title: Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway.

text: BACKGROUND Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. METHODS We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. RESULTS A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following well-established guidelines for adopting the technology. Preliminary data demonstrate that perioperative convalescence may exceed end points when compared with the open technique. CONCLUSIONS The robotic Whipple procedure is a minimally invasive approach for select patients as part of multidisciplinary management of periampullary lesions in tertiary centers where clinicians have developed robotic surgical programs. Prospective trials are needed to define the short- and long-term benefits of the robotic Whipple procedure.


Morphology of a latent virus associated with hamster cells BHK-21.


title: Performance of ICU ventilators during noninvasive ventilation with large leaks in a total face mask: a bench study.

text: OBJECTIVE Discomfort and noncompliance with noninvasive ventilation (NIV) interfaces are obstacles to NIV success. Total face masks (TFMs) are considered to be a very comfortable NIV interface. However, due to their large internal volume and consequent increased CO2 rebreathing, their orifices allow proximal leaks to enhance CO2 elimination. The ventilators used in the ICU might not adequately compensate for such leakage. In this study, we attempted to determine whether ICU ventilators in NIV mode are suitable for use with a leaky TFM. METHODS This was a bench study carried out in a university research laboratory. Eight ICU ventilators equipped with NIV mode and one NIV ventilator were connected to a TFM with major leaks. All were tested at two positive end-expiratory pressure (PEEP) levels and three pressure support levels. The variables analyzed were ventilation trigger, cycling off, total leak, and pressurization. RESULTS Of the eight ICU ventilators tested, four did not work (autotriggering or inappropriate turning off due to misdetection of disconnection); three worked with some problems (low PEEP or high cycling delay); and one worked properly. CONCLUSIONS The majority of the ICU ventilators tested were not suitable for NIV with a leaky TFM.


Is the Quarantine Act relevant?


title: [Development of Novel Multiplex Real-time RT-PCR Assays for Detection of MERS-CoV Infection].

text: We aimed to develop a novel laboratory assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) infection .Several novel multiplex real-time RT-PCR assays were developed using the upE,ORF1 band N2genes of MERS-CoV as targets; the novel assays were compared with previous monoplex real-time RT-PCR assays. For validation, we tested a MERS-CoV strain (hCoVEMC), clinical specimens from patients with fever in Shanghai, and specimens from the first imported MERS case in China. The detection limit of the novel multiplex real-time RT-PCR assays was 10 PFU of MERS-CoV per ml, the same as that in monoplex real-time RT-PCR assays based on upE or N2. The detection was specific for MERS-CoV. In validation using clinical samples, pharyngeal swabs from Shanghai patients were detected as negative, while swabs from the first imported MERS case in China were detected as positive. Using whole blood samples from a MERS case, better detection results were obtained with N2 as the target than upE. We conclude that all the novel assays established in this study could be used for the detection of MERS-CoV; they show potential for improvement compared with monoplex real-time RT-PCR assay based on upE.


title: Pathology of guinea pigs experimentally infected with a novel reovirus and coronavirus isolated from SARS patients.

text: Guinea pigs were inoculated with a reovirus (ReoV) and coronavirus (SARS-CoV) isolated from SARS patients to determine their potential role in the etiology of SARS. Animals infected with ReoV died between day 22 and day 30 postinoculation (PI) while 70% of the animals inoculated with ReoV and SARS-CoV died between day 4 to day 7 PI. The titer of neutralizing antibodies against ReoV and SARS-CoV ranged from 80 to 160 when the animals were inoculated with the two viruses, respectively, while the titer of the antibodies was just below 10 in coinfections. The animal inoculated with ReoV developed diffuse alveolar damage similar to the exudative and leakage inflammation found in SARS patients, and was characterized by diffuse hemorrhage, fibroid exudation, hyaline membrane formation, and type II pneumocytes hyperplasia in alveolar interstitia. The pulmonary epithelial necrosis, excoriation, and early fibrosis of pulmonary tissue were only observed in ReoV-SARS-CoV groups and in SARS-CoV/ReoV groups. Other typical pathological changes included hemorrhagic necrosis in lymph nodes and spleen and hydropic degeneration in the liver. On the contrary, guinea pigs infected with SARS-CoV only developed interstitial pneumonitis. Our experiment demonstrate that ReoV might be one of the primary causes of SARS, since simultaneous coinfection can duplicate the typical pathological changes similar to that of SARS patients. This guinea pig model may provide a useful animal model for SARS.


title: Novel Coronavirus Disease (COVID-19) and Central Nervous System Complications: What Neurologist Need to Know.

text: The novel coronavirus (Covid-19) is a family of large enveloped non-segmented positive-sense RNA viruses which has been considered as a global health concern as it has a very high transmissibility potential. Regarding to the similarity of the virus to SARS-CoV, it is postulated that the Covid-19 accumulates mainly in the nasal epithelia and lower respiratory airways. However, there is evidence suggesting the Covid-19 neurotropism which might contribute to respiratory failure. Here in we aim to review the central nervous system complications of the Covid-19 CoV since the emergence of the virus. Keywords: Novel Coronavirus, Covid19-Cov, CNS Complication, Nervous System.


title: 5-millimeter trocar-site bowel herniation following laparoscopic surgery.

text: BACKGROUND AND OBJECTIVES This is a case report of a 5-mm trocar-site large bowel herniation following laparoscopic tubal sterilization. During laparoscopic sterilization, the 5-mm port site was closed initially. Large bowel herniation was recognized at the end of the case and managed immediately by laparoscopically reducing the hernia and closing the port site without any short- or long-term complications. Trocar-site bowel hernia is a rare complication after laparoscopic surgery. It is usually associated with trocar size > 10 mm. We describe a case of bowel herniation through a 5-mm trocar site, which was managed after laparoscopic surgery. CASE REPORT A 36-year-old multigravid patient underwent a laparoscopic tubal fulguration. Two 5-mm ports were used for the procedure. At the end of the procedure, the lateral trocar site was found to have fat protrusion that looked like appendices epiploicae. A laparoscopic camera was reintroduced into the abdominal cavity that showed a large bowel herniation through the 5-mm lateral port site. The hernia was reduced laparoscopically, and the fascial defect was repaired. CONCLUSION Bowel herniation can occur through a 5-mm port. All port sites should be closed to avoid such complications.


title: A human rights approach to the WHO Model List of Essential Medicines.

text: Since the first WHO Model List of Essential Medicines was adopted in 1977, it has become a popular tool among health professionals and Member States. WHO's joint effort with the United Nations Committee on Economic, Social and Cultural Rights has resulted in the inclusion of access to essential medicines in the core content of the right to health. The Committee states that the right to health contains a series of elements, such as availability, accessibility, acceptability and quality of health goods, services and programmes, which are in line with the WHO statement that essential medicines are intended to be available within the context of health systems in adequate amounts at all times, in the appropriate dosage forms, with assured quality and information, and at a price that the individual and the community can afford. The author considers another perspective by looking at the obligations to respect, protect and fulfil the right to health undertaken by the states adhering to the International Covenant of Economic, Social and Cultural Rights (ICESCR) and explores the relationship between access to medicines, the protection of intellectual property, and human rights.


title: Downregulation of autophagy by herpesvirus Bcl-2 homologs.

text: The critical role of the cellular autophagy pathway in viral infection and pathogenesis has become increasingly apparent. Mounting evidences suggest that viruses have developed different strategies to meticulously modulate intracellular autophagy for their own benefits, thereby either promoting efficient viral replication or facilitating viral persistence. While our understanding of these strategies is still in its incipient stage, recent advances demonstrate that gamma herpesvirus Bcl-2 homolog (vBcl-2), which protects virus-infected cells from apoptosis, also suppresses cellular autophagy pathway through its direct interaction with the autophagy protein Beclin1. Interestingly, vBcl-2 has evolved to harbor the enhanced anti-autophagic activity compared to its host counterpart, suggesting an important role of cellular autophagy in response to viral infection and virus-associated pathogenesis. Thus, a detailed study of vBcl-2-mediated regulation of autophagy signal transduction pathway may lead to a better understanding of not only how virus escapes from host innate immunity but also how autophagy regulates viral infection and environmental stresses.


title: Day-night differences in mucosal plasma proteins in common cold.

text: Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.


title: Effect of intranasal vaccination against bovine enteric coronavirus on the occurrence of respiratory tract disease in a commercial backgrounding feedlot.

text: OBJECTIVE To measure antibody titers against bovine coronavirus (BCV), determine frequency of BCV in nasal swab specimens, and compare calves treated for bovine respiratory tract disease (BRD) between those given an intranasally administered vaccine and control calves. DESIGN Randomized clinical trial. ANIMALS 414 heifer calves. PROCEDURE Intranasal BCV antigen concentration and antibody titer against BCV were measured on entry to a feedlot. Calves were randomly assigned to receive 3.0 mL of a modified-live virus vaccine against bovine enteric coronavirus and rotavirus or 3.0 mL of saline (0.9% NaCl) solution. Calves were confined to 1 of 2 pens, depending on vaccination status, for a minimum of 17 days of observation (range, 17 to 99). Selection of calves for treatment of BRD and scoring for severity of disease were done by veterinarians unaware of treatment status. RESULTS Intranasal BCV (125/407 [31%]) and serum antibody titers > or = 20 against BCV (246/396 [62%]) were identified in calves entering the feedlot. Vaccination was associated with significant decrease in risk of treatment for BRD; intranasal BCV on entry to the feedlot was associated with increased risk of treatment. Univariate analysis revealed that control calves with intranasal BRD on entry to the feedlot and those with antibody titer < 20 were significantly more likely to be treated for BRD. CONCLUSIONS AND CLINICAL RELEVANCE These data provide further evidence of an association between BCV and respiratory tract disease in feedlot calves. An intranasally administered vaccine appeared to reduce risk of treatment for BRD.


title: Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential.

text: Resveratrol, a polyphenol found in numerous plant species, including mulberries, peanuts and grapes, has shown to possess chemopreventive properties against several cancers, and cardiovascular diseases. Recently, resveratrol has been shown to have positive effects on age longevity, lipid levels and a preventative quality against certain cancers and viral infections. Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53, TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity. Modulation of cell signaling pathway by resveratrol explains its diverse bioactivities related with human health. Resveratrol also potentiates the apoptotic effects of cytokines, chemotherapeutic agents and gamma-radiation. Pharmacokinetic and pharmacodynamic studies demonstrated that the main target organs of resveratrol are liver and kidney, and it is metabolized by hydroxylation, glucuronidation, sulfation and hydrogenation. As a chemoprevention agent, resveratrol has been shown to inhibit tumor initiation, promotion, and progression. There is growing evidence that resveratrol can prevent or delay the onset of various cancers, heart diseases, ischemic and chemically induced injuries, pathological inflammation and viral infections. This review summarizes the molecular mechanisms of resveratrol and its clinical benefits for human diseases.


Fact sheet on Middle East respiratory syndrome coronavirus (June 2015).


docid: nbuhyfxb

title: Evaluation of concurrent shedding of bovine coronavirus via the respiratory tract and enteric route in feedlot cattle.

text: OBJECTIVE To assess the relationship between shedding of bovine coronavirus (BCV) via the respiratory tract and enteric routes and the association with weight gain in feedlot cattle. ANIMALS 56 crossbred steers. PROCEDURES Paired fecal samples and nasal swab specimens were obtained and were tested for BCV, using antigen-capture ELISA. Paired serum samples obtained were tested for antibodies to BCV, using antibody-detection ELISA. Information was collected on weight gain, clinical signs, and treatments for enteric and respiratory tract disease during the study period. RESULTS Number of samples positive for bovine respiratory coronavirus (BRCV) or bovine enteric coro navirus (BECV) was 37/224 (17%) and 48/223 (22%), respectively. Some cattle (25/46, 45%) shed BECV and BRCV. There were 25/29 (86%) cattle positive for BECV that shed BRCV, but only 1/27 (4%) cattle negative to BECV shed BRCV. Twenty-seven of 48 (56%) paired nasal swab specimens and fecal samples positive for BECV were positive for BRCV. In contrast, only 10/175 (6%) paired nasal swab specimens and fecal samples negative for BECV were positive for BRCV. Only shedding of BECV was associated with significantly reduced weight gain. Seroconversion to BCV during the 21 days after arrival was detected in 95% of the cattle tested. CONCLUSIONS AND CLINICAL IMPLICATIONS Feedlot cattle infected with BCV after transport shed BCV from the respiratory tract and in the feces. Fecal shedding of BCV was associated with significantly reduced weight gain. Developing appropriate control measures for BCV infections could help reduce the decreased weight gain observed among infected feedlot cattle.


title: Natural history of a recurrent feline coronavirus infection and the role of cellular immunity in survival and disease.

text: We describe the natural history, viral dynamics, and immunobiology of feline infectious peritonitis (FIP), a highly lethal coronavirus infection. A severe recurrent infection developed, typified by viral persistence and acute lymphopenia, with waves of enhanced viral replication coinciding with fever, weight loss, and depletion of CD4+ and CD8+ T cells. Our combined observations suggest a model for FIP pathogenesis in which virus-induced T-cell depletion and the antiviral T-cell response are opposing forces and in which the efficacy of early T-cell responses critically determines the outcome of the infection. Rising amounts of viral RNA in the blood, consistently seen in animals with end-stage FIP, indicate that progression to fatal disease is the direct consequence of a loss of immune control, resulting in unchecked viral replication. The pathogenic phenomena described here likely bear relevance to other severe coronavirus infections, in particular severe acute respiratory syndrome, for which multiphasic disease progression and acute T-cell lymphopenia have also been reported. Experimental FIP presents a relevant, safe, and well-defined model to study coronavirus-mediated immunosuppression and should provide an attractive and convenient system for in vivo testing of anticoronaviral drugs.


docid: jugpviip

title: [Recommendations for resource management in intensive care units during the COVID-19 pandemic].

text: This document aims to provide evidence-based recommendations to estimate the personal protective equipments (PPE), medical devices, and drugs commonly used in the Intensive Care Unit during the COVID-19 pandemic. A systematic literature review and gray literature assessment was performed, and the evidence was categorized using the GRADE methodology. Then a predictive model was built to support the estimation of resources needed during 30 days of the pandemic. In the development of these recommendations, 33 publications were included, with variable quality of evidence (low to very low quality). They refer to the use of PPE according to the risk of exposure; management and reuse of PPE, and the stock of drugs and medical devices needed for the care of patients with COVID-19. It is important to remark the difficult in estimating and managing the number of essential supplies and equipment required during a pandemic. The model allowed us to predict the resources required to provide critical care during 30 days of pandemic activity. Given the constant evolution of COVID-19, these recommendations might change as evidence evolves.


title: Endovascular management of internal carotid artery injuries secondary to endonasal surgery: case series and review of the literature.

text: OBJECTIVE Internal carotid artery (ICA) injury is a rare but severe complication of endonasal surgery. The authors describe their endovascular experience managing ICA injuries after transsphenoidal surgery; they review and summarize the current literature regarding endovascular techniques; and they propose a treatment algorithm based on the available evidence. METHODS A retrospective review of 576 transsphenoidal pituitary adenoma resections was performed. Cases of ICA injury occurring at our institution and transfers from other hospitals were evaluated. Endovascular treatments for ICA injury reported in the literature were also reviewed and summarized. RESULTS Seven cases were identified from the institutional cohort (mean age 46.3 years, mean follow-up 43.4 months [1-107 months]) that received endovascular treatment for ICA injury. Five injuries occurred at our institution (5 [0.9%] of 576), and 2 injuries occurred at outside hospitals. Three patients underwent ICA sacrifice by coil placement, 2 underwent lesion embolization (coil or stent-assisted coil placement), and 2 underwent endoluminal reconstruction (both with flow diversion devices). Review of the literature identified 98 cases of ICA injury treated with endovascular methods. Of the 105 total cases, 46 patients underwent ICA sacrifice, 28 underwent lesion embolization, and 31 underwent endoluminal reconstruction. Sacrifice of the ICA proved a durable solution in all cases; however, the rate of persistent neurological complications was relatively high (10 [21.7%] of 46). Lesion embolization was primarily performed by coil embolization without stenting (16 cases) and stent-assisted coiling (9 cases). Both techniques had a relatively high rate of at least some technical complication (6 [37.5%] of 16 and 5 [55.6%] of 9, respectively) and major technical complications (i.e., injury, new neurological deficit, or ICA sacrifice) (5 [31.3%] of 16 and 2 [22.2%] of 9, respectively). Endoluminal reconstruction was performed by covered stent (24 cases) and flow diverter (5 cases) placement. Covered stents showed a reasonably high rate of technical complications (10 [41.7%] of 24); however, 8 of these problems were resolved, leaving a small percentage with major technical complications (2 [8.3%] of 24). Flow diverter placement was also well tolerated, with only 1 minor technical complication. CONCLUSIONS Endovascular treatments including vessel sacrifice, coil embolization (with or without stent assistance), and endoluminal reconstruction offer a tailored approach to ICA injury management after endonasal surgery. Vessel sacrifice remains the definitive treatment for acute, uncontrolled bleeding; however, vessel preservation techniques should be considered carefully in select patients. Multiple factors including vascular anatomy, injury characteristics, and risk of dual antiplatelet therapy should guide best treatment, but more study is needed (particularly with flow diverters) to refine this decision-making process. Ideally, all endovascular treatment options should be available at institutions performing endonasal surgery.


title: [Optimum hepatic parenchymal dissection to prevent bile leak: a comparative study using electrosurgical and stapling devices in swine].

text: BACKGROUND Bile leakage is a serious complication of liver resection, and its treatment is very time-consuming. In open liver resection, Glisson's sheaths are usually disconnected by ligation to the extent possible during the parenchyma dissection. However, in laparoscopic surgery, the ligation, suture, and hemostasis are more difficult than in open surgery. For this reason, in laparoscopic liver resection, liver parenchyma dissection is generally accomplished using electrosurgical or stapling devices. PURPOSE The purpose of this study was to verify the authenticity of electrosurgical devices attached an automatic irrigation function (AI) and stapling devices for laparoscopic liver parenchymal dissection. METHODS Four devices were used for liver parenchymal dissection in laparoscopic hepatic wedge resection, in pigs: monopolar high-frequency electric cautery attached AI (MCI) (n = 6), bipolar high-frequency electric cautery attached AI (BCI) (n = 6), bipolar tissue sealing system (LigaSure) attached AI (BSI) and an endoscopic stapling device (ECHELON FLEX ENDOPATH) (ES). In each group, burst pressures were tested using an electronic manometer, paying special attention to the location (s) of the first disruption (s). The dissected tissues were examined histologically. RESULTS Pressures used in electrosurgical devices attach AI were significantly higher compared to pressures used in a ES (P < 0.001). While thermal denaturation of the liver parenchyma occurred at approximately 2-3 mm of depth when bipolar high-frequency electric cautery was used for dissection, it reached up to more than 10 mm with monopolar high-frequency electric cautery. All of the first disruption points of stapling were at stapling line. CONCLUSIONS Electrosurgical devices with an automatic irrigation function are useful devices to dissect the liver parenchyma.


title: The vaccinia virus 39-kDa protein forms a stable complex with the p4a/4a major core protein early in morphogenesis.

text: The vaccinia virus (VV) 39-kDa protein, the product of the A4L gene, is a highly antigenic protein of the viral core. Pulse-chase and immunoprecipitation experiments have shown that the 39-kDa protein interacts with p4a (encoded by the A10L gene), the precursor of the most abundant virion protein. This interaction is maintained with the processed 4a form that arises during virion maturation. The controlled disruption of mature viral particles showed that the 39-kDa and 4a proteins are tightly bound within the virion. Immunoelectron microscopy showed that both proteins first localize within the cytoplasm and later accumulate inside the viral factories, reaching these locations via a mechanism apparently unrelated to cellular membranes. Double labeling experiments showed a colocalization of both proteins in all virus-induced structures.


The Australian study of health and relationships: results for central Sydney, inner-eastern Sydney, and New South Wales.


title: Low prevalence of subclinical severe acute respiratory syndrome-associated coronavirus infection among hospital healthcare workers in Hong Kong.

text: We recruited 688 hospital healthcare workers who cared for patients with severe acute respiratory syndrome (SARS) and did not develop the disease in the Hong Kong outbreak in 2003. A questionnaire survey was conducted and serum samples were collected for SARS-associated coronavirus (SARS-CoV) antibody. The high-risk procedures performed and the types of unprotected exposures were recorded for analysis. Only 1 asymptomatic nurse had positive serological test. The result demonstrates the low rate of subclinical SARS-CoV infection in hospital healthcare workers and that the infection control practice against SARS in Hong Kong's hospitals during the outbreak was highly effective.


title: Localization of mouse hepatitis virus nonstructural proteins and RNA synthesis indicates a role for late endosomes in viral replication.

text: The aim of the present study was to define the site of replication of the coronavirus mouse hepatitis virus (MHV). Antibodies directed against several proteins derived from the gene 1 polyprotein, including the 3C-like protease (3CLpro), the putative polymerase (POL), helicase, and a recently described protein (p22) derived from the C terminus of the open reading frame 1a protein (CT1a), were used to probe MHV-infected cells by indirect immunofluorescence (IF) and electron microscopy (EM). At early times of infection, all of these proteins showed a distinct punctate labeling by IF. Antibodies to the nucleocapsid protein also displayed a punctate labeling that largely colocalized with the replicase proteins. When infected cells were metabolically labeled with 5-bromouridine 5'-triphosphate (BrUTP), the site of viral RNA synthesis was shown by IF to colocalize with CT1a and the 3CLpro. As shown by EM, CT1a localized to LAMP-1 positive late endosomes/lysosomes while POL accumulated predominantly in multilayered structures with the appearance of endocytic carrier vesicles. These latter structures were also labeled to some extent with both anti-CT1a and LAMP-1 antibodies and could be filled with fluid phase endocytic tracers. When EM was used to determine sites of BrUTP incorporation into viral RNA at early times of infection, the viral RNA localized to late endosomal membranes as well. These results demonstrate that MHV replication occurs on late endosomal membranes and that several nonstructural proteins derived from the gene 1 polyprotein may participate in the formation and function of the viral replication complexes.


Special report: highlights of the First Annual Scientific Meeting of the Canadian Orthopaedic Foot and Ankle Society, Winnipeg, Manitoba, October 4, 2003.


title: Three Eras in Global Tobacco Control: How Global Governance Processes Influenced Online Tobacco Control Networking.

text: Online networks can serve as a platform to diffuse policy innovations and enhance global health governance. This study focuses on how shifts in global health governance may influence related online networks. We compare social network metrics (average degree centrality [AVGD], density [D] and clustering coefficient [CC]) of Globalink, an online network of tobacco control advocates, across three eras in global tobacco control governance; pre-Framework Convention on Tobacco Control (FCTC) policy transfer (1992-1998), global regime formation through the FCTC negotiations (1999-2005), and philanthropic funding through the Bloomberg Initiative (2006-2012). Prior to 1999, Globalink was driven by a handful of high-income countries (AVGD=1.908 D=0.030, CC=0.215). The FCTC negotiations (1999-2005) corresponded with a rapid uptick in the number of countries represented within Globalink and new members were most often brought into the network through relationships with regional neighbors (AVGD=2.824, D=0.021, CC=0.253). Between 2006 and 2012, the centrality of the US in the network increases significantly (AVGD=3.414, D=0.023, CC=0.310). The findings suggest that global institutionalization through WHO, as with the FCTC, can lead to the rapid growth of decentralized online networks. Alternatively, private initiatives, such as the Bloomberg Initiative, can lead to clustering in which a single source of information gains increasing influence over an online network.


The time of cholera.


title: Synthesis of minus-strand copies of a viral transgene during viral infections of transgenic plants.

text: Viral transgenes designed to provide resistance to specific plant viruses frequently consist of the coat protein gene and a contiguous 3' untranslated region (3'UTR) of viral origin. In many RNA viruses the viral 3'UTR establishes a recognition and initiation site for viral RNA replication. Thus the transgenic transcript may contain a functional virus replication site. Experiments were designed to determine if a challenging virus would recognize this replication site on a nuclear derived transcript and synthesize the complementary RNA. These data demonstrate that upon infection by a virus that recognizes the viral replication site, a full-length complement of the transgenic transcript is produced. In these experiments the replication complex of Brome Mosaic bromovirus recognized the transgenic transcript derived from a Cowpea Chlorotic Mottle bromovirus transgene. The resulting RNA may contribute to RNA recombination events.


PreScription: COVID-19 and Compounding Pharmacists.


title: An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis.

text: The murine coronavirus neurotropic strain JHM (MHV-JHM) nucleocapsid (N) protein induces a strong T-helper cell response in Lewis rats. It has been shown previously that N-specific CD4+ T cells can confer protection against acute disease upon transfer to otherwise lethally infected rats. To define the major antigenic regions that elicit this T cell response, truncated fragments of N protein were expressed from a bacterial expression vector and employed as T cell antigens. Lymphocytes from either MHV-JHM-infected or immunized rats were stimulated in culture with virus antigen, grown and tested for their specificity to the N protein fragments. The carboxy-terminally located C4-N fragment (95 amino acids) induced the most pronounced proliferative response irrespective of whether the lymphocyte culture was derived from immunized or MHV-JHM-infected rats. We established T cell lines specific for the truncated N protein fragments and tested their potential to mediate protection by transfer experiments. Only the T cell line C4-N and the T cell line specific for the full-length N protein were protective. By contrast, all truncated N protein fragments elicited a humoral immune response and contained antigenic sites recognized by antibodies from diseased rats.


The reviewers were thinking wisely.


docid: iarmikle

title: Analysis of age-dependent resistance to murine coronavirus JHM infection in mice.

text: Resistance to intraperitoneal murine coronavirus JHM infection in mice develops with age. C3H mice were found to be fully susceptible up to the age of 20 days and resistant after 23 days of age. Protection of susceptible animals from death due to infection could be achieved by maternal antibodies or by transfer of spleen cells from immunized, but not from nonimmunized, donor mice. Lack of protection by transfer of unprimed adult spleen cells was not related to immunosuppression by the host. Moreover, resistance of adult mice could not be abrogated by application of lymphocytes from suckling mice, although immune suppression by other means did affect the resistance of adult animals. On the other hand, spleen cells from nonimmunized mice could be primed with inactivated JHM virus in suckling mice and protected these mice from death due to a subsequent virus infection. Thus, the outcome of infection with JHM virus in suckling and adult mice can be influenced by immunological events, but is not exclusively due to the different stages of immune competence.


title: Results of Laparoscopic Sleeve Gastrectomy in 541 Consecutive Patients with Low Baseline Body Mass Index (30-35 kg/m2).

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is currently the leading bariatric procedure and targets, among other obesity classes, patients with BMI 30-35 kg/m2, which are reaching alarming proportions. METHODS Between February 2010 and August 2015, data on 541 consecutive patients with BMI 30-35 kg/m2 undergoing LSG were prospectively collected and analyzed. RESULTS Mean age was 32 ± 8 years (13-65) and 419 (77.4 %) were women. Preoperative weight was 92.0 ± 8.8 kg (65-121) and BMI was 32.6 ± 1.5 kg/m2 (30-35). Comorbidities were detected in 210 (39 %) patients. Operative time was 74 ± 12 min (40-110) and postoperative stay was 1.7 ± 0.22 days (1-3). There were no deaths, leaks, abscesses or strictures and the rate of hemorrhage was 1.2 %. At 1 year, 98 % were followed and BMI decreased to 24.7 ± 1.6, the percentage of total weight loss (% TWL) was 24.1 ± 4.7 while the percentage of excess BMI loss (%EBMIL) reached 106.1 ± 24.1. At 5 years, 76 % of followed patients achieved a ≥50 % EBMIL. CONCLUSION With appropriate surgical expertise, LSG in patients with BMI 30-35 kg/m2 achieved excellent outcomes with a zero fistula rate.


title: Human macrophages are susceptible to coronavirus OC43.

text: Adherent adult and cord blood macrophages were infected with human coronavirus OC43 at a multiplicity of 1-1.5 and washed twice to remove unbound virus. Virus progeny was detected in the supernatant on day 1 and peaked at 2-3 days at an average titer of 5 +/- 3.9 x 10(6) pfu/ml from seven samples. Viral RNA was detected by nested set RT-PCR in infected macrophages incubated for 48 hr. Intracellular viral nucleocapsid was detected in 15% of the cells and surface staining for viral spike antigen was observed using monoclonal antibodies. Amplification of infectious virus and detection viral RNA and antigen synthesis in macrophages in vitro indicates susceptibility to OC43 virus.


title: Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein.

text: The coronavirus, mouse hepatitis virus strain JHM, causes acute and chronic neurological diseases in rodents. Here we demonstrate that two closely related virus variants, both of which cause acute encephalitis in susceptible strains of mice, cause markedly different diseases if mice are protected with a suboptimal amount of an anti-JHM neutralizing antibody. One strain, JHM.SD, caused acute encephalitis, while infection with JHM.IA resulted in no acute disease. Using recombinant virus technology, we found that the differences between the two viruses mapped to the spike (S) glycoprotein and that the two S proteins differed at four amino acids. By engineering viruses that differed by only one amino acid, we identified a serine-to-glycine change at position 310 of the S protein (S310G) that recapitulated the more neurovirulent phenotype. The increased neurovirulence mediated by the virus encoding glycine at position S310 was not associated with a different tropism within the central nervous system (CNS) but was associated with increased lateral spread in the CNS, leading to significantly higher brain viral titers. In vitro studies revealed that S310G was associated with decreased S1-S2 stability and with enhanced ability to mediate infection of cells lacking the primary receptor for JHM ("receptor-independent spread"). These enhanced fusogenic properties of viruses encoding a glycine at position 310 of the S protein may contribute to spread within the CNS, a tissue in which expression of conventional JHM receptors is low.


title: [SARS vaccines].

text: Severe acute respiratory syndrome (SARS) is an emerging disease derived from wild animals and is highly pathogenic with a high mortality. A novel coronavirus SARS coronavirus was identified to be a causative agent for SARS. Since its discovery, many trials have been executed to establish the prophylactic and therapeutics toward SARS using laboratory animals. A number of different types of vaccines, such as inactivated virus vaccine, subunit vaccine, DNA vaccine and vaccine using viral expression vector as well as attenuated live vaccine so far reported indicate that neutralizing antibodies play an important role for protection. However, vaccine applicable to humans with the high efficacy and safety has not yet been reported.


title: Metro Atlanta responds to West Nile virus: a coordinated public health response.

text: Three and a half million people live in metropolitan Atlanta, in multiple counties with varying population bases, resources, issues and separate boards of health. Historically, public health issues have been managed within each county, with very little sharing of information among counties. The 1999 West Nile virus (WNV) outbreak in the Northeast caused public health officials in Atlanta to recognize the potential for the disease to spread to Georgia and the need to develop a coordinated, multi-jurisdictional response plan. This plan would need to address a new disease with little scientific data to predict how it might behave in a new environment and would also require closely coordinated communication among the local/state public health entities and elected officials. In early 2000, staff from the five health districts in the metro Atlanta area and the state health department voluntarily convened the Metro Atlanta Surveillance Task Force (MASTF) to create the Metro Atlanta West Nile Virus Response Plan. This plan utilizes a coordinated effort encompassing public education, surveillance, and mosquito control. With this plan in place, when the first human case of WNV was detected in Atlanta, the public heard consistent health messages about preventive measures to lower their risk of illness and the metro counties were able to carry out a successful uniform approach to mosquito control. This plan has received recognition by the National Association of County and City Health Officials (NACCHO) as a 2004 Model Practice, demonstrating exemplary and replicable qualities in response to a local public health need. Since the early days of the emergence of WNV in the metro Atlanta area, MASTF has continued to be a viable, evolving entity, managing and anticipating health issues. The MASTF plan is a successful effort to develop consistent policies and procedures for disease surveillance in a heavily populated area with multiple local health departments.


title: IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections.

text: Profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type I IFN-dependent loss of CD8 T cells immediately preceding the development of the antiviral T cell response. Most memory (CD44(high)) and some naive (CD44(low)) CD8 T cells are susceptible to IFN-induced attrition, and we show in this study that the IFN-induced attrition of CD8(+)CD44(high) T cells is associated with elevated activation of caspase-3 and caspase-8. We questioned whether TCR engagement by Ag would render CD8 T cells resistant to attrition. We tested whether a high concentration of Ag (GP33 peptide) would protect lymphocytic choriomeningitis (LCMV)-specific naive CD8 T cells (TCR transgenic P14 cells specific for the GP33 epitope of LCMV) and memory CD8 T cells (GP33-specific LCMV-immune cells) from depletion. Both naive P14 and memory GP33-specific donor CD8 T cells decreased substantially 16 h after inoculation with the Toll receptor agonist and IFN inducer, poly(I:C), regardless of whether a high concentration of GP33 peptide was administered to host mice beforehand. Moreover, donor naive P14 and LCMV-specific memory cells were depleted from day 2 LCMV-infected hosts by 16 h posttransfer. These results indicate that Ag engagement does not protect CD8 T cells from the IFN-induced T cell attrition associated with viral infections. In addition, computer models indicated that early depletion of memory T cells may allow for the generation for a more diverse T cell response to infection by reducing the immunodomination caused by cross-reactive T cells.


title: A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo.

text: A deletion mutant of severe acute respiratory syndrome coronavirus (SARS-CoV) has been engineered by deleting the structural E gene in an infectious cDNA clone that was constructed as a bacterial artificial chromosome (BAC). The recombinant virus lacking the E gene (rSARS-CoV-DeltaE) was rescued in Vero E6 cells. The recovered deletion mutant grew in Vero E6, Huh-7, and CaCo-2 cells to titers 20-, 200-, and 200-fold lower than the recombinant wild-type virus, respectively, indicating that although the E protein has an effect on growth, it is not essential for virus replication. No differences in virion stability under a wide range of pH and temperature were detected between the deletion mutant and recombinant wild-type viruses. Although both viruses showed the same morphology by electron microscopy, the process of morphogenesis seemed to be less efficient with the defective virus than with the recombinant wild-type one. The rSARS-CoV-DeltaE virus replicated to titers 100- to 1,000-fold lower than the recombinant wild-type virus in the upper and lower respiratory tract of hamsters, and the lower viral load was accompanied by less inflammation in the lungs of hamsters infected with rSARS-CoV-DeltaE virus than with the recombinant wild-type virus. Therefore, the SARS-CoV that lacks the E gene is attenuated in hamsters, might be a safer research tool, and may be a good candidate for the development of a live attenuated SARS-CoV vaccine.


title: MicroRNA-Mediated Down-Regulation of Apoptosis Signal-Regulating Kinase 1 (ASK1) Attenuates the Apoptosis of Human Mesenchymal Stem Cells (MSCs) Transplanted into Infarcted Heart.

text: Stem cell therapy using adult stem cells, such as mesenchymal stem cells (MSCs) has produced some promising results in treating the damaged heart. However, the low survival rate of MSCs after transplantation is still one of the crucial factors that limit the therapeutic effect of stem cells. In the damaged heart, oxidative stress due to reactive oxygen species (ROS) production can cause the death of transplanted MSCs. Apoptosis signal-regulating kinase 1 (ASK1) has been implicated in the development of oxidative stress-related pathologic conditions. Thus, we hypothesized that down-regulation of ASK1 in human MSCs (hMSCs) might attenuate the post-transplantation death of MSCs. To test this hypothesis, we screened microRNAs (miRNAs) based on a miRNA-target prediction database and empirical data and investigated the anti-apoptotic effect of selected miRNAs on human adipose-derived stem cells (hASCs) and on rat myocardial infarction (MI) models. Our data indicated that miRNA-301a most significantly suppressed ASK1 expression in hASCs. Apoptosis-related genes were significantly down-regulated in miRNA-301a-enriched hASCs exposed to hypoxic conditions. Taken together, these data show that miRNA-mediated down-regulation of ASK1 protects MSCs during post-transplantation, leading to an increase in the efficacy of MSC-based cell therapy.


title: Psychosocial impact among the public of the severe acute respiratory syndrome epidemic in Taiwan.

text: During the 2003 outbreak, severe acute respiratory syndrome (SARS) spread to more than 30 countries. Not only did it cause severe health problems but it also imposed a great psychological impact on the public. SARS emerged in Taiwan during April 2003. This study investigates the psychosocial impact and the associated factors of depression of the SARS epidemic in Taiwan when the epidemic had just been controlled. A total of 1552 respondents were recruited in the study by random selection from the telephone book. Demographic data, SARS experience, self-perceived health state, neighborhood relationships, and depression were surveyed by telephone interviewing. Respondents were grouped as 'impacted group' and 'non-impacted group' according to whether they or their friends and family had been quarantined, or suspected of being infected. The psychosocial impact and associated factors were compared between the two groups. The 'impacted group' had higher depressive levels, poorer neighborhood relationships, poorer self-perceived health, and a higher economic impact than the 'non-impacted group'. The poorer self-perceived health and economic impact factors were associated with depression. The neighborhood relationship factor was negatively associated with depression for the 'impacted group', but not for the 'non-impacted group'. The 'impacted group' had experienced greater psychosocial impact possibly due to the SARS impact, the economic downturn, poor self-perceived health conditions, and decreased social support systems. An appropriate mental health intervention to improve the self-perceived health condition, to provide instrumental and psychological support for the 'impacted group', and to decrease the stigmatization and discrimination from the public could have buffered the psychological impact from this epidemic disaster.


title: Spatial and temporal analysis of human infection with avian influenza A(H7N9) virus in China, 2013.

text: Descriptive and geographic information system methods were used to depict the spatial and temporal characteristics of the outbreak of human infection with a novel avian influenza A(H7N9) virus in mainland China, the peak of which appeared between 28 March and 18 April 2013. As of 31 May 2013, there was a total of 131 reported human infections in China, with a cumulative mortality of 29% (38/131). The outbreak affected 10 provinces, with 106 of the cases being concentrated in the eastern coastal provinces of Zhejiang, Shanghai and Jiangsu. Statistically significant spatial clustering of cumulative human cases was identified by the Cuzick–Edwards’ k-nearest neighbour method. Three spatio-temporal clusters of cases were detected by space–time scan analysis. The principal cluster covered 18 counties in Zhejiang during 3 to 18 April (relative risk (RR): 26.39;p<0.0001), while two secondary clusters in March and April covered 21 counties along the provincial boundary between Shanghai and Jiangsu (RR: 6.35;p<0.0001) and two counties in Jiangsu (RR: 72.48;p=0.0025). The peak of the outbreak was in the eastern coastal provinces of Zhejiang, Shanghai and Jiangsu that was characterised by statistically significant spatio-temporal aggregation, with a particularly high incidence in March and April 2013.


docid: hcwgpvyh

title: 3C-like proteinase from SARS coronavirus catalyzes substrate hydrolysis by a general base mechanism.

text: SARS 3C-like proteinase has been proposed to be a key enzyme for drug design against SARS. Lack of a suitable assay has been a major hindrance for enzyme kinetic studies and a large-scale inhibitor screen for SARS 3CL proteinase. Since SARS 3CL proteinase belongs to the cysteine protease family (family C3 in clan CB) with a chymotrypsin fold, it is important to understand the catalytic mechanism of SARS 3CL proteinase to determine whether the proteolysis proceeds through a general base catalysis mechanism like chymotrypsin or an ion pair mechanism like papain. We have established a continuous colorimetric assay for SARS 3CL proteinase and applied it to study the enzyme catalytic mechanism. The proposed catalytic residues His41 and Cys145 were confirmed to be critical for catalysis by mutating to Ala, while the Cys145 to Ser mutation resulted in an active enzyme with a 40-fold lower activity. From the pH dependency of catalytic activity, the pK(a)'s for His41 and Cys145 in the wild-type enzyme were estimated to be 6.38 and 8.34, while the pK(a)'s for His41 and Ser145 in the C145S mutant were estimated to be 6.15 and 9.09, respectively. The C145S mutant has a normal isotope effect in D(2)O for general base catalysis, that is, reacts slower in D(2)O, while the wild-type enzyme shows an inverse isotope effect which may come from the lower activation enthalpy. The pK(a) values measured for the active site residues and the activity of the C145S mutant are consistent with a general base catalysis mechanism and cannot be explained by a thiolate-imidazolium ion pair model.


title: Getting more from less: algorithms for rapid protein identification with multiple short peptide sequences.

text: We describe two novel sequence similarity search algorithms, FASTS and FASTF, that use multiple short peptide sequences to identify homologous sequences in protein or DNA databases. FASTS searches with peptide sequences of unknown order, as obtained by mass spectrometry-based sequencing, evaluating all possible arrangements of the peptides. FASTF searches with mixed peptide sequences, as generated by Edman sequencing of unseparated mixtures of peptides. FASTF deconvolutes the mixture, using a greedy heuristic that allows rapid identification of high scoring alignments while reducing the total number of explored alternatives. Both algorithms use the heuristic FASTA comparison strategy to accelerate the search but use alignment probability, rather than similarity score, as the criterion for alignment optimality. Statistical estimates are calculated using an empirical correction to a theoretical probability. These calculated estimates were accurate within a factor of 10 for FASTS and 1000 for FASTF on our test dataset. FASTS requires only 15-20 total residues in three or four peptides to robustly identify homologues sharing 50% or greater protein sequence identity. FASTF requires about 25% more sequence data than FASTS for equivalent sensitivity, but additional sequence data are usually available from mixed Edman experiments. Thus, both algorithms can identify homologues that diverged 100 to 500 million years ago, allowing proteomic identification from organisms whose genomes have not been sequenced.


title: Acute Respiratory Distress Syndrome Secondary to Influenza A(H1N1)pdm09: Clinical Characteristics and Mortality Predictors.

text: BACKGROUND Acute respiratory distress syndrome secondary to influenza A(H1N1)pdm09 virus is the leading cause of death among this patient population. Expanding the knowledge of its course and predictors of mortality is relevant to decision making. We aimed to describe the clinical characteristics and identify factors associated with mortality in patients with acute respiratory distress syndrome secondary to influenza A(H1N1)pdm09 during the 2013-2014 influenza season. METHODS This is an observational study of a prospective cohort of 70 patients with acute respiratory distress syndrome and influenza A(H1N1) pdm09 seen in an academic medical center. Multivariate logistic regression was used to identify the independent mortality predictors. Bootstrap was used for internal model validation. RESULTS This cohort was represented by young adults (43 ± 11 years old). Obesity was present in 62.5% and was not associated with mortality. Mortality at 28 days and at discharge from the respiratory intensive care unit was 14 and 20%, respectively. All patients met the criteria for acute respiratory distress syndrome, 73% had vasodilatory shock, and 27.1% had acute kidney injury on respiratory intensive care unit admission. We observed a high incidence of intensive care unit-acquired weakness (81.4%). Ventilator-associated pneumonia developed in 47.1% and was not associated with mortality. In multivariate analysis, independent risk factors for intensive care unit mortality were age (odds ratio [OR] = 1.102), white blood cell count (OR = 1.22), and lactate dehydrogenase levels (OR = 1.004) on admission to the intensive care unit. CONCLUSIONS We described the clinical characteristics and course of a cohort of patients with acute respiratory distress syndrome secondary to influenza A(H1N1)pdm09, and developed a predictive model of mortality based on the covariates age, levels of lactate dehydrogenase, and white cell count on admission to the respiratory intensive care unit.


title: Retrieval of distorted pipeline embolic device using snare-loop.

text: BACKGROUND Flow-diverter stents are increasingly being used in the endovascular treatment of intracranial aneurysms. Because of this increased usage, the occurrence of stent malpositioning, intra-arterial distortion, or migration will likely increase as well. METHODS We describe the conformational twisting and deformity of a pipeline embolic device (PED) stent (Covidien, EV3) within the carotid artery during stent placement, with the subsequent immediate removal of the stent by using an endovascular snare-loop to successfully remove the device. RESULTS The PED can be successfully removed using a snare-loop device when indicated. In this case, following removal of the initial PED, the aneurysms can be successfully treated with the placement of a second PED. CONCLUSION It is critical to have a contingency plan for the removal of malpositioned or otherwise deformed stents that could potentially represent significant sources of iatrogenic stroke.


Global health science: a threat and an opportunity for collaborative clinical science.


Opportunistic Infections in Research Rodents: The Challenges Are Great and the Hour is Late.


title: Receptor-dependent coronavirus infection of dendritic cells.

text: In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway.


title: Primary Stenting for Acute Ischemic Stroke Using the Enterprise Intracranial Stent: 2-Year Results of a Phase-I Trial.

text: BACKGROUND The preliminary results of a prospective consecutive series of 20 patients who underwent Enterprise-assisted recanalization for acute ischemic stroke were recently reported. Recanalization to thrombolysis in myocardial infarction (TIMI) grade 2 (n = 6) or 3 (n = 12) flow was achieved in 18 patients (90% revascularization rate). Good outcome (modified Rankin Scale [mRS] score of ≤2) was obtained in 10 patients (50%) at 30 days. Here, we report the 2-year clinical follow-up data for patients enrolled in that prospective study. METHODS Study patients were scheduled for examinations 2 years postprocedure at which time mRS and Barthel indices were obtained. RESULTS Among 12 survivors at 2 years, 11 of the 20 (55%) study patients improved to mRS score ≤2 and 1 (5%) patient was disabled with an mRS 4. Of the 11 patients with mRS 0-2 scores, 10 patients had a Barthel index of 100, and the 11th had a Barthel index of 95. One patient improved from mRS 3 to 2 during the interval between the 6- and 12-month postintervention evaluations after intervention. Eight of 13 (62%) survivors underwent follow-up imaging at 6 months without evidence of instent stenosis or thrombosis. CONCLUSION At 2 years of follow-up, improvement in quality of life after acute stroke intervention was sustained; and 11 of 12 (92%) survivors had an excellent functional outcome. Improvement in functional status can occur even up to 1 year after stroke intervention. These results 2 years after acute stroke intervention demonstrate sustained benefit from acute intervention. ABBREVIATIONS AISacute ischemic strokeCTcomputed tomographicFDAFood and Drug AdministrationIVintravenousMCAmiddle cerebral arterymRSmodified Rankin ScaleNIHSSNational Institutes of Health Stroke Scale ScoreSWIFTSolitaire FR With the Intention For Thrombectomy (SWIFT)TIMIthrombolysis in myocardial infarctiontPAtissue plasminogen activatorTREVOThrombectomy REvascularization of large Vessel Occlusions.


Vivax Malaria: Benign No More.


title: Dot-blot hybridization using digoxigenin-labeled cDNA probe complementary to the S1 gene of avian infectious bronchitis virus permits discrimination between virus strains.

text: Digoxigenin-dUTP-labeled DNA probe was prepared from a cDNA clone complementary to the gene encoding S1 region of the spike protein of infectious bronchitis coronavirus (IBV) strain M41. The probe exclusively reacted with four strains at 56 degrees C which were grouped to the same serotype as the strain used for the probe. In contrast, at 68 degrees C, the probe reacted only with the homologous strain and did not react even with the strains belonging to the same serotype. The dot-blot hybridization thus appeared serotype-specific at 56 degrees C and strain-specific at 68 degrees C. In addition, it was revealed that the S1 gene has some nucleotide sequence variation even among strains in the same serotype. This technique should be applied to determining serotypes of the virus isolates and to differentiating field isolates from the vaccine strain.


title: [Epidemiology of viral nosocomial infections in pediatrics].

text: Nosocomial viral infections account for at least 5% of the total of NI and reach 23% in pediatric wards. The nosocomial infection (NI) incidence rate varies from 0.59 to 0.72 per 100 patients in pediatric wards. Many viruses have been associated with NI in pediatric wards. Rotavirus and respiratory syncytial virus (RSV) are the most frequent. Other viruses frequently identified are: calicivirus, adenovirus, astrovirus, influenza et para-influenza, rhinovirus and coronavirus. Asymptomatic infections occur frequently. The period of communicability varies and depends on the virus. It often begins before the clinical signs appear and ends after the healing. Viral shedding may be intermittent. Children and hospital environment and less frequently hospital staff are the main source for the virus. Poor handwashing results in direct spread to patient or self-inoculation even for respiratory viruses like RSV and rhinovirus. The main risk factors for NI are prolonged hospital stay, past history of prematurity and low age. Immunocompromised patients constitute a special high-risk group. Understaffing is also a risk factor. Minimal infective doses depend on the route of inoculation and the kind of virus. Low doses are for example sufficient for rotavirus, adenovirus and calicivirus. Viral inactivation is all the more easy when there is an envelope. Handwashing and appropriate isolation (technical and geographical) are the mainstay of prevention of viral NI. Vaccines are promising, especially for rotavirus.


title: International comparisons in critical care: a necessity and challenge.

text: PURPOSE OF REVIEW Understanding variation in critical care resources, and delivery of care between countries will allow for improved disaster planning, evaluation of research findings, and assessment of the utility of critical care itself. This review describes the available data for international comparisons and the many factors that need to be addressed for an appropriate interpretation of results. RECENT FINDINGS Recent studies on subgroups of critical care patients include data from many different countries. These new studies provide important information on the overall incidence of these disease states, but most of these international studies do not take into account the critical care resources of the countries being discussed. For an appropriate interpretation of findings the relevant baseline critical care resources, prevalence of diseases, and cultural practices, need to be quantified. The existence of these other factors prevents the use of a severity of illness scoring system alone to account for differences between countries. SUMMARY Many recent critical care studies include data from multiple countries. With continued movement towards international studies, and improvements in data collection systems, comparisons between countries are becoming easier. These findings need to be interpreted in the context of all the relevant country information.


title: [Expression of the monoclonal antibody against nucleocapsid antigen of SARS-associated coronavirus in autopsy tissues from SARS patients].

text: OBJECTIVE To investigate the presence and distribution of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in autopsy tissues obtained from patients died of SARS. METHODS Immunohistochemical technique was applied in 4 fatal SARS cases to examine the autopsy tissues including the lungs, spleen, lymph nodes, brain, pituitary, heart, liver, kidney, pancreas, trachea, esophagus, gastrointestinal tract, adrenal glands, parathyroids, skin and bone marrow. RESULTS Immunohistochemistry identified positive monoclonal antibody against SARS-CoV nuceeocapsid (N) protein in the alveolar epithelium and the infiltrating monocytes or macrophages in the lung, spleen and lymph nodes; the presence of the antibody was also detected in the serous gland epithelium of the trachea/bronchus, squamous epithelium of the esophagus, the gastric parietal cells, the epithelium of the intestinal tract, acidophilic cells in the parathyroids and pituitary, acinus cells in the pancreas, adrenal cortical cells, sweat gland cells, small vessel endothelium, bone marrow promyelocytes, epithelial cells of the distal convoluted tubule of the kidney, brain neurons, and the hepatocytes near the central vein. CONCLUSIONS A variety of organs and tissues can be infected by SARS-CoV, and the positive expression of SARS-CoV N protein in the epithelial cells of the gastrointestinal tract, the distal convoluted tubule of the kidney and the sweat gland cells is significant for studying the transmission routes of SARS.


title: ['Severe acute respiratory syndrome' (SARS): epidemiology, clinical signs, diagnosis and prevention].

text: Severe acute respiratory syndrome (SARS) is caused by a recently identified Coronavirus (SARS-CoV). The clinical symptoms are non-specific and during the first few days in particular, are not clinically distinguishable from those of many other viral or bacterial infections. The majority of infected patients develop pneumonia within a week of the first symptoms appearing. Since November 2002 the virus has spread from South China to almost 30 other countries, where about 8500 infected individuals have been registered; about 800 people have already died from the disease (9.5%). The number of infected persons includes a noticeably high percentage of health workers. This fact underlines the importance of good infection prevention measures for each patient contact. The implementation of hygienic measures requires attention, because the infection of personnel in Toronto hospitals still occurred after the virus and transmission routes were known. It appears that transmission can be prevented with relatively simple precautions, as long as these are consistently implemented. Early recognition and isolation of a possible source are an essential part of this. SARS is a group A notifiable disease (report if suspected). In the Netherlands the general practitioner has a prominent role in assessing and treating individuals who are infected or might be infected with SARS-CoV. A protocol and a detailed action plan are available. In addition to this hospitals should be prepared for the initial reception of a patient with SARS, who presents directly to the outpatients' clinic or Casualty Department.


title: Prevention and control of emerging infections: a challenge for the 3rd millennium.

text: In the last 30 years, several emerging infections due to novel viruses have been identified, from haemorrhagic fever viruses to HIV, from the SARS-Coronavirus to Avian influenza viruses. Ecological and genetic changes are important determinants of the emergence of new viral infections, driving to an increase of R0 (the basic reproductive number) through increasing the probability of transmission. The current H5N1 epidemic may be considered a prepandemic paradigm that needs thorough investigation.


title: Rapid diagnosis by electron microscopy of avian coronavirus infection.

text: The election microscopic examination of allantoic fluid from embryonated hens' eggs inoculated with tissue homogenates from organs of birds suffering with infectious bronchitis, reveals the presence of coronaviruses as early as the first or the second passage. This method permits a rapid diagnosis and is as accurate as the standard technique.


docid: bbtdqoar

title: Non-technical skills in minimally invasive surgery teams: a systematic review.

text: BACKGROUND Root cause analyses show that up to 70 % of adverse events are caused by human error. Strong non-technical skills (NTS) can prevent or reduce these errors, considerable numbers of which occur in the operating theatre. Minimally invasive surgery (MIS) requires manipulation of more complex equipment than open procedures, likely requiring a different set of NTS for each kind of team. The aims of this study were to identify the MIS teams' key NTS and investigate the effect of training and assessment of NTS on MIS teams. METHODS The databases of PubMed, Cochrane Library, Embase, PsycINFO, and Scopus were systematically searched according to Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles containing outcome measures related to MIS teams' key NTS, training, or assessment of NTS were included. RESULTS The search yielded 1984 articles, 11 of which were included. All were observational studies without blinding, and they differed in aims, types of evaluation, and outcomes. Only two studies evaluated patient outcomes other than operative time, and overall, the studies' quality of evidence was low. Different communication types were encountered in MIS compared to open surgery, mainly due to equipment- and patient-related challenges. Fixed teams improved teamwork and safety levels, while deficient planning and poor teamwork were found to obstruct workflow and increase errors. Training NTS mitigates these issues and improves staff attitudes towards NTS. CONCLUSIONS MIS teams' NTS are important for workflow and prevention of errors and can be enhanced by working in fixed teams. In the technological complex sphere of MIS, communication revolves around equipment- and patient-related topics, much more so than in open surgery. In all, only a few heterogeneous-design studies have examined this. In the future, the focus should shift to systematically identifying key NTS and developing effective, evidence-based team training programmes in MIS.


title: Knowledge, attitude and practice towards SARS.

text: The objective of the study was to explore the knowledge, attitude and practice of the population of Qatar towards severe acute respiratory syndrome (SARS). The study took the form of a cross-sectional community-based survey in Doha International Airport and primary health care centres situated in urban and semi-urban areas of Qatar. The survey was conducted among travellers arriving at Doha International Airport and community residents visiting health centres from April to September 2003. A total of 1,800 subjects were approached for the study of which 1,386 (77.0%) responded to the questionnaire. The study showed that although 79.4% of the total subjects claimed to know about SARS, only 8.0% had accurate knowledge about all of the symptoms of SARS. The respondents' satisfaction with the preventive measures taken by the health authorities was only 66.6%. Overall, 73.0% of the total subjects knew that SARS was highly infectious; 69.9% knew that it could spread through close contact; 67.4% were aware that high fever was the early symptom; and 60.8% thought SARS could be cured. Half of the subjects said they had gained most of their knowledge on SARS through television and radio programmes (52.2%). Three-fifths (60.1%) were afraid to travel for fear of being affected by SARS. The level of awareness of SARS among Qataris was poor (31.7%) compared to that among non-Qataris (68.3%). The level of knowledge about SARS was better among educated subjects. The survey found a high level of stress and fear among the respondents. Health authorities should be on the alert and re-examine their capacity to manage an outbreak like SARS in the event that such a mishap should recur in the future.


title: Infectious diarrhea in developed and developing countries.

text: Diarrhea from gastrointestinal infection remains a common problem. In industrialized countries, management is aimed at reducing morbidity and defining groups that may benefit from further investigation. Most infectious diarrhea is self-limiting and only requires supportive management. Viral agents are increasingly recognized as causative agents of epidemic and sporadic diarrhea. In developing countries, diarrhea is a major cause of mortality in children. Oral rehydration therapy, guided by a clinical assessment of the degree of dehydration, is cheap, simple, and effective and remains the mainstay of management of infant diarrhea. Controversies focus on the optimal formulation of oral rehydration solution. A vaccine against rotavirus has the potential to save millions of lives worldwide.


title: Proteolytic cleavage of the murine coronavirus surface glycoprotein is not required for its fusion activity.

text: The surface glycoprotein (S) of the murine hepatitis coronavirus MHV normally undergoes proteolytic cleavage during transport to the cell surface. To determine whether the cleavage of the MHV-JHM S glycoprotein is required to activate its ability to fuse cellular membranes, the protease recognition sequence in a cDNA copy of the S gene was altered from Arg-Arg-Ala-Arg-Arg into Ser-Val-Ser-Gly-Gly by site directed mutagenesis. The mutated and wild type S genes were expressed by means of recombinant vaccinia viruses and it could be shown that the mutated S protein was not cleaved when it was expressed in mouse DBT cells, in contrast to the wild type S protein. Nevertheless, the non-cleaved S protein induced extensive syncytium formation in mouse DBT cells. These results clearly indicate that the non-cleaved form of the MHV S protein is able to mediate cell membrane fusion. Thus, proteolytic cleavage is not an absolute requirement for its fusion function.


title: High affinity interaction between nucleocapsid protein and leader/intergenic sequence of mouse hepatitis virus RNA.

text: The nucleocapsid (N) protein of mouse hepatitis virus (MHV) is the major virion structural protein. It associates with both viral genomic RNA and subgenomic mRNAs and has structural and non-structural roles in replication including viral RNA-dependent RNA transcription, genome replication, encapsidation and translation. These processes all involve RNA-protein interactions between the N protein and viral RNAs. To better understand the RNA-binding properties of this multifunctional protein, the N protein was expressed in Escherichia coli as a chimeric protein fused to glutathione-S-transferase (GST). Biochemical analyses of RNA-binding properties were performed on full-length and partial N protein segments to define the RNA-binding domain. The full-length N protein and the GST-N protein fusion product had similar binding activities with a dissociation constant (K(d)) of 14 nM when the MHV 5'-leader sequence was used as ligand. The smallest N protein fragment which retained RNA-binding activity was a 55 aa segment containing residues 177-231 which bound viral RNA with a K(d) of 32 nM. A consensus viral sequence recognized by the N protein was inferred from these studies; AAUCYAAAC was identified to be the potential minimum ligand for the N protein. Although the core UCYAA sequence is often tandemly repeated in viral genomes, ligands containing one or more repeats of UCYAA showed no difference in binding to the N protein. Together these data demonstrate a high-affinity, specific interaction between the N protein and a conserved RNA sequence present at the 5'-ends of MHV mRNA.


docid: liemgysl

title: Australian Senate votes to allow therapeutic cloning.


docid: uvvfjckv

title: Automated Analysis of Public Health Laboratory Test Results.

text: This study investigates the use of machine learning methods for classifying and extracting structured information from laboratory reports stored as semi-structured point-form English text. This is a novel data format that has not been evaluated in conjunction with machine learning classifiers in previous literature. Our classifiers achieve human-level predictive accuracy on the binary Test Performed and 4-class Test Outcome labels. We consider symbolic approaches for predicting the highly multi-class Organism Genus and Organism Species labels. Results are discussed from the viewpoint of interpretability and generalizability to new incoming laboratory reports. Code has been made public at https://github.com/enchainingrealm/UbcDssgBccdc-Research/tree/master/src.


Is reporting many cases of COVID-19 in Iran due to strength or weakness of Iran's health system?


title: Laparoscopic mesh fixation using laser-assisted tissue soldering in a porcine model.

text: BACKGROUND AND OBJECTIVE Animal studies using open surgical models indicate that collagen solder is capable of fixation of surgical meshes without interfering with tissue integration, increasing adhesions, or increasing inflammation intraperitoneally. This study describes development of instrumentation and techniques for laparoscopic herniorrhaphy using laser-assisted soldering technology. STUDY DESIGN AND METHODS Anesthetized 20 kg to 25 kg female Yorkshire pigs underwent laparoscopy with a 3-trocar technique. Parietex TET, Parietex TEC, and Prolene mesh segments (5 x 5 cm) were embedded in 55% collagen solder. Segments were inserted by using a specially designed introducer and affixed to the peritoneum by using prototype laser devices (1.45 micro, 4.5 W continuous wave, 5-mm spot, 55 degrees C set temperature) and a custom laparoscopic handpiece (IPOM). Parietex PCO mesh was inserted and affixed using the Endo-hernia stapler (Control). Animals were recovered and underwent second-look laparoscopy at 6 weeks. Mesh sites were harvested after animals were euthanized. RESULTS The mesh-solder constructs were easily inserted and affixed in an IPOM approach. Prolene mesh tended to curl at its edges as the solder was melted. Postoperative healing was similar to that in Control segments in all cases. DISCUSSION AND CONCLUSION Collagen-based tissue soldering permits normal wound healing and may mitigate or reduce the use of staples or other foreign bodies for laparoscopic mesh fixation, prevent tissue ischemia and possibly nerve entrapment, which result in severe postoperative pain and morbidity. Laser-assisted mesh fixation is a promising alternative for laparoscopic herniorrhaphy. Further development of this strategy is warranted.


The Association of Physicians of Great Britain and Ireland 1992.


title: Estimates of the reproduction numbers of Spanish influenza using morbidity data.

text: BACKGROUND There have been several studies of the transmissibility of the 1918 (Spanish) influenza virus, which has attributed to >20 million deaths. Many of the analyses to date have involved fitting predictions from a transmission model to the observed epidemic curves from different settings. METHODS Using morbidity data from cities in Europe and America and from confined settings during the 1918 influenza pandemic, we contrast the use of several different methods based on the growth rate and final size of the epidemic, which do not rely on transmission models, to estimate the effective and basic reproduction numbers. RESULTS The effective reproduction number (the average number of secondary infectious cases produced by a typical infectious case in a given population) for the 1918 influenza virus was in the range 1.2-3.0 and 2.1-7.5 for community-based and confined settings, respectively. CONCLUSIONS Assuming further that 30 and 50% of individuals were immune to Spanish influenza after the wave in April 1918 and the first subsequent wave, respectively, these findings imply that, in a totally susceptible population, an infectious case could have led to 2.4-4.3 and 2.6-10.6 cases in community-based and confined settings, respectively. These findings for community-based populations confirm the relatively low transmissibility of the 1918 (Spanish) influenza virus, which has been found by other studies using alternative data sources and methods.


title: Patient Age and the Outcomes after Decompressive Hemicraniectomy for Stroke: A Nationwide Inpatient Sample Analysis.

text: BACKGROUND Decompressive hemicraniectomy (DHC) for space-occupying cerebral infarction in older adults remains controversial, and there are limited nationwide data evaluating the outcomes after craniectomy for stroke by patient age. METHODS Patients who underwent DHC for ischemic stroke were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable logistic regression examined in-hospital mortality and a poor outcome (death, tracheostomy and gastrostomy, or discharge to institutional care). Covariates included year of admission, comorbidities, severity indices, and treatment variables (including the timing of decompression). RESULTS Craniectomy was performed in 1673 patients: 62.4 % were aged 18-60 years, 20.6 % aged 61-70 years, and 17.0 % aged greater than 70 years. DHC was associated with reduced adjusted odds of in-hospital death compared with medical treatment alone among patients with cerebral edema in all age categories, including those older than 70 years (p ≤ 0.008). However, among surgical patients, the adjusted odds of mortality were significantly greater for patients aged 61-70 (30.7 %, p = 0.02) and greater than 70 years (34.5 %, p = 0.02), but not different for patients aged 51-60 (22.8 %), compared to those aged 18-50 years (19.7 %). The adjusted odds of a poor outcome also increased significantly with age, particularly for patients greater than 60 years. CONCLUSION In this nationwide analysis, DHC was associated with reduced mortality regardless of patient age, including among those aged greater than 70 years. However, patients aged greater than 60 years treated surgically experienced higher odds of mortality (32.4 %), discharge to institutional care (47.1 %), and a poor outcome (77.0 %) compared with younger patients.


title: Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines.

text: The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.


title: Malnutrition and infection: an update.

text: The original Scrimshaw, Taylor and Gordon conceptual framework for the interaction of nutrition and infection has well served the scientific community for almost half a century. At its core is the notion of synergistic (mutually reinforcing) and antagonistic (mutually nullifying) influences of the malnourished state on infectious conditions and vice versa. Research on a series of advancing fronts, however, has allowed the incorporation of both relevant public health issues (parasitosis, emerging infectious diseases, obesity and overweight, etc.) and advancing science (molecular immunology, oxidation biology, multiple micronutrient deficiencies, etc.). The present review is an interpretative update on close to 50 years of demographic and epidemiological evolution in the field of human nutrition and the implications for the interaction in the context of microbiological and immunological developments on the infectious side of the dialectic.


title: [The effect of central anatomical single-bundle versus anatomical double-bundle reconstruction of the anterior cruciate ligament on knee stability. a clinical study].

text: PURPOSE OF THE STUDY A comparison of the efficacy of central anatomical single-bundle (CASB) reconstruction with that of double-bundle (DB) repair of the anterior cruciate ligament (ACL) in relation to knee stability in anteroposterior translation (APT), internal rotation (IR) and external rotation (ER) of the joint. MATERIAL AND METHODS A total of 40 patients were evaluated; 20 had ACL reconstruction by the CASB technique using hamstrings and 20 underwent DB repair surgery. The average age was 31.3 years, and the group included 22 men and 18 women with 19 right and 21 left knees. The KT-1000 test was used to assess the amount of APT in the knee and rotational deviations were measured by the Rolimeter. In the DB patients, measurements were performed before surgery (on joints with ACL injury), then after reconstruction of the anteromedial (AM) or the posterolateral (PL) bundle and subsequently after repair of both ACL bundles. The CASB patients were assessed before and after graft insertion. RESULTS The average APT value was 18.5 mm for the pre-operative knees and it fell to 8.9 mm after AM bundle reconstruction. However, when the PL bundle was inserted in the first place, the average APT value was 13.1 mm only. The average values recorded after the DB and CASB reconstructions were 6.1 mm and 9.1 mm, respectively. The average IR range of motion in the pre-operative joints was 18.6 degrees. After AM bundle reconstruction it was 13.9 degrees and after PL bundle repair it was 15.3 degrees. In DB reconstruction the average IR value achieved 10.4 degrees, and in CASB repair surgery it was 13.7 degrees. The average ER range of motion in the pre-operative joints was 17.8 degrees. After AM bundle reconstruction it was 14.5 degrees and after PL bundle repair it was 14.9 degrees. In DB reconstruction the average ER value achieved 11.4 degrees, and in CASB repair surgery it was 14.5 degrees. DISCUSSION Rotational stability of the knee after ACL reconstruction is one of the most important factors in restoring physiological kinematics of the joint after ACL injury. Since there are not many studies comparing knee rotational stability after CASB with that after DB reconstructions, the results presented here may contribute to selecting the optimal method of ACL reconstruction. CONCLUSIONS The results show that, in ACL reconstruction, the DB technique provides better stability to the knee, in both APT and rotation, than the CASB method. The latter has the same effect on knee stability as the presence of the AM bundle alone. When the PL bundle is added, knee stability, in both APT and internal/external rotation, is increased in comparison with central single-bundle ACL repair. Key words:anterior cruciate ligament, navigation, central anatomical single-bundle reconstruction, double-bundle reconstruction.


title: What next in necrotizing enterocolitis?

text: Necrotizing enterocolitis (NEC) is a devastating disease of premature infants, with a mortality rate of 10-50%. It is uncommon in term infants and in premature infants who have not yet been fed. Most commonly NEC develops suddenly in a preterm infant who was otherwise well, with initial symptoms of abdominal distention, bilious or bloody emesis or gastric aspirates, hematochezia, and pneumatosis intestinalis, and sometimes progresses quickly to include bowel perforation, acidosis, shock, and death. Trigger factors (i.e. perinatal hypoxia, mild infection or formula feeding) cause focal mild intestinal mucosal injury. In the presence of proliferation of commensal bacteria, local breakdown of mucosal barrier may cause entry of bacterial products (e.g. lipopolysaccharides, platelet-activating factor). Endothelial platelet-activating factor and/or tumor necrotizing factor and/or direct stimulating effects of polymorphonuclear leukocytes cause proinflammatory cascade and focal necrosis, which increase the entry of large amounts of bacterial toxins, and then severe NEC, sepsis, and shock develop. Therapies for the prevention of NEC that appear to have some benefit are breastfeeding and antenatal steroids, and probably probiotics. Enteral immunoglobulin, polyunsaturated fatty acids, and arginine or glutamine supplementation are therapies for the prevention of NEC that do not appear to be of benefit. Enteral erythropoietin and enteral granulocyte colony-stimulating factor are promising novel therapies. Treatment options are limited to gut rest, parenteral nutrition, broad-spectrum antibiotics, and surgical interventions for enteral perforation. Two commonly used methods for NEC with intestinal perforation are laparotomy or primary peritoneal drainage ("patch, drain and wait"); however, the preferred method is controversial.


title: Diffuse alveolar lesion in BALB/c mice induced with human reovirus BYD1 strain and its potential relation with SARS.

text: The objective of this study was to investigate the pathogenicity and associated lesions of a new reovirus (ReoV) isolated from patients with Severe Acute Respiratory Syndrome (SARS) in China. Twenty-five four-week-old BALB/c female mice inoculated intranasally with either ReoV (strain BYD1) alone, or ReoV combined with SARS-CoV (strain BJF) displayed ejecting fur and loss of body weight compared with control animals. ReoV and SARS-CoV were isolated from most postmortem tissues. The histopathological features of ReoV infected animals consisted of diffuse alveolar damage, with scattered hemorrhage, hyaline membrane formation and interstitial pneumonia. A typical type II pneumocyte hyperplasia and fibrogranulomatous tissue formation in the alveolar septae were observed both in the animals inoculated simultaneously with these two viruses and in the animals inoculated firstly with SARS-CoV, followed by ReoV. The animals inoculated firstly with ReoV, followed with SARS-CoV displayed scattered hemorrhage in the alveolar septa. Furthermore, other lesions in above two combination groups included depletion of lymphocytes in the germinal center of lymph nodes in the lung hilus and the spleen, hemorrhagic necrosis in white pulp of spleen, hydroid degeneration, and fatty degeneration in the liver and kidney. Mice induced with SARS-CoV alone did not display clinical signs, characteristically hyaline membrane formation, hemorrhage and early pulmonary fibrosis in lung tissue. This study demonstrated that the newly isolated ReoV might be a virulent pathogen for BALB/c mice. Mice infected firstly with SARS-CoV, followed with ReoV developed a typical diffuse alveolar lesion.


title: S1 gene characteristics and efficacy of vaccination against infectious bronchitis virus field isolates from the United States and Israel (1996 to 2000).

text: The S1 genes of isolates of avian coronavirus infectious bronchitis virus (IBV) from commercial chickens in the US and Israel (20 isolates from each country) were studied using reverse transcription-polymerase chain reaction restriction fragment length polymorphism and sequencing. Partial sequences spanning the amino terminus region of S1 from amino acid residues 48 to 219, based on the Beaudette strain, were used for analysis. Phylogenetic clustering and high-sequence identity values were used to identify isolates that appeared to be derived from live IBV vaccines used in the two countries. Novel variant strains, unrelated by S1 sequencing and restriction fragment length polymorphism analyses to reference and vaccine strains, were also identified. Based on S1 sequence identity to available vaccines, the potential to use vaccination to control IBV infections was evaluated. Vaccination with commercial live strains Massachusetts (Mass), Arkansas (Ark) or DE/072/92, generally produced immunity against vaccine-related field isolates displaying high S1 sequence similarities (> or = 90%) to the respective vaccine strains. Immunization with a bivalent vaccine containing the Mass and Ark strains provided good cross-protection, averaging 81% against challenge with five variant isolates from the US having amino acid identity values ranging from 62 to 69% to Mass and from 68 to 83% to Ark, respectively. In contrast, the H120 vaccine strain induced low levels of protection, ranging from 25 to 58% against variant field isolates from Israel with amino acid identity values from 65 to 67%.


title: Transmission of viral respiratory infections in the home.

text: Respiratory viruses in the home exploit multiple modes of transmission. RSV is transmitted primarily by contact with ill children and contaminated objects in the environment. Influenza appears to be spread mainly by airborne droplet nuclei. Despite many years of study, from the plains of Salisbury, to the hills of Virginia, to the collegiate environment of Madison, WI, the precise routes rhinovirus takes to inflict the misery of the common cold on a susceptible population remain controversial.


title: Serological, colostral and milk responses of cows vaccinated with a single dose of a combined vaccine against rotavirus, coronavirus and Escherichia coli F5 (K99).

text: Twenty-five Ayrshire/Friesian cows were vaccinated once with a new combined vaccine against rotavirus, coronavirus and Escherichia coli F5 (K99) or given a saline placebo 31 days before the first expected calving date. Blood samples were taken from the cows at intervals from vaccination until seven days after calving and from their calves up to 28 days after birth, and colostrum and milk samples were collected from the cows at intervals for 28 days after calving. There was a significant increase in the mean specific antibody titre against all three antigens in the serum of the vaccinated animals (even in the presence of pre-existing antibody) which was accompanied by increased levels of protective antibodies to rotavirus, coronavirus and E coli F5 (K99) in their colostrum and milk for at least 28 days.


title: Current status of veterinary vaccines.

text: The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases.


title: Limitations of current prophylaxis against influenza virus infection.

text: Avian influenza has been a source of worldwide concern since Hong Kong authorities detected the first outbreak in 1997. Mainly as a result of poultry-to-human transmission, more than 200 cases of infection in humans have been attributed to the A/H5, A/H7, and A/H9 viral subtypes, with a case fatality rate for A/H5N1 infections exceeding 50%. A mutant or reassortant virus capable of efficient human-to-human transmission can set off a pandemic. Increased attention to prophylaxis against viral infection has identified several potentially complementary approaches: nonpharmacologic measures (eg, travel restrictions), vaccination, chemotherapeutic agents, and herbal/natural products. All have significant limitations that point out the need for additional modalities. Herbal/natural products, particularly those based on green tea extract, offer promise as adjuncts or alternatives to current interventions and warrant further evaluation in well-controlled human trials.


title: [Epidemiological profile of pandemic influenza A cases in the south of Santa Catarina state, Brazil, in 2009].

text: OBJECTIVE To describe the epidemiological features of influenza A (H1N1) cases in 14 municipalities of Santa Catarina, Brazil, during the 2009 pandemic. METHOD This cross-sectional study focused on suspected cases of H1N1 reported to the 20th Santa Catarina State Health Administration during the 2009 pandemic between July to September. Data were collected by epidemiological surveillance officers from the Brazilian communicable diseases information system SINAN. H1N1 cases were confirmed by laboratory testing (positive RT-PCR) or signs and symptoms characteristic of severe acute respiratory syndrome. RESULTS During the pandemic period, 1 149 suspected cases of influenza A were notified, of which 560 (48.6%) were confirmed. That translated into an incidence of 241.9/100 000 population. Mean age for confirmed cases was 29.5 ± 17.1 years, vs. 32.2 ± 20 years for those ruled out (P = 0.03). Of the total confirmed cases, 37.1% were hospitalized, with a hospital incidence rate of 89.9/100 000 people and lethality rate of 5.6/100 000 population. Age < 30 years, symptoms of fever, cough and dyspnea, and death were independently associated with influenza A infection (P < 0.05). There were no associations between confirmed cases and any comorbidities. CONCLUSION The studied sample differed from the national profile of influenza A cases in Brazil by the absence of associated comorbidities. However, it was similar to the national profile in terms of the young age of cases and the significant association with fever, cough, and dyspnea. An extension of the annual immunization campaign (currently focused on risk groups) to the overall population should be considered.


title: Bacteria as potential tools in bioterrorism, with an emphasis on bacterial toxins.

text: The threat of bioterrorism remains a reality worldwide and, although of low probability, an attack would be a high-consequence event. Microbes are available to individuals with appropriate contacts and even many low-grade bacterial pathogens can severely affect health. Toxins provide bacteria with a system of defence that is often detrimental to humans and their versatility makes them potential tools of bioterrorism. It should be remembered that the aim of terrorism is not always to kill but rather to strike fear into peoples lives. Therefore, agents such as botulinum and cholera toxin could be used, which may not cause significant mortality but would cause widespread panic and potentially high morbidity. Importantly, no state can ever be fully prepared for a response and it is probable that no state ever could be. It is for this reason that biological agents are so attractive as weapons.