additional analysis is needed to determine whether these changes are responsible for arRP in these patients. CONCLUSIONS The use of microarray for sequencing is a novel approach, and the arRP-I chip is the first successful application of this technology for determining sequence alteration in multiple disease-related genes. These arrays can be used for high-throughput genotyping of patients with relevant retinal conditions. In addition, these arrays offer a unique opportunity to interrogate complex patterns of inheritance due to the involvement of more than one gene by screening multiple genes on a single platform.


title: Preoperative embolization of carotid chemodectoma: a technical challenge that can be customized according to angioarchitecture. Illustrative cases.

text: Preoperative embolization of carotid paraganglioma is increasingly used to reduce the risk of surgical bleeding obtaining a more precise and extensive tumor resection. Currently the technique can be customized in consideration of the different tumor angioarchitecture, thanks to embolic materials with different vascular penetration: solid particles of polyvinyl-alcohol (PVA), histoacryl glue, and liquid polymer (Onyx(®)). Two cases of swelling dissection with volume progression over time came to our observation. Both patients (45 and 70-year-old women) were studied with neck ultrasound imaging and computed tomography (CT) and/or magnetic resonance (MR). In both cases the radiological investigations confirmed the clinical suspicion of carotid paraganglioma. Both patients were sent for angiography control and preoperative devascularization of the lesion. The treatment was performed under general anesthesia using, depending on the type of tumor vasculature, in case 1 solid particles of PVA and histoacryl glue, and in case 2 Onyx(®) (Covidien, Irvine). The patients successfully underwent excision of the lesion via cervicotomy within a week from the embolization procedure, without any complications. The histological findings confirmed the diagnosis of chemodectoma, and macrophage infiltrates were seen in the regions previously embolized. At one-year follow-up, there was no evidence of recurrent disease. The preoperative embolization of vascular lesions of the neck represents a safe technique that yields the best results when customized over the type of vascularization of the lesion, enabling the use of the most appropriate materials, depending on the case to be treated.


The mutation rate and variability of eukaryotic viruses: an analytical review.


title: Prophylactic efficacy of intranasal alpha 2-interferon against rhinovirus infections in the family setting.

text: In a double-blind evaluation of alpha 2-interferon as prophylaxis against naturally acquired respiratory infections, 120 adult members of 46 Australian families used 325 courses of intranasal spray during a six-month period, applying 5 million IU to the anterior nasal mucosa daily for seven days when respiratory symptoms developed in another member of the family. Used in this way, the alpha 2-interferon was well tolerated, and the rate of minor nasal bleeding (12 percent) did not increase with repeated courses. By comparison with the control group of 109 members of 49 families who used 319 seven-day courses of placebo spray, the users of alpha 2-interferon experienced 33 percent fewer days with nasal symptoms and 41 percent fewer episodes of "definite" respiratory illness. The users of alpha 2-interferon who were exposed to rhinovirus infections experienced 76 percent fewer days with symptoms and 86 percent fewer "definite" illnesses than their counterparts who used placebo. All of the observed clinical benefits, which suggested prevention of 6.8 "definite" respiratory illnesses per 100 courses of medication used, could be explained by a protective effect against illness associated with rhinoviruses that was not demonstrated for influenza A or B or coronavirus 229E.


title: Identification of the cis-acting signal for minus-strand RNA synthesis of a murine coronavirus: implications for the role of minus-strand RNA in RNA replication and transcription.

text: Minus-strand RNA is the first RNA species made by plus-strand RNA viruses, such as mouse hepatitis virus (MHV), and serves as a template for subsequent RNA replication and transcription. The regulation of minus-strand RNA synthesis has been difficult to study because of the paucity of minus-strand RNA. We have optimized a ribonuclease (RNase) protection assay which enabled the detection of minus-strand RNA synthesis from nonreplicating RNAs, thus clearly separating minus-strand from plus-strand RNA synthesis. We used an MHV defective interfering (DI) RNA containing a chloramphenicol acetyltransferase gene as a reporter to determine the cis-acting signal for MHV minus-strand RNA synthesis. It was found that minus-strand RNAs existed in double-stranded RNA form in the cell. By using various deletion clones, we demonstrated that the cis-acting signal for minus-strand RNA synthesis resides in the 55 nucleotides from the 3' end plus poly(A) tail of the MHV genome. This is much shorter than the 436 nucleotides previously reported for the 3'-end replication signal. No specific upstream MHV sequence was required for the initiation of minus-strand RNA synthesis. This finding suggests that the requirement for minus-strand RNA synthesis is much less stringent than that for genomic and subgenomic plus-strand RNA synthesis and that some of the minus-strand RNAs made may not be functional since they may lack the recognition signals for RNA replication or transcription. We further showed that the DI clones which actively transcribed a subgenomic mRNA from an internal intergenic sequence synthesized much less minus-strand RNA than those clones which did not transcribe subgenomic mRNAs, indicating that minus-strand RNA synthesis was inhibited by transcription from an internal promoter of the same DI RNA. This result also suggests that the regulation of the quantities of subgenomic mRNAs is not at the point of minus-strand RNA synthesis but rather at plus-strand RNA synthesis. Furthermore, the finding that the leader sequence was not required for minus-strand RNA synthesis suggests that the leader RNA regulates mRNA transcription during plus-strand RNA synthesis.


title: Robotic-assisted major pancreatic resection.

text: Robotic-assisted major pancreatic resections allow recreation of time-tested open surgical procedures on a minimally invasive platform. Early outcomes from robotic-assisted major pancreatic resections are comparable with those of laparoscopic and open approaches. Robotic assistance has the potential to bring the well-recognized advantages of minimally invasive surgery to major pancreatic resections. Technological innovations and increased surgeon familiarity with this approach will improve, likely leading to greater adoption and acceptance.


title: Epidemiology, clinical presentation and laboratory investigation of severe acute respiratory syndrome (SARS) in Canada, March 2003.

text: As of 23 March, 2003, 11 cases of SARS have been reported in Canada. Three patients had travelled to China, including Hong Kong SAR. The remaining eight had a history of close contact with cases. There have been three deaths. To date, evidence for human metapneumovirus has been found in six cases; further studies are ongoing to determine whether this virus is the causative agent of the SARS or whether other, so far undetected, pathogens are responsible. Public health measures are being implemented at the local, provincial, and national levels to identify new cases and prevent secondary transmission of SARS.


title: Causes of mortality and culling in adult pheasants.

text: The causes of the deaths or culling of 155 adult pheasants in breeding pens on one site between 1995 and 1997 were investigated. Approximately half the deaths were the result of problems associated with the reproductive tract or trauma, including injuries acquired during fighting or mating. Sinusitis was the commonest infectious cause of mortality or culling, despite medication of the flocks for mycoplasmosis. Marble spleen disease and pheasant coronavirus-associated nephritis, two viral conditions capable of causing high mortality, were diagnosed in a few birds in 1996 and 1997. Histomoniasis (blackhead) contributed to the mortality in 1996. A lymphomatous condition of uncertain aetiology was detected in a small number of birds.


title: Reliability of dual- vs single-volume reconstruction of three-dimensional digital subtraction angiography for follow-up evaluation of endovascularly treated intracranial aneurysms.

text: INTRODUCTION Single-volume reconstruction of three-dimensional (3D) digital subtraction angiography (DSA) can be effectively used for aneurysm assessment and planning of endovascular embolization. Unfortunately, post-embolization follow-up angiographic images can be obscured by artifact. The dual-volume reconstruction technique was developed in order to reduce artifact and enhance the visualization of the aneurysm, the parent vessel and side branches, and endovascular devices. The purpose of this study was to compare the reliability of dual- vs single-volume reconstruction of 3D DSA in evaluation of follow-up images after endovascular embolization of intracranial aneurysms. METHOD Four cerebrovascular neurosurgeons independently and blindly reviewed 20 randomly selected dual-and single-volume reconstructions of 3D DSAs demonstrating cerebral aneurysms treated with primary coil embolization, stent-assisted coil embolization, or Pipeline embolization. Five images were repeated for each modality (single and dual volume) in order to assess intra-rater reliability. The intraclass correlation coefficient was calculated as a measure of the overall inter-rater agreement. Cohen's kappa value was used to assess repeat measurement consistency for each rater. RESULTS Overall inter-rater agreement using dual- and single-volume reconstruction was 0.81 and 0.75, respectively. Dual-volume reconstruction resulted in superior agreement in assessing location, occlusion status, position of aneurysm recanalization or residual, status of nearby branches, presence of coil migration and presence of intravascular devices (stent or Pipeline). CONCLUSION Three-dimensional reconstruction is an important complementary imaging technique in evaluating the angioarchitecture of aneurysms and recanalization after endovascular embolization. Dual-volume reconstruction imaging was associated with superior inter- and intra-rater reliability.


title: In vivo induction of interferon-alpha in pig by non-infectious coronavirus: tissue localization and in situ phenotypic characterization of interferon-alpha-producing cells.

text: A low frequency peripheral blood mononuclear cell (PBMC) subpopulation, referred to as natural interferon-producing (NIP) cells, is described as producing interferon-alpha (IFN-alpha) following contact with non-infectious viral structures, namely viral glycoproteins. These cells are characterized in vitro as non-T, non-B, MHC class II+ and CD4+ cells. In this study, NIP cells were analysed in vivo after an intravenous injection of UV-inactivated transmissible gastroenteritis virus in newborn piglets, which resulted in strong serum IFN-alpha production. Splenocytes, but not PBMC, were the IFN-alpha producers in vivo. Using double immunohistochemical labelling for both IFN-alpha and leukocyte markers, we established that splenic NIP cells were not T or B cells. The majority were MHC class II+ and only a minority expressed a macrophage marker. NIP cells were localized in contact with MHC class II-expressing cells and T cells, which suggested that NIP cells might modulate the antiviral immune response.


title: Ocelots on Barro Colorado Island are infected with feline immunodeficiency virus but not other common feline and canine viruses.

text: Transmission of pathogens from domestic animals to wildlife populations (spill-over) has precipitated local wildlife extinctions in multiple geographic locations. Identifying such events before they cause population declines requires differentiating spillover from endemic disease, a challenge complicated by a lack of baseline data from wildlife populations that are isolated from domestic animals. We tested sera collected from 12 ocelots (Leopardus pardalis) native to Barro Colorado Island, Panama, which is free of domestic animals, for antibodies to feline herpes virus, feline calicivirus, feline corona virus, feline panleukopenia virus, canine distemper virus, and feline immunodeficiency virus (FIV), typically a species-specific infection. Samples also were tested for feline leukemia virus antigens. Positive tests results were only observed for FIV; 50% of the ocelots were positive. We hypothesize that isolation of this population has prevented introduction of pathogens typically attributed to contact with domestic animals. The high density of ocelots on Barro Colorado Island may contribute to a high prevalence of FIV infection, as would be expected with increased contact rates among conspecifics in a geographically restricted population.


title: Perforin and gamma interferon-mediated control of coronavirus central nervous system infection by CD8 T cells in the absence of CD4 T cells.

text: Infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus produces acute and chronic demyelination. The contributions of perforin-mediated cytolysis and gamma interferon (IFN-gamma) secretion by CD8(+) T cells to the control of infection and the induction of demyelination were examined by adoptive transfer into infected SCID recipients. Untreated SCID mice exhibited uncontrolled virus replication in all CNS cell types but had little or no demyelination. Memory CD8(+) T cells from syngeneic wild-type (wt), perforin-deficient, or IFN-gamma-deficient (GKO) donors all trafficked into the infected CNS in the absence of CD4(+) T cells and localized to similar areas. Although CD8(+) T cells from all three donors suppressed virus replication in the CNS, GKO CD8(+) T cells expressed the least antiviral activity. A distinct viral antigen distribution in specific CNS cell types revealed different mechanisms of viral control. While wt CD8(+) T cells inhibited virus replication in all CNS cell types, cytolytic activity in the absence of IFN-gamma suppressed the infection of astrocytes, but not oligodendroglia. In contrast, cells that secreted IFN-gamma but lacked cytolytic activity inhibited replication in oligodendroglia, but not astrocytes. Demyelination was most severe following viral control by wt CD8(+) T cells but was independent of macrophage infiltration. These data demonstrate the effective control of virus replication by CD8(+) T cells in the absence of CD4(+) T cells and support the necessity for the expression of distinct effector mechanisms in the control of viral replication in distinct CNS glial cell types.


title: Ethics and public health emergencies: restrictions on liberty.

text: Responses to public health emergencies can entail difficult decisions about restricting individual liberties to prevent the spread of disease. The quintessential example is quarantine. While isolating sick patients tends not to provoke much concern, quarantine of healthy people who only might be infected often is controversial. In fact, as the experience with severe acute respiratory syndrome (SARS) shows, the vast majority of those placed under quarantine typically don't become ill. Efforts to enforce involuntary quarantine through military or police powers also can backfire, stoking both panic and disease spread. Yet quarantine is part of a limited arsenal of options when effective treatment or prophylaxis is not available, and some evidence suggests it can be effective, especially when it is voluntary, home-based and accompanied by extensive outreach, communication and education efforts. Even assuming that quarantine is medically effective, however, it still must be ethically justified because it creates harms for many of those affected. Moreover, ethical principles of reciprocity, transparency, non-discrimination and accountability should guide any implementation of quarantine.


title: Avian influenza: the threat of the 21st century.

text: This study aimed to review the literature on infection with the H5N1 subtype of avian influenza A virus, taking into consideration the fact that, in the event of a pandemic, children might become a major risk group. Searches were limited to the past ten years and were carried out using the following electronic databases: Medline, MD Consult, HighWire and Medscape. Children and young adults account for a significant proportion of the susceptible population. We found that more than half of the individuals infected were under 20 years of age and that one quarter was under the age of 10. The incubation period ranged from 2 to 5 days. Initial clinical manifestations are nonspecific, which hinders the diagnosis. Most of the infected individuals presented severe pneumonia, which evolved to respiratory insufficiency within an average of 4 days. Chest X-rays can reveal diffuse multifocal/ interstitial infiltrates or segmental/lobar consolidation with air bronchogram. The pathogenic potential is high, with mortality rates up to 63%, indicating that the pandemic virus might present high pathogenicity and high mortality. Knowledge of the risk of a pandemic and of the measures to be taken in suspect cases constitutes an important step toward controlling a potential pandemic.


title: Evaluation of public health response to hurricanes finds North Carolina better prepared for public health emergencies.

text: Reviews of state public health preparedness improvements have been primarily limited to measuring funds expenditures and achievement of cooperative agreement benchmarks. Such reviews fail to assess states' actual capacity for meeting the challenges they may face during an emergency, as evidenced by activities undertaken during the various phases of a disaster. This article examines North Carolina's public health preparedness and response performance during two hurricanes, Hurricane Floyd in 1999 and Hurricane Isabel in 2003, as well as capacity building activities in the intervening years. North Carolina created new infrastructures, enhanced laboratory capacity, and strengthened communications after Hurricane Floyd. These activities facilitated implementation of functional capabilities through effective centralized communication, command and control incident management, and a rapid needs assessment and medical surveillance during Hurricane Isabel. North Carolina continues to implement these capabilities in public health emergencies. Measuring and implementing functional capabilities during exercises or real events facilitates achievement of preparedness performance standards, goals, and objectives.


title: Rubella virus nonstructural protein protease domains involved in trans- and cis-cleavage activities.

text: Rubella virus (RV) genomic RNA contains two large open reading frames (ORFs): a 5'-proximal ORF encoding nonstructural proteins (NSPs) that function primarily in viral RNA replication and a 3'-proximal ORF encoding the viral structural proteins. Proteolytic processing of the RV NSP ORF translation product p200 is essential for viral replication. Processing of p200 to two mature products (p150 and p90) in the order NH(2)-p150-p90-COOH is carried out by an RV-encoded protease residing in the C-terminal region of p150. The RV nonstructural protease (NS-pro) belongs to a viral papain-like protease family that cleaves the polyprotein both in trans and in cis. A conserved X domain of unknown function was found from previous sequence analysis to be associated with NS-pro. To define the domains responsible for cis- and trans-cleavage activities and the function of the X domain in terms of protease activity, an in vitro translation system was employed. We demonstrated that the NSP region from residue 920 to 1296 is necessary for trans-cleavage activity. The domain from residue 920 to 1020 is not required for cis-cleavage activity. The X domain located between residues 834 and 940, outside the regions responsible for both cis- and trans-cleavage activities of NS-pro, was found to be important for NS-pro trans-cleavage activity but not for cis-cleavage activity. Analysis of sequence homology and secondary structure of the RV NS-pro catalytic region reveals a folding structure similar to that of papain.


title: Streptozotocin is responsible for the induction and progression of renal tumorigenesis in diabetic Wistar-Furth rats treated with insulin or transplanted with agarose encapsulated porcine islets.

text: Streptozotocin (STZ), a nitrosourea with DNA alkylating properties, has been widely used to induce hyperglycemia by specifically destroying the insulin-producing β-cells of the islets of Langerhans in experimental models of Type I diabetes. STZ's known carcinogenic properties, however, raise concerns about its suitability for long-term studies. We conducted a formal study of STZ's carcinogenic effects in long-term surviving diabetic Wistar-Furth rats. To determine if insulin therapy or islet transplantation exacerbated tumorigenesis, rats were randomly assigned to one of four experimental groups: normal animals with no treatment (Group 1, n=12); normal animals that underwent peritoneal implantation of porcine islets encapsulated in a double layer of agarose to form islet macrobeads (normal + islets; group 2, n=12); STZ treatment followed by daily exogenous insulin (STZ + insulin; group 3, n=18) and STZ treatment followed by the intraperitoneal implantation of porcine islet macrobeads (STZ + islets; group 4, n=14). At 215 days post-STZ induction, no renal proliferative lesions were observed in animals that did not receive STZ (group 1 and group 2) whereas adenoma incidences of 57% for group 3 and 34% for group 4 were observed. By terminal necropsy at day 351, the incidence and severity of renal proliferative lesions increased with tubular carcinoma observed in 67% of group 3 and 60% of group 4 animals. We conclude that the STZ-induced diabetic rat model is not suitable for long-term studies because of progressive renal tumorigenesis. Our experiments also demonstrate the safety and effectiveness of porcine islet macrobeads for the treatment of diabetes.


Increasing epidemic surge capacity with home-based hospital care.


title: Quality management case studies in health service emergencies: SARS and wildland-urban interface fires.

text: The province of British Columbia, Canada, experienced 2 major health emergency situations during 2003: severe acute respiratory syndrome (SARS) in early 2003 and wildland-urban interface fires during the summer of 2003. The interface fires occurred within the boundaries of the Interior Health Authority, 1 of 5 health authorities responsible for the delivery of health services in their respective areas of the province. The British Columbia Center for Disease Control (BCCDC) managed the SARS crisis in the province. Both organizations subsequently conducted quality management reviews of their handling of these emergency situations. This article reports on the quality management review of health services delivery during the interface fires and explores the role of physicians during regional emergencies. A similar report was published in the Spring 2004 edition of Quality Management in Health Care on the way SARS was managed at the BCCDC. This article also compares managing a foreseeable emergency situation, such as a wildland-urban interface fire, with managing the unknown, which describes the situation during the initial stages of SARS. The realities confronting the unknown, and the need to manage the situation such that learning and discovery environments are allowed to come into being and evolve rapidly, are discussed.


title: Viral replicase gene products suffice for coronavirus discontinuous transcription.

text: We have used vaccinia virus as a vector to clone a 22.5-kbp cDNA that represents the 5' and 3' ends of the human coronavirus 229E (HCoV 229E) genome, the HCoV 229E replicase gene, and a single reporter gene (coding for green fluorescent protein [GFP]) located downstream of a regulatory element for coronavirus mRNA transcription. When RNA transcribed from this cDNA was transfected into BHK-21 cells, a small percentage of cells displayed strong fluorescence. A region of the mRNA encoding GFP was amplified by PCR and shown to have the unique mRNA leader-body junction indicative of coronavirus-mediated transcription. These data show that the coronavirus replicase gene products suffice for discontinuous subgenomic mRNA transcription.


History of respiratory medicine in Canada: a new Canadian Respiratory Journal series.


BAT RABIES.


title: Crystal structure of a monomeric form of severe acute respiratory syndrome coronavirus endonuclease nsp15 suggests a role for hexamerization as an allosteric switch.

text: Mature nonstructural protein-15 (nsp15) from the severe acute respiratory syndrome coronavirus (SARS-CoV) contains a novel uridylate-specific Mn2+-dependent endoribonuclease (NendoU). Structure studies of the full-length form of the obligate hexameric enzyme from two CoVs, SARS-CoV and murine hepatitis virus, and its monomeric homologue, XendoU from Xenopus laevis, combined with mutagenesis studies have implicated several residues in enzymatic activity and the N-terminal domain as the major determinant of hexamerization. However, the tight link between hexamerization and enzyme activity in NendoUs has remained an enigma. Here, we report the structure of a trimmed, monomeric form of SARS-CoV nsp15 (residues 28 to 335) determined to a resolution of 2.9 A. The catalytic loop (residues 234 to 249) with its two reactive histidines (His 234 and His 249) is dramatically flipped by approximately 120 degrees into the active site cleft. Furthermore, the catalytic nucleophile Lys 289 points in a diametrically opposite direction, a consequence of an outward displacement of the supporting loop (residues 276 to 295). In the full-length hexameric forms, these two loops are packed against each other and are stabilized by intimate intersubunit interactions. Our results support the hypothesis that absence of an adjacent monomer due to deletion of the hexamerization domain is the most likely cause for disruption of the active site, offering a structural basis for why only the hexameric form of this enzyme is active.


title: Myxoma virus and oncolytic virotherapy: a new biologic weapon in the war against cancer.

text: Oncolytic virotherapy is an innovative alternative to more conventional cancer therapies. The ability of some viruses to specifically target and kill malignant cancerous cells while leaving normal tissue unscathed has opened a large repertoire of new and selective cancer killing therapeutic candidates. Poxviruses, such as vaccinia virus, have a long history of use in humans as live vaccines and have more recently been studied as potential platforms for delivery of immunotherapeutics and attenuated variants of vaccinia have been explored as oncolytic candidates. In contrast, the poxvirus myxoma virus is a novel oncolytic candidate that has no history of use in humans directly, as it has a distinct and absolute host species tropism to lagomorphs (rabbits). Myxoma virus has been recently shown to be able to also selectively infect and kill human tumor cells, a unique tropism that is linked to dysregulated intracellular signalling pathways found in the majority of human cancers. This review outlines the existing knowledge on the tropism of myxoma virus for human cancer cells, as well as preclinical data exhibiting its ability to infect and clear tumors in animal models of cancer. This is an exciting new therapeutic option for treating cancer, and myxoma virus joins a growing group of oncolytic virus candidates that are being developed as a new class of cancer therapies in man.


Fatal flows--doctors on the move.


title: Development of a hyperimmune equine serum therapy for COVID-19 in Argentina.

text: The disease named COVID-19, caused by the SARS-CoV-2 coronavirus, is currently generating a global pandemic. Vaccine development is no doubt the best long-term immunological approach, but in the current epidemiologic and health emergency there is a need for rapid and effective solutions. Convalescent plasma is the only antibody-based therapy available for COVID-19 patients to date. Equine polyclonal antibodies (EpAbs) put forward a sound alternative. The new generation of processed and purified EpAbs containing highly purified F(ab')2 fragments demonstrated to be safe and well tolerated. EpAbs are easy to manufacture allowing a fast development and scaling up for a treatment. Based on these ideas, we present a new therapeutic product obtained after immunization of horses with the receptor-binding domain of the viral Spike glycoprotein. Our product shows around 50 times more potency in in vitro seroneutralization assays than the average of convalescent plasma. This result may allow us to test the safety and efficacy of this product in a phase 2/3 clinical trial to be conducted in July 2020 in the metropolitan area of Buenos Aires, Argentina.


title: SARS: mobilizing and maintaining a public health emergency response.

text: During the spring and summer of 2003, the Centers for Disease Control and Prevention (CDC) mobilized the resources of the entire agency in a concerted effort to meet the challenges posed by the outbreak of Severe Acute Respiratory Syndrome (SARS). Over the 133 days that comprised the emergency response phase of the SARS outbreak, CDC utilized the skills of more than 850 people. These staff were deployed from every Center, Institute, and Office within CDC and the Agency for Toxic Substances and Disease Registry. They provided technical assistance to countries reporting large numbers of cases and requesting assistance, met passengers and crew from these locations upon arrival in the United States, and assured that the syndrome was reported and thoroughly investigated within the United States. This paper describes the operational requirements that were established and the resources that were used to conduct this investigation.


title: Structural polypeptides of coronavirus IBV.

text: Avian infectious bronchitis virus (IBV) was grown and radiolabelled with 35S-methionine, 3H-leucine and 3H-glucosamine in de-embryonated chicken eggs. Approximately 12 different polypeptides were clearly detected by SDS-polyacrylamide gel electrophoresis of virus preparations. Growth of IBV in chorioallantoic membrane cells labelled with 35S-methionine indicated that most of these polypeptides, and additional ones, some of which were glycosylated, were host components. Five polypeptides appeared to be virus-coded, with apparent mol. wt. of 94 x 10(3), 84 x 10(3), 54 x 10(3), 30 x 10(3) and 28 x 10(3). Four of these, p94, p84, p30 and p28, were glycosylated. The virion spikes appeared to be composed of p94 and p84, while p30 and p28 were partially embedded in the virion membrane. By analogy with other reports, p54 is the nucleocapsid polypeptide.


title: Cryptogenic organizing pneumonia.

text: Organizing pneumonia (OP) is a pathological pattern defined by the characteristic presence of buds of granulation tissue within the lumen of distal pulmonary airspaces consisting of fibroblasts and myofibroblasts intermixed with loose connective matrix. This pattern is the hallmark of a clinical pathological entity, namely cryptogenic organizing pneumonia (COP) when no cause or etiologic context is found. The process of intraalveolar organization results from a sequence of alveolar injury, alveolar deposition of fibrin, and colonization of fibrin with proliferating fibroblasts. A tremendous challenge for research is represented by the analysis of features that differentiate the reversible process of OP from that of fibroblastic foci driving irreversible fibrosis in usual interstitial pneumonia because they may determine the different outcomes of COP and idiopathic pulmonary fibrosis (IPF), respectively. Three main imaging patterns of COP have been described: (1) multiple patchy alveolar opacities (typical pattern), (2) solitary focal nodule or mass (focal pattern), and (3) diffuse infiltrative opacities, although several other uncommon patterns have been reported, especially the reversed halo sign (atoll sign). Definitive diagnosis is based on (1) a suggestive clinical radiological presentation, (2) the demonstration of the characteristic pathological pattern at lung histopathology, and (3) exclusion of possible causes. Transbronchial biopsies or a transthoracic biopsy may also contribute to the pathological diagnosis. Rapid clinical and imaging improvement is obtained with corticosteroid therapy. Because of the risk of misdiagnosing alternative conditions that may mimic OP, only typical cases may be managed without histopathological confirmation, and patients should be followed with particular attention paid to any clue of alternate diagnosis, especially in case of incomplete response to treatment. Patients and clinicians must be aware of frequent relapses after stopping corticosteroid treatment.


title: Approaches to therapy of prion diseases.

text: Devising approaches to the therapy of transmissible spongiform encephalopathies, or prion diseases, is beset by many difficulties. For one, the nature of the infectious agent, the prion, is understood only in outline, and its composition, structure, and mode of replication are still shrouded in mystery. In addition, the mechanism of pathogenesis is not well understood. Because clinical disease affects mainly the brain parenchyme, therapeutic agents must be able to traverse the brain-blood barrier (BBB) or have to be introduced directly into the cerebrospinal fluid or brain tissue. And finally, because the disease is usually recognized only after onset of severe clinical symptoms, the question arises as to whether the neurodegenerative processes can be reversed to any extent after a successful eradication of the agent.


title: Monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute-phase sera of severe acute respiratory syndrome patients.

text: Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV) infection is a critical step in preventing another global outbreak. In this study, 829 serum specimens were collected from 643 patients initially reported to be infected with SARS-CoV. The sera were tested for the N protein of SARS-CoV by using an antigen capture enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies against the N protein of SARS-CoV and compared to 197 control serum samples from healthy donors and non-SARS febrile patients. The results of the N protein detection analysis were directly related to the serological analysis data. From 27 SARS patients who tested positive with the neutralization test, 100% of the 24 sera collected from 1 to 10 days after the onset of symptoms were positive for the N protein. N protein was not detected beyond day 11 in this group. The positive rates of N protein for sera collected at 1 to 5, 6 to 10, 11 to 15, and 16 to 20 days after the onset of symptoms for 414 samples from 298 serologically confirmed patients were 92.9, 69.8, 36.4, and 21.1%, respectively. For 294 sera from 248 serological test-negative patients, the rates were 25.6, 16.7, 9.3, and 0%, respectively. The N protein was not detected in 66 patients with cases of what was initially suspected to be SARS but serologically proven to be negative for SARS and in 197 serum samples from healthy donors and non-SARS febrile patients. The specificity of the assay was 100%. Furthermore, of 16 sera collected from four patients during the SARS recurrence in Guangzhou, 5 sera collected from 7 to 9 days after the onset of symptoms were positive for the N protein. N protein detection exhibited a high positive rate, 96 to 100%, between day 3 and day 5 after the onset of symptoms for 27 neutralization test-positive SARS patients and 298 serologically confirmed patients. The N protein detection rate continually decreased beginning with day 10, and N protein was not detected beyond day 19 after the onset of symptoms. In conclusion, an antigen capture ELISA reveals a high N protein detection rate in acute-phase sera of patients with SARS, which makes it useful for early diagnosis of SARS.


title: Type of Multimorbidity and Propensity to Seek Care among Elderly Medicare.

text: Greater propensity to seek care is critical for improving health of elderly individuals with multimorbidity. We used the Medicare Current Beneficiary Survey (2012) to assess propensity to seek care among community-dwelling elderly Medicare beneficiaries (≥ 65 yrs.; N=11,270) having (1) no physical or mental illness; (2) single physical or mental condition; (3) multimorbidity with physical conditions only; and (4) multimorbidity with both physical and mental conditions. As compared to multimorbidity with physical conditions, elderly with no multimorbidity were less likely (Adjusted Odds Ratio [95% CI]: 0.50 [0.36, 0.68]) and elderly with both physical and mental conditions were more likely (1.57 [1.28, 1.93]) to have a health problem for which they should have seen a doctor but did not. Further, elderly having a usual source of care were less likely (0.53 [0.37, 0.75]) to have a health problem for which they should have seen a doctor but did not. Multimorbidity is negatively associated with propensity to seek care. The presence of both chronic mental and physical conditions worsened propensity to seek care among elderly individuals. Future efforts to increase the awareness of receiving timely care and improve the access to care can enhance propensity to seek care among elderly individuals with multimorbidity.


title: Protecting against SARS during equipment maintenance.

text: The recent outbreak of severe acute respiratory syndrome (SARS) raises questions about the appropriate infection control measures to use when conducting maintenance procedures on medical devices that may have been exposed to the SARS virus--that is, devices that have been used on, or located in the same room as, a patient with (or suspected to have) SARS. Although there is considerable information and guidance available on many aspects of SARS, very little exists on this particular topic. What's more, we have found significant differences in the perspectives and recommendations of some of the experts on the subject. This article provides guidance for clinical engineering, respiratory therapy, and other personnel involved in maintaining potentially SARS-exposed equipment. To derive our recommendations, we reviewed the material posted on the Web sites of the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), along with other information sources; we also discussed issues related to equipment use and servicing with experts outside ECRI.


title: What is the evidence that bovine coronavirus is a biologically significant respiratory pathogen in cattle?

text: Coronaviruses, including bovine coronavirus (BCoV), are etiologically associated with enteric and respiratory disease across a wide range of mammalian and avian species. The role of BCoV in calfhood diarrhea is well-established, but its role in the bovine respiratory disease complex (BRDC) has been controversial. This review re-examines the evidence that BCoV is a significant pathogen in the BRDC.


title: Spatial dynamics of an epidemic of severe acute respiratory syndrome in an urban area.

text: OBJECTIVE To map risk of exposure to severe acute respiratory syndrome (SARS) in an urban area and assess the ability of traditional interventions to control dispersion of the disease. METHODS Data on the Beijing SARS epidemic were used to map spatial clusters of identified contacts and to estimate transmission of SARS using a model with a time-dependent transmission rate. RESULTS The estimated transmission rate decreased dramatically from 20 to 30 April 2003. The total number of cases in the epidemic in Beijing was estimated to be 2521. Hierarchical clustering revealed that risk-exposures were widespread, but clustered in a pattern that is distinctly related to the Beijing urban ring roads. CONCLUSION Traditional control measures can be very effective at reducing transmission of SARS. Spatial patterns of risk-exposures can inform disease surveillance, prediction and control by identifying spatial target areas on which interventions should be focused.


Cuts to the NHMRC budget will undermine the health of all Australians - today and in the future.


title: Replacing Paper Informed Consent with Electronic Informed Consent for Research in Academic Medical Centers: A Scoping Review.

text: Although experts have identified benefits to replacing paper with electronic consent (eConsent) for research, a comprehensive understanding of strategies to overcome barriers to adoption is unknown. To address this gap, we performed a scoping review of the literature describing eConsent in academic medical centers. Of 69 studies that met inclusion criteria, 81% (n=56) addressed ethical, legal, and social issues; 67% (n=46) described user interface/user experience considerations; 39% (n=27) compared electronic versus paper approaches; 33% (n=23) discussed approaches to enterprise scalability; and 25% (n=17) described changes to consent elections. Findings indicate a lack of a leading commercial eConsent vendor, as articles described a myriad of homegrown systems and extensions of vendor EHR patient portals. Opportunities appear to exist for researchers and commercial software vendors to develop eConsent approaches that address the five critical areas identified in this review.


Tropical travel and life-threatening disease: preventing malaria misadventures.


title: [Initial analysis of complete genome sequences of SARS coronavirus].

text: Multiple sequence alignment among 12 complete SARS coronavirus (SARS-CoV) sequences reveals that the major parts of 29708 b of the genomes have 99.82% identical bases. Forty two nucleotide mismatches were found in addition to the five and six gaps in two genomes. Among them, 28 mismatches result in changes of amino acid in the encoded proteins. Analysis of the changes implies possible effect on the Spike and Membrane protein of the virus, while most of the other changes seem not very significant to alter the structure and function of the proteins. These results have been released on the anti-sars web site maintained by the Centre of Bioinformatics, Peking University (antisars.cbi.pku.edu.cn) and may be of help for further experimental study.


title: An established feline monocytic cell line.

text: A feline monocytic cell line was established from a venous blood sample obtained from a healthy male donor cat. The cloned cells, temporarily named FLMo/K02, were successively passaged in vitro with cell growth medium consisting of RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum. Non-specific esterase and acid phosphatase, as marker enzymes, were clearly demonstrated by cytochemical examinations. The cells treated with allogeneic serum for two hours in advance showed enhanced reactivity to monoclonal antibodies, feline CD1a, canine CD11b, feline CD11c, canine CD11d, and feline MHC-II.


Emergence of novel coronavirus: global context.


Network medicine--from obesity to the "diseasome".


title: trans regulation of cap-independent translation by a viral subgenomic RNA.

text: Many positive-strand RNA viruses generate 3'-coterminal subgenomic mRNAs to allow translation of 5'-distal open reading frames. It is unclear how viral genomic and subgenomic mRNAs compete with each other for the cellular translation machinery. Translation of the uncapped Barley yellow dwarf virus genomic RNA (gRNA) and subgenomic RNA1 (sgRNA1) is driven by the powerful cap-independent translation element (BTE) in their 3' untranslated regions (UTRs). The BTE forms a kissing stem-loop interaction with the 5' UTR to mediate translation initiation at the 5' end. Here, using reporter mRNAs that mimic gRNA and sgRNA1, we show that the abundant sgRNA2 inhibits translation of gRNA, but not sgRNA1, in vitro and in vivo. This trans inhibition requires the functional BTE in the 5' UTR of sgRNA2, but no translation of sgRNA2 itself is detectable. The efficiency of translation of the viral mRNAs in the presence of sgRNA2 is determined by proximity to the mRNA 5' end of the stem-loop that kisses the 3' BTE. Thus, the gRNA and sgRNA1 have "tuned" their expression efficiencies via the site in the 5' UTR to which the 3' BTE base pairs. We conclude that sgRNA2 is a riboregulator that switches off translation of replication genes from gRNA while permitting translation of structural genes from sgRNA1. These results reveal (i) a new level of control of subgenomic-RNA gene expression, (ii) a new role for a viral subgenomic RNA, and (iii) a new mechanism for RNA-mediated regulation of translation.


Personal protective equipment for preventing respiratory infections: what have we really learned?


title: Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Thus, vaccination against SARS-CoV may represent an effective approach towards controlling SARS. The nucleocapsid (N) protein is thought to play a role in induction of cell-mediated immunity to SARS-CoV and thus it is important to characterize this protein. In the present study, an E1/partially E3-deleted, replication-defective human adenovirus 5 (Ad5) vector (Ad5-N-V) expressing the SARS-CoV N protein was constructed. The N protein, expressed in vitro by Ad5-N-V, was of the expected molecular mass of 50 kDa and was phosphorylated. Vaccination of C57BL/6 mice with Ad5-N-V generated potent SARS-CoV-specific humoral and T cell-mediated immune responses. These results show that Ad5-N-V may potentially be used as a SARS-CoV vaccine.


Identification and control are the priority.


title: Fusion formation by the uncleaved spike protein of murine coronavirus JHMV variant cl-2.

text: The fusogenic properties of the uncleaved spike (S) protein of murine coronavirus JHMV variant cl-2 were studied by expressing the S protein with a deleted putative cleavage site. The amino acid sequence of the putative cleavage site, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala-Leu-Glu by in vitro mutagenesis of the cl-2 S protein cDNA. Recombinant vaccinia viruses containing the cl-2 S cDNA [RVV t(+)] or the mutated cDNA [RVV t(-)] were constructed and monitored for fusion formation and cleavage of the expressed S proteins. When cultured DBT cells were infected with RVV t(+) at a multiplicity of infection of 0.5, fusion formation was first observed at 10 to 12 h postinoculation and spread throughout the whole culture by 20 to 24 h postinoculation. In cells infected with RVV t(-) under the same conditions, fusion formation appeared by 12 to 14 h. This result represented a 2- to 4-h delay in the onset of fusion, compared with its appearance in cells expressing the wild-type S protein. By 25 to 30 h, most of the cells infected by RVV t(-) had fused. By immunoprecipitation and Western blotting (immunoblotting), the 170-kDa S protein was detected in DBT cells expressing the wild-type S protein and the mutated S protein. However, interestingly, the cleavage products of the S protein, S1 and S2, were not detected in RVV t(-)-infected cells, producing the mutated S protein, even though fusion was clearly visible. Both products were, of course, detected in RVV t(+)-infected DBT cells, producing the wild-type S protein. The same results concerning the fusion formation and cleavage properties of the S proteins were reproduced by the transiently expressed S proteins. These results suggest that the cleavage event in the S protein of murine coronavirus JHMV is not a prerequisite for fusion formation but that it does facilitate fusion formation.


Oral antihistamine/decongestant/analgesic combinations for the common cold.


title: Unusual heterogeneity of leader-mRNA fusion in a murine coronavirus: implications for the mechanism of RNA transcription and recombination.

text: Coronavirus mRNA transcription was thought to be regulated by the interaction between the leader RNA and the intergenic sequence (IS), probably involving direct RNA-RNA interactions between complementary sequences. In this study, we found that a particular strain of mouse hepatitis virus, JHM2c, which has a deletion of a 9-nucleotide (nt) sequence (UUUAUAAAC) immediately downstream of the leader RNA, transcribed subgenomic mRNA species containing a whole array of heterogeneous leader fusion sites. Using a transfected defective interfering RNA which contains an IS and a reporter (chloramphenicol acetyltransferase) gene and JHM2c as a helper virus, we demonstrated that subgenomic mRNAs transcribed from the defective interfering RNAs were extremely heterogeneous. The leader-mRNA fusion sites in this virus can be grouped into five types. In type I, the leader is fused with the consensus IS of the template RNA at a site within the UCUAA repeats, consistent with the classical model of discontinuous transcription. In type II, the leader is fused with the consensus IS as in type I, but the leader of mRNA contains some nucleotide substitutions within the UCUAA repeats. In type III, the leader is fused with mRNAs at a site either upstream or downstream of the consensus IS. The sequences around the fusion sites bear little or no homology to the leader. As a result, mRNAs contain sequences complementary to the template sequences upstream of the IS or have sequence deletions downstream of the IS. In type IV, the leader is fused to the IS at the 9-nt sequence immediately downstream of the UCUAA repeats. In type V, the leader-mRNA fusion site contains a duplication of a portion of the leader sequence or an insertion of nontemplated sequences which are not present in either leader or template RNA. These patterns of leader-mRNA fusion resemble the aberrant homologous recombination frequently seen in other RNA viruses. The degree of heterogeneity of leader fusion sites is dependent on the sequences of both the leader RNA and IS. These results suggest that leader-mRNA fusion in coronavirus transcription does not require direct RNA-RNA interaction between complementary sequences. A modified model of RNA transcription and recombination based on protein-RNA and protein-protein interactions is proposed. This study also provides a paradigm for aberrant homologous recombination.


title: A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.

text: Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves were administered sucrose and diuretic agents for 48 h to induce diarrhea and severe dehydration. Clinical changes after 48 h were severe watery diarrhea, severe depression, and marked dehydration (mean, 14% BW loss). Cardiac output, stroke volume, mean central venous pressure, plasma volume, thiocyanate space, blood pH and bicarbonate concentration, base excess, serum chloride concentration, and fetlock temperature were decreased. Plasma lactate concentration, hematocrit, and serum potassium, creatinine, phosphorus, total protein and albumin concentrations were increased. This non-infectious calf diarrhea protocol has a 100% response rate, while providing a consistent and predictable hypovolemic state with diarrhea that reflects most of the clinicopathologic changes observed in osmotic/maldigestive diarrhea caused by infection with rotavirus, coronavirus or cryptosporidia. Limitations of the protocol, when compared to infectious diarrhea models, include failure to induce a severe metabolic acidosis, absence of hyponatremia, renal instead of enteric loss of chloride, renal as well as enteric loss of free water, absence of profound clinical depression and suspected differences in the morphologic and functional effect on intestinal epithelium. Despite these differences, the sucrose/diuretic protocol should be useful in the initial screening of new treatment modalities for calf diarrhea. To confirm their efficacy, the most effective treatment methods should then be examined in calves with naturally-acquired diarrhea.


title: Coronaviruses in bent-winged bats (Miniopterus spp.).

text: A novel group 1 coronavirus was previously identified in bent-winged bats (Miniopterus spp.). Here, results are described from our ongoing surveillance of these bats for coronaviruses. These findings show that group 1 coronaviruses are endemic in these bat populations in Hong Kong. Genetic analysis of these viruses indicates that there are at least four different, but closely related, group 1 coronaviruses (bat-CoV 1A, 1B, HKU7 and HKU8) circulating in bent-winged bats. Phylogenetic analysis revealed that these group 1 bat coronaviruses have descended from a common ancestor and that these viruses have been established in these bats for a long period of time. These data provide a better understanding of the emergence and evolution of coronaviruses. Bat-CoV 1A and 1B were detected in apparently healthy Miniopterus magnater and Miniopterus pusillus, respectively, on repeated sampling occasions at a single habitat, suggesting that these viruses have established a persistent infection in these populations.


title: Right upper lobe collapse secondary to an anomalous bronchus after endotracheal intubation for routine surgery.

text: Perioperative hypoxaemia is a common but serious problem with well recognised causes. However, an anomalous bronchus causing lobar collapse as a cause is seldom mentioned. A healthy young male patient was anaesthetised for a knee operation. He required re-intubation immediately postoperatively for hypoxia. He was found to have right upper lobe collapse. Fibreoptic examination of the trachea demonstrated an anomalous bronchus as the cause. Intra-operatively, the endotracheal tube had been inserted too deeply and the bronchial orifice had been obstructed by the tip. It took several hours for the lung to re-expand. Greater awareness of this potential complication is needed.


title: Review of retention strategies in longitudinal studies and application to follow-up of ICU survivors.

text: OBJECTIVE To review the literature on retention strategies in follow-up studies and their relevance to critical care and to comment on the Toronto experience with the acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome (SARS) follow-up studies. DESIGN AND SETTING Literature review and two cohort studies in a tertiary care hospital in Toronto, Canada. PATIENTS AND PARTICIPANTS ARDS and SARS patients. MEASUREMENTS AND RESULTS Review articles from the social sciences and medicine are summarized and our own experience with two longitudinal studies is drawn upon to elucidate strategies that can be successfully used to attenuate participant drop-out from longitudinal studies. Three key areas for retention of subjects are identified from the literature: (a) respect for patients: respect for their ideas and their time commitment to the research project; (b) tracking: collect information on many patient contacts at the initiation of the study and outline tracking procedures for subjects lost to follow-up; and (c) study personnel: interpersonal skills must be reinforced, flexible working hours mandated, and support offered. Our 5-year ARDS and 1-year SARS study retention rates were 86% and 91%, respectively, using these methods. CONCLUSIONS Strategies to reduce patient attrition are time consuming but necessary to preserve internal and external validity. When the follow-up system is working effectively, researchers can acquire the necessary data to advance knowledge in their field and patients are satisfied that they have an important role to play in the research project.


title: Measurement of intra-abdominal pressure in large incisional hernia repair to prevent abdominal compartmental syndrome.

text: INTRODUCTION The repair of large incisional hernias may occasionally lead to a substantial increase in intra-abdominal pressure (IAP), and rarely to abdominal compartmental syndrome (ACS) with subsequent respiratory, vascular, and visceral complications. Measurement of the IAP has recently become a common practice in monitoring critical patients, even though such measurements were obtained in the early 1900s. PATIENTS AND METHODS A prospective study involving 54 patients undergoing elective abdominal wall gap repair (mean length, 17.4 cm) with a tension-free technique after incisional hernia was conducted. The purpose of the study was to determine whether or not urinary pressure for indirect IAP measurement is a reliable method for the early identification of patients with a higher risk of developing ACS. IAP measurements were performed using a Foley catheter connected to a HOLTECH® medical manometer. IAP values were determined preoperatively, after anesthetic induction, upon patient awakening, upon patient arrival in the ward after surgery, and 24 h after surgery before removing the catheter. All patients were treated by the same surgical team using a prosthetic composite mesh (PARIETEX®). RESULTS Incisional hernia repair caused an increase in the mean IAP score of 2.68 mmHg in 47 of 54 patients (87.04%); the IAP was decreased in two patients (3.7%) and remained equal in five patients before and 24 h after surgery (9.26%). FEV-1, measured 24 h after surgery, increased in 50 patients (92.6%), remained stable in two patients (3.7%), and decreased in two patients (3.7%). The mean increase in FEV-1 was 0.0676 L (maximum increase = 0.42 L and minimum increase = 0.01 L) in any patient who developed ACS. CONCLUSIONS Measurement of urinary bladder pressure has been shown to be easy to perform and free of complications. Measurement of urinary bladder pressure can also be a useful tool to identify patients with a higher risk of developing ACS.


title: Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state.

text: The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.


title: Balloon-assisted coiling of the cavernous sinus to treat direct carotid cavernous fistula. A single center experience of 13 consecutive patients.

text: This study evaluated clinical and neuroradiological results in 13 consecutive patients with spontaneous and traumatic direct carotid cavernous fistulas treated at our center between January 2006 and September 2012. All patients were treated by coiling of the cavernous sinus. Coiling was always performed while a semi-compliant non-detachable balloon was temporarily inflated in the internal carotid artery. This technique (balloon-assisted coiling) permitted a clear visualization of the fistula, facilitated coil positioning and protected the patency of the artery. All patients' clinical data and radiological examinations were reviewed; nine patients underwent radiological and clinical follow-up, with a mean duration of 3.8 years (range: six months-six years). Overall results at discharge showed a complete occlusion of the fistula in seven patients (7/13, 54%) and a resolution of symptoms in eight patients (8/12, 67%). Radiological follow-up showed complete occlusion of the fistula in all patients (9/9, 100%) and clinical follow-up showed a resolution of symptoms in eight patients (8/9, 89%) and persistent symptoms in one (1/9, 11%). No procedure-related complications occurred. Balloon-assisted coiling of the cavernous sinus for the treatment of direct carotid cavernous fistulas proved an effective and safe technique, both in angiographic and clinical terms, and may be considered a technical improvement.


Fear, Preparedness and Covid-19.


title: Severe acute respiratory syndrome: another challenge for critical care nurses.

text: Severe acute respiratory syndrome (SARS) is a viral disease that may be contracted by exposure to a newly recognized form of the coronavirus. It often manifests through a set of common respiratory symptoms that include fever and nonproductive cough. To date, SARS has no vaccine or definitive treatment. Approximately 20% of SARS patients develop respiratory failure, which requires mechanical ventilation and close cardiopulmonary monitoring. Intensive care unit (ICU) nurses and other healthcare workers who care for SARS patients are at risk of contracting the disease. Thus, it is important that ICU nurses be familiar with the disease and its implications for critical care. This article provides critical care nurses with an update on the first SARS outbreak, its origin, case definition, clinical manifestations, diagnosis, relevant infection control practices, management, and recommendations for the role of ICU nurses in dealing with future outbreaks.


title: Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecal Escherichia coli.

text: Fifty-two newborn Holstein calves with serum IgG concentrations less than 0.73 g.dL(-1) were randomly assigned to one of four treatments: no added live yeast (control), 0.5 g of live yeast added to the grain for 84 d (SC; Saccharomyces cerevisiae), 0.5 g of live yeast added to the milk for 42 d (SB; S. cerevisiae, spp. boulardii), and 0.5 g of live yeast added to the grain for 84 d and to the milk for 42 d (SCSB). Calves were offered 440 g of milk replacer DM for the first 42 d and grain for ad libitum intake throughout the study. Plasma was analyzed weekly for concentrations of glucose and beta-hydroxybutyrate. Escherichia coli isolated from fecal samples collected every 2 weeks were used for determination of antibiotic resistance patterns. Calves receiving SC consumed more grain DM, had increased weight gain prior to weaning, and increased plasma glucose concentrations compared to controls. Days with diarrhea were reduced by feeding live yeast to calves. Antibiotic resistance in fecal E. coli was associated with the age of calves with highest levels of resistance observed in the 3 d calves. While calves receiving SCSB had higher levels of antibiotic resistance than controls, this effect was not associated with any of the other treatments. Improvements in performance of calves with failure of passive transfer were observed when live yeast was added only to the grain.