title: Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children.

text: OBJECTIVE Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion. RESULTS BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously. EFFICACY Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively). SAFETY There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months. CONCLUSIONS Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.


docid: jmhhfpym

title: Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: implications for the development of vaccines and antiviral agents.

text: The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) interacts with cellular receptors to mediate membrane fusion, allowing viral entry into host cells; hence it is recognized as the primary target of neutralizing antibodies, and therefore knowledge of antigenic determinants that can elicit neutralizing antibodies could be beneficial for the development of a protective vaccine. Here, we expressed five different fragments of S, covering the entire ectodomain (amino acids 48 to 1192), as glutathione S-transferase fusion proteins in Escherichia coli and used the purified proteins to raise antibodies in rabbits. By Western blot analysis and immunoprecipitation experiments, we showed that all the antibodies are specific and highly sensitive to both the native and denatured forms of the full-length S protein expressed in virus-infected cells and transfected cells, respectively. Indirect immunofluorescence performed on fixed but unpermeabilized cells showed that these antibodies can recognize the mature form of S on the cell surface. All the antibodies were also able to detect the maturation of the 200-kDa form of S to the 210-kDa form by pulse-chase experiments. When the antibodies were tested for their ability to inhibit SARS-CoV propagation in Vero E6 culture, it was found that the anti-SDelta10 antibody, which was targeted to amino acid residues 1029 to 1192 of S, which include heptad repeat 2, has strong neutralizing activities, suggesting that this region of S carries neutralizing epitopes and is very important for virus entry into cells.


title: Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses.

text: Murine coronaviruses such as mouse hepatitis virus (MHV) infect mouse cells via cellular receptors that are isoforms of biliary glycoprotein (Bgp) of the carcinoembryonic antigen gene family (G. S. Dveksler, C. W. Dieffenbach, C. B. Cardellichio, K. McCuaig, M. N. Pensiero, G.-S. Jiang, N. Beauchemin, and K. V. Holmes, J. Virol. 67:1-8, 1993). The Bgp isoforms are generated through alternative splicing of the mouse Bgp1 gene that has two allelic forms called MHVR (or mmCGM1), expressed in MHV-susceptible mouse strains, and mmCGM2, expressed in SJL/J mice, which are resistant to MHV. We here report the cloning and characterization of a new Bgp-related gene designated Bgp2. The Bgp2 cDNA allowed the prediction of a 271-amino-acid glycoprotein with two immunoglobulin domains, a transmembrane, and a putative cytoplasmic tail. There is considerable divergence in the amino acid sequences of the N-terminal domains of the proteins coded by the Bgp1 gene from that of the Bgp2-encoded protein. RNase protection assays and RNA PCR showed that Bgp2 was expressed in BALB/c kidney, colon, and brain tissue, in SJL/J colon and liver tissue, in BALB/c and CD1 spleen tissue, in C3H macrophages, and in mouse rectal carcinoma CMT-93 cells. When Bgp2-transfected hamster cells were challenged with MHV-A59, MHV-JHM, or MHV-3, the Bgp2-encoded protein served as a functional MHV receptor, although with a lower efficiency than that of the MHVR glycoprotein. The Bgp2-mediated virus infection could not be inhibited by monoclonal antibody CC1 that is specific for the N-terminal domain of MHVR. Although CMT-93 cells express both MHVR and Bgp2, infection with the three strains of MHV was blocked by pretreatment with monoclonal antibody CC1, suggesting that MHVR was the only functional receptor in these cells. Thus, a novel murine Bgp gene has been identified that can be coexpressed in inbred mice with the Bgp1 glycoproteins and that can serve as a receptor for MHV strains when expressed in transfected hamster cells.


title: Genotypes of canine distemper virus determined by analysis of the hemagglutinin genes of recent isolates from dogs in Japan.

text: Canine distemper of domestic dogs is caused by canine distemper virus (CDV), a member of the morbilliviruses. It has been a highly contagious disease of great veterinary importance for centuries, but for the last several decades it has been controlled satisfactorily by modified live vaccines. In the 1990s, however, it was described that CDV strains genetically different from vaccine strains may have caused the disease in vaccinated dogs. The highest antigenic variation is found in the H protein. Therefore, in the present study, hemagglutinin (H) genes obtained from current vaccines and field isolates and amplified directly from clinical specimens were genetically analyzed by restriction fragment length polymorphism assay and sequencing. Phylogenetic analysis of the H-gene amino acid sequences revealed that at least two CDV genotypes are circulating among dogs in Japan; one is a genotype to which almost all Japanese CDV isolates belong and the other has not been previously described. Both are separate and independent from the other lineages or genotypes of vaccine strains, as well as European and U.S. CDV isolates. The results suggest that CDV has also evolved in Japan, and further studies will be needed for an evaluation and possible improvement of the efficacies of current CDV vaccines.


title: Twenty years of clinical human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in Hong Kong.

text: OBJECTIVE To elucidate the development of human immunodeficiency virus (HIV) clinical care and research in Hong Kong. DATA SOURCES Articles on clinical HIV and acquired immunodeficiency syndrome (AIDS) published from 1985 to 2004 were identified through four sources: Red Ribbon Centre, Special Preventive Programme, Secretariat of the Scientific Committee on AIDS, and PubMed search. The first three are operated by the Centre for Health Protection, Department of Health, Hong Kong. STUDY SELECTION Key words for the literature search were 'AIDS', 'HIV', and 'Hong Kong'. DATA EXTRACTION Only papers with original local data were included. DATA SYNTHESIS Sixty papers were identified. The contents were catalogued under seven areas: clinical epidemiology, HIV disease course and presentation, specific complications or organ-based manifestations, immunological evaluation and other monitoring, antiretroviral therapy, HIV/AIDS mortality, and HIV in specific groups. Prevalence of HIV has remained low in Hong Kong but new infections continue to occur together with a significant number of late presenters. Three published AIDS patients' series, up to the first 200 reported cases, identified Pneumocystis carinii pneumonia as the most common AIDS-defining illness in Hong Kong. Penicillium marneffei and Mycobacterium tuberculosis were two important specific infections studied most; uniqueness of the former in patients of South-East Asia was evident. Local studies of Kaposi's sarcoma and HIV-associated lymphoma have also been reported. Research on CD4 counts has revealed that it is lower in healthy and HIV-infected Chinese than their western counterparts. Children, pregnant women, and haemophiliac patients infected with HIV are among the specific groups of patients studied. Survival of patients with advanced disease has greatly improved over the years, particularly after the advent of highly active antiretroviral therapy. CONCLUSION The clinical presentation and outcome of HIV/AIDS patients in Hong Kong are a mixture of those of western and developing countries. Research on clinical HIV/AIDS in Hong Kong is not only beneficial to the planning of patient care, but also enables the formulation of treatment guidelines and provides a reference for other countries.


title: Recombinant protein-based enzyme-linked immunosorbent assay and immunochromatographic tests for detection of immunoglobulin G antibodies to severe acute respiratory syndrome (SARS) coronavirus in SARS patients.

text: An enzyme-linked immunosorbent assay (ELISA) and a rapid immunochromatographic test for detection of immunoglobulin G (IgG) antibodies in severe acute respiratory syndrome (SARS) patients were developed by utilizing the well-characterized recombinant proteins Gst-N and Gst-U274. The ELISA detected IgG antibodies to SARS-CoV in all 74 convalescent-phase samples from SARS patients while weakly cross-reacting to only 1 of the 210 control sera from healthy donors. This finding thus led to a kit sensitivity, specificity, and accuracy of 100, 99.5, and 99.6%, respectively. The test thus provided a positive predictive value (PPV) of 98.7% and a negative predictive value (NPV) of 100%. In addition, the ELISA gave a positive delta of 5.4 and a negative delta of 3.6, indicating an excellent differentiation between positives and negatives. The same recombinant proteins were also applied to a newly developed platform for the development of a 15-min rapid test. The resulting rapid test has an excellent agreement of 99.6%, with a kappa value of 1.00, with the ELISA. Again, this rapid test was able to detect 100% of the samples tested (n = 42) while maintaining a specificity of 99.0% (n = 210). The PPV and NPV for the rapid test thus reached 95.3 and 100%, respectively.


Beta-lactamase production by Campylobacter jejuni.


title: A novel method for protein secondary structure prediction using dual-layer SVM and profiles.

text: A high-performance method was developed for protein secondary structure prediction based on the dual-layer support vector machine (SVM) and position-specific scoring matrices (PSSMs). SVM is a new machine learning technology that has been successfully applied in solving problems in the field of bioinformatics. The SVM's performance is usually better than that of traditional machine learning approaches. The performance was further improved by combining PSSM profiles with the SVM analysis. The PSSMs were generated from PSI-BLAST profiles, which contain important evolution information. The final prediction results were generated from the second SVM layer output. On the CB513 data set, the three-state overall per-residue accuracy, Q3, reached 75.2%, while segment overlap (SOV) accuracy increased to 80.0%. On the CB396 data set, the Q3 of our method reached 74.0% and the SOV reached 78.1%. A web server utilizing the method has been constructed and is available at http://www.bioinfo.tsinghua.edu.cn/pmsvm.


title: Survey of the year 2005 commercial optical biosensor literature.

text: We identified 1113 articles (103 reviews, 1010 primary research articles) published in 2005 that describe experiments performed using commercially available optical biosensors. While this number of publications is impressive, we find that the quality of the biosensor work in these articles is often pretty poor. It is a little disappointing that there appears to be only a small set of researchers who know how to properly perform, analyze, and present biosensor data. To help focus the field, we spotlight work published by 10 research groups that exemplify the quality of data one should expect to see from a biosensor experiment. Also, in an effort to raise awareness of the common problems in the biosensor field, we provide side-by-side examples of good and bad data sets from the 2005 literature.


Beware of False-Positive Results with SARS-CoV-2 Antibody Tests.


title: [Studies on IgG antibodies of SARS patients].

text: OBJECTIVE To investigate the significance of detecting specific serum IgG antibodies in clinical diagnosis of SARS as well as affecting factors. METHODS Enzyme-linked immunoassay kit for SARS coronavirus antibodies developed by HuaDa Biological Company was applied to detect specific serum IgG from SARS patients and the production of SARS specific antibodies among patients of different age groups, sex and with or without steroid treatment were statistically compared. RESULTS Out of 121 patients studied, 71.1% were SARS specific IgG positive. Patients younger than 15 years, between 15 to 59 years, older than 59 years had positive rates of 60.0%, 70.2%, and 85.7%, respectively with no statistically significance (P=0.766); patients with or without steroid treatment showed positive rates of 70.6% and 72.4%, respectively (P=0.84); patients exhibiting either severe or light syndromes showed positive rates of 78.1% and 67.4%, respectively (P=0.493); both male and female patients showed the same positive rate of 71.1%. CONCLUSION The sensitivity of the SARS specific IgG kit utilized needs to be further improved. The production of SARS IgG is not notably correlated with sex, age, seriousness of symptoms, and steroid treatment.


title: [Clinical investigation of the first case of severe acute respiratory syndrome in Beijing in 2004].

text: OBJECTIVE To summarize and analyze the clinical manifestation of the first case of severe acute respiratory syndrome (SARS) in Beijing in 2004, and therefore providing clues of differential diagnosis for physicians to diagnose SARS cases in a timely manner and find out its transmission. METHODS The clinical data of an out-hospital-imported SARS case and its clinical features were analyzed. RESULTS (1) The delay in diagnosis of this SARS case was largely associated with unclear epidemiologic history; (2) The SARS patient showed characteristics of typical pneumonia in the early stage. The numbers of peripheral white blood cells and lymphocytes were in the normal range without any specific changes typical of SARS. CONCLUSION It is very important for physicians to be alert to the epidemiological data for an early diagnosis of SARS, and therefore early isolation and initiation of appropriate treatment.


title: [Ultra powered stapling system for general lung surgery].

text: OBJECTIVE Stapling systems can significantly improve lung tissue approximation during open and video-assisted thoracic surgery. We here evaluated an iDrive Ultra powered stapling system for lung resection. MATERIALS AND METHODS The iDrive Ultra powered stapling system( Covidien) is the powered version of the EndoGIA stapling system. It comprises hand-held control unit combined with a loading unit,which is a powered EndoGIA- cartridges, for use in open and minimally invasive thoracic surgery. The mounted control unit has uses as follows:controlling the accurate placement of the cartridge by orientating the tip of the rigid shaft;and controlling the closure of the stapler and the firing. From April to July 2013, the system was used for a consecutive series of 15 patients during thoracic lung surgery. RESULTS There were 6 women and 9 men, with a mean age of 62 years. The following procedures were performed:lobectomies, segmentectomies, and wedge resections. The system was used for stapling lung parenchyma for wedge resection(5 patients), segmentectomy( 2 patients), or fissure division (9 patients). There were no stapling failures and no complications related to use of the staplers. CONCLUSIONS The new powered and handy stapling system is safe and efficient for lung resection.


title: A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia.

text: Certain infections and malignancies in mammals cause the development of a condition known as cachexia in which the animal continues to lose weight, often while consuming an adequate diet. When macrophages are stimulated with an endotoxin, they produce a factor or factors, termed cachectin, that inhibits the activity of fat-producing (lipogenic) enzymes in cultured adipocytes. This effect may reflect one of the physiological bases for cachexia. In the present study, clones of complementary DNA from genes whose expression is increased during the differentiation of adipocytes were used to study the molecular basis of cachectin's actions. In the presence of cachectin, the expression of the corresponding genes was reversibly and specifically inhibited. Furthermore, when mature adipocytes were exposed to cachectin, the messenger RNA's of those genes diminished and rapidly approached the levels present before differentiation.


title: Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome.

text: It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-alpha, IFN-gamma, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.


title: Synergistic inhibition of pseudorabies virus replication by porcine alpha/beta interferon and gamma interferon in vitro.

text: Interferon (IFN) is crucial for initiating the innate immune response and for the generation of the adaptive response. IFN, in most species, comprises IFN-alpha (IFN-alpha), IFN-beta (IFN-beta) and IFN-gamma (IFN-gamma). In this study, we compared the capacity of porcine IFN-alpha, -beta and -gamma, or a combination of them, to protect IBRS-2 cells (porcine kidney cells) from infection with pseudorabies virus (PRV). The results demonstrated that porcine IFN-beta (PoIFN-beta) was the most efficient of the three IFNs in conferring resistance PRV infection; 100 U/mL PoIFN-beta inhibited PRV plaque formation 5.3-fold. Compared with PoIFN-beta, porcine IFN-gamma (PoIFN-gamma) was less capable of inhibiting PRV plaque formation (3.3-fold inhibition). Porcine IFN-alpha (PoIFN-alpha) had the least capability of the three PoIFNs, and inhibited PRV plaque formation only 1.26-fold. The inhibitory capacity increased to only 2.3-fold with a treatment of 12,800 U/mL PoIFN-alpha. A combination of PoIFN-gamma and PoIFN-alpha or PoIFN-beta inhibited PRV plaque formation 12.8-fold or 100-fold, respectively. Treatment of IBRS-2 cells with PoIFN-alpha/beta and PoIFN-gamma inhibited PRV replication 29- or 146-fold. Additionally, real-time PCR analyses of the PRV immediate early (IE) gene revealed that IE mRNA expression was profoundly decreased in cells stimulated with PoIFN-alpha/beta and PoIFN-gamma (23.8-133.0-fold) compared with vehicle-treated cells. All the findings indicate that PoIFN-gamma acts synergistically with other PoIFNs (PoIFN-alpha and -beta) to potently inhibit PRV replication in vitro.


TZDs and diabetes: testing the waters.


title: [Surveillance strategy for viral zoonotic diseases].

text: Public health surveillance is the ongoing systematic collection, analysis, interpretation, and dissemination of health data. In fact, public health surveillance has been defined quite succinctly as "information for action". Recently, many outbreaks of virus zoonoses are reported in the world, which include West Nile virus disease, avian influenza and severe acute respiratory syndrome (SARS). Public health surveillance is a powerful tool for prevention. However establishing of public health surveillance systems are very difficult for random sampling, sample size and cost. The surveillance of Japanese encephalitis virus activity has been effectively conducted by using seroprevalence of pigs for more than 20 years in Japan. Polio acute flaccid paralysis (AFP) surveillance has been also effectively conducted, although polio cases are decreasing in the world. It is important to understand the character of disease for constructing effective public surveillance systems.


title: Thermal inactivation studies of a coronavirus, transmissible gastroenteritis virus.

text: The thermolability of transmissible gastroenteritis virus (TGEV) was studied between 31 and 55 degrees C using two different strains. The loss of infectivity followed first order kinetics except at the highest temperature. The values of the thermodynamic parameters indicated that the mechanisms involved above and below 45 degrees C are clearly distinct. The rates of inactivation were greater at alkaline than at neutral pH, yet the name of the reaction appeared unchanged. Using four independent stocks of mutagenized virus, we failed to select thermal-resistant mutants by survivor selection at 38 degrees C. In contrast, thermal-resistant mutants were consistently obtained at 54 degrees C. However, the latter did not show any increased stability at 38 degrees C, confirming the fact that a different inactivation process takes place at high and at physiological temperatures.


title: Transmissible gastroenteritis coronavirus, but not the related porcine respiratory coronavirus, has a sialic acid (N-glycolylneuraminic acid) binding activity.

text: The hemagglutinating activity of transmissible gastroenteritis virus (TGEV), an enteric porcine coronavirus, was analyzed and found to be dependent on the presence of alpha-2,3-linked sialic acid on the erythrocyte surface. N-Glycolylneuraminic acid was recognized more efficiently by TGEV than was N-acetylneuraminic acid. For an efficient hemagglutination reaction the virions had to be treated with sialidase. This result suggests that the sialic acid binding site is blocked by virus-associated competitive inhibitors. Porcine respiratory coronavirus (PRCV), which is serologically related to TGEV but not enteropathogenic, was found to be unable to agglutinate erythrocytes. Incubation with sialidase did not induce a hemagglutinating activity of PRCV, indicating that the lack of this activity is an intrinsic property of the virus and not due to the presence of competitive inhibitors. Only monoclonal antibodies to an antigenic site that is absent from the S protein of PRCV were able to prevent TGEV from agglutinating erythrocytes. The epitope recognized by these antibodies is located within a stretch of 224 amino acids that is missing in the S protein of PRCV. Our results indicate that the sialic acid binding activity is also located in that portion of the S protein. The presence of a hemagglutinating activity in TGEV and its absence in PRCV open the possibility that the sialic acid binding activity contributes to the enterotropism of TGEV.


docid: ycsrwdzq

title: Active Telephonic Follow-up During COVID-19 Lockdown: Initial Experience.


Surveillance of viral pathogens in Australia: respiratory syncytial virus.


title: The cell biology of coronavirus infection.

text: The ability to obtain entire volume data on infected cells will allow us to define much more accurately the interactions of viral proteins with host cell structures such as ER, Golgi, and cytoskeletal elements. In addition, the demonstrated ability to express viral proteins fused to fluorescent markers in in live cells will allow us to follow specific proteins or complexes during the course of infection and to determine if exogenously expressed proteins are able to target to sites of active viral replication. This in turn will allow new approaches to the study of viral and cellular protein-protein interactions, as methods to study the biology and pathogenesis of MHV infection at a cellular level. Finally, the approaches described here will allow us to define protein complementation of defective viruses at a cellular level, rather than being dependent on population measurements of RNA, protein, or progeny virus. By combining these approaches with available biochemical and molecular biological approaches and the emerging reverse genetic and recombinant genetic approaches, rapid progress in understanding the details of coronavirus-cell interactions should be possible.


CD8 T cell mediated immunity to neurotropic MHV infection.


title: Quality of life assessment in heart failure interventions: a 10-year (1996-2005) review.

text: The increasing prevalence and poor prognosis associated with heart failure have prompted research to focus on improving quality of life (QoL) for heart failure patients. Research from 1996-2005 was systematically reviewed to identify randomized controlled trials that assessed QoL in heart failure. In 120 studies, 44 were medication trials; 19 surgical/procedural interventions; and 57 patient care/service delivery interventions. Studies were summarized in terms of aim, population, QoL measures used and QoL findings. Studies used 47 different measures of QoL-generic, health-related, condition-specific, domain-specific and utility measures. Most used a single QoL measure. In 87%, a condition specific QoL measure was used, with the Minnesota Living with Heart Failure Questionnaire being the favoured assessment tool. The range of QoL measures in use poses challenges for development of cumulative knowledge. Although comparability across studies is important, this must be informed by the responsiveness of the instrument selected. As carried out in other cardiac groups, comparative evaluations of instrument responsiveness are needed in heart failure.


title: Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong.

text: OBJECTIVE To report the clinical, laboratory, and radiologic features of children with severe acute respiratory syndrome (SARS) and to examine the difference between the younger and older age groups. DESIGN Retrospective descriptive cohort study. SETTING A regional hospital in Hong Kong. PATIENTS Children younger than 18 yrs with SARS. RESULTS Twenty-one children were included, with a mean age of 10.7 +/- 5.1 yrs. Children with SARS presented with fever, nonproductive cough, malaise, chills, headache, myalgia, and loss of appetite. Examination of the chest showed minimal auscultatory findings. Common laboratory findings included lymphopenia, thrombocytopenia, and mild elevations of activated partial thromboplastin time, alanine transaminase, lactic dehydrogenase, and creatine phosphokinase. Bacteriologic and virologic studies were all negative for common pathogens. Unilateral focal opacity was the commonest finding in chest radiography. High-resolution computerized tomography of the thorax was an early diagnostic tool if the chest radiograph was negative. The clinical course was less severe in comparison with adult patients. However, adolescents (age, > or =12 yrs) resembled adults in their clinical features. When compared with the younger age group, the adolescents had significantly higher temperatures, more constitutional upset, and a greater need for steroid treatment. Children younger than 12 yrs seemed less ill but had more coughing. On the whole, the outcome was favorable. CONCLUSION Severe acute respiratory syndrome affects children, but the course is less severe. Nevertheless, the disease could have a significant psychosocial impact on children because of the potential seriousness of the disease in their adult family members.


[Immunogenicity].


title: Lymphocyte blast transformation responses and restriction fragment length analysis in the cheetah.

text: An extensive genetic and physiological analysis of the cheetah by O'Brien et al. (1983; 1985; 1987) indicated that the cheetah showed monomorphism at the major histocompatability complex. This led O'Brien (1985) to propose that the cheetah suffered from an immunodeficiency and was highly susceptible to diseases. It was therefore decided to investigate cell-mediated and humoral immune responses and to apply the limited restriction fragment length analysis (using Pst 1 and Bam H1 enzymes) of the cheetah MHC I and MHC II genes. Antibody responses to antigens (feline viruses), as well as mitogen-induced lymphocyte blast transformation responses, were shown to be intact and comparable with that of the domestic cat, indicating a competent immune system in the cheetah. It was also suggested by the results that some polymorphism does exist in the MHC class II genes, but possibly not in the MHC class I genes.


title: Streptococcus pneumoniae and Mycoplasma pneumoniae coinfection in community acquired pneumonia.

text: The characteristics of nine children with community acquired pneumonia with evidence of Streptococcus pneumoniae and Mycoplasma pneumoniae coinfection are described.


Large Right Atrial Vegetation in a Patient with Tunnelled Dialysis Catheter-Related Staphylococcal Sepsis: Remove the catheter if not in use.


title: Immunity against mucosal pathogens.

text: Immunity against mucosal pathogens-Editor: Michael Vajdy This book highlights the importance of the close interactions of the mucosal immune system with the systemic immune system and the breadth of pathogens and the diversity of pathogenesis associated with infections at mucosal surfaces. The pathogens detailed in the book epitomize the challenges that confront mucosal immunologists and infectious disease researchers. The reader will gain significant insights into these challenges and approaches that researchers attempting to understand mucosal immunology and host-bacterial interactions take to develop effective therapeutic and prophylactic approaches to infection.


title: Epidemiologic survey of diarrhea in foals.

text: Epidemiologic and etiologic data about diarrhea in foals were collected under a planned prospective recording and monitoring study. The survey and monitoring procedures included a survey to obtain an overview of current horse management practices on participating farms, a daily health record survey to obtain information on mares and their foals, and collection of feces from 19 of 144 diarrheic foals and 10 age-matched nondiarrheic foals for electron microscopy, ELISA for rotavirus, and bacteriologic culture. Coronavirus was detected in the feces of diarrheic as well as clinically normal foals. Rotavirus was detected in the feces of diarrheic foals only. With regard to agents found in the feces, there was no significant (P less than 0.05) difference between diarrheic and nondiarrheic foals. Half of the 297 foals on which data were available developed diarrhea. Most foals that developed diarrhea lacked other clinical manifestations of disease. Basic cleanliness at foaling was associated with a lower percentage of foals developing diarrhea. Prophylactic use of antibiotics and vitamins in newborn foals was associated with a higher percentage of foals developing diarrhea. A higher percentage of foals born to visiting mares developed diarrhea, compared with foals born to resident mares.


title: Pharmacotherapy, vaccines and malaria advice for HIV-infected travellers.

text: Since the introduction of effective antiretroviral therapy (ART), HIV-infected individuals are travelling more frequently and international travel has become much safer. Specific concerns include the safety of ART during travel, drug adherence and interaction considerations, and effects of immunosuppression. This review describes potentially important infections, vaccine effectiveness, safety and special approaches for their use, and HIV-related issues regarding predeparture counselling. With advanced immunosuppression (CD4+ T-cell count < 200/microl or < 14%), the immunogenicity of several vaccines is reduced, complications could occur after live attenuated vaccines and certain infections acquired during travel may be more frequent or severe. Challenges include the best options for malaria chemoprophylaxis, standby treatment and medical follow-up of the increasing number of HIV-infected long-term travellers.


title: Simple triage scoring system predicting death and the need for critical care resources for use during epidemics.

text: OBJECTIVES In the event of pandemic influenza, the number of critically ill victims will likely overwhelm critical care capacity. To date, no standardized method for allocating scarce resources when the number of patients in need far exceeds capacity exists. We sought to derive and validate such a triage scheme. DESIGN : Retrospective analysis of prospectively collected data. SETTING Emergency departments of two urban tertiary care hospitals. PATIENTS Three separate cohorts of emergency department patients with suspected infection, comprising a total of 5,133 patients. INTERVENTIONS None. MEASUREMENTS A triage decision rule for use in an epidemic was developed using only those vital signs and patient characteristics that were readily available at initial presentation to the emergency department. The triage schema was derived from a cohort at center 1, validated on a second cohort from center 1, and then validated on a third cohort of patients from center 2. The primary outcome for the analysis was in-hospital mortality. Secondary outcomes were intensive care unit admission and use of mechanical ventilation. MAIN RESULTS Multiple logistic regression demonstrated the following as independent predictors of death: a) age of >65 yrs, b) altered mental status, c) respiratory rate of >30 breaths/min, d) low oxygen saturation, and e) shock index of >1 (heart rate > blood pressure). This model had an area under the receiver operating characteristic curve of 0.80 in the derivation set and 0.74 and 0.76 in the validation sets. When converted to a simple rule assigning 1 point per covariate, the discrimination of the model remained essentially unchanged. The model was equally effective at predicting need for intensive care unit admission and mechanical ventilation. CONCLUSIONS If, as expected, patient demand far exceeds the capability to provide critical care services in an epidemic, a fair and just system to allocate limited resources will be essential. The triage rule we have developed can serve as an initial guide for such a process.


title: [Physiological function of the gastrointestinal tract and pathophysiological changes in neonatal diarrhea of calves].

text: Firstly, the basic principles of absorption and secretion in the intestine of healthy animals are described. The etiology and the pathophysiologic mechanisms of neonatal diarrhea in the calf due to E. coli and rota-/coronavirus are discussed. Enterotoxins of E. coli stimulate primarily the secretion of chloride (and thereby water) in the small intestine without damaging the intestinal mucosa. The sodium-dependent transport systems for the absorption of glucose and amino acids remain intact. In contrast, infections with rota- or coronavirus lead primarily to a disturbance of absorption processes in the intestine due to villous atrophy. Crypt cells are indirectly affected by inflammation mediators. Intestinal motility is inhibited during most diarrheic episodes; the application of para-sympatholytics in therefore not favourable.


title: Age, aerobic fitness, and cerebral perfusion during exercise: role of carbon dioxide.

text: Middle cerebral artery mean velocity (MCAvmean) is attenuated with increasing age both at rest and during exercise. The aim of this study was to determine the influence of the age-dependent reduction in arterial Pco2 (PaCO2) and physical fitness herein. We administered supplemental CO2 (CO2 trial) or no additional gas (control trial) to the inspired air in a blinded and randomized manner, and assessed middle cerebral artery mean flow velocity during graded exercise in 1) 21 young [Y; age 24 ± 3 yr (±SD)] volunteers of whom 11 were trained (YT) and 10 considered untrained (YUT), and 2) 17 old (O; 66 ± 4 yr) volunteers of whom 8 and 9 were considered trained (OT) and untrained (OUT), respectively. A resting hypercapnic reactivity test was also performed. MCAvmean and PaCO2 were lower in O [44.9 ± 3.1 cm/s and 30 ± 1 mmHg (±SE)] compared with Y (59.3 ± 2.3 cm/s and 34 ± 1 mmHg, P < 0.01) at rest, independent of aerobic fitness level. The age-related decreases in MCAvmean and PaCO2 persisted during exercise. Supplemental CO2 reduced the age-associated decline in MCAvmean by 50%, suggesting that PaCO2 is a major component in the decline. On the other hand, relative hypercapnic reactivity was neither influenced by age (P = 0.46) nor aerobic fitness (P = 0.36). Although supplemental CO2 attenuated exercise-induced reduction in cerebral oxygenation (near-infrared spectroscopy), this did not influence exercise performance. In conclusion, PaCO2 contributes to the age-associated decline in MCAvmean at rest and during exercise; however exercise capacity did not diminish this age effect.


title: Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases.

text: OBJECTIVE To determine the impact of respiratory syncytial virus (RSV) infection on healthcare resource use and costs in the US from the third-party payer perspective. DESIGN The study retrospectively analysed cross-sectional medical encounter data from three federally funded databases that comprise nationally representative samples of hospital inpatient stays, physician office visits and visits to hospital outpatient departments and emergency rooms. METHODS Identification of RSV infection-related medical encounters was based on the occurrence of RSV-specific International Classification of Diseases (9th Edition)-Clinical Modification diagnosis codes (079.6, 466.11, 480.1) as principal discharge diagnoses or the assumption that 10-15% of all otitis media visits were due to RSV infection. Outpatient drug costs were estimated based on average wholesale price, and physician fees and test/procedure costs were estimated based on prevailing national fees. Inpatient costs were estimated from total billed charges using a cost-to-charge ratio of 0.53. RESULTS In 2000, nearly 98% of RSV infection-related hospitalisations occurred in children <5 years old. There were approximately 86,000 hospitalisations, 1.7 million office visits, 402 000 emergency room visits and 236,000 hospital outpatient visits for children <5 years old that were attributable to RSV infection. Total annual direct medical costs for all RSV infection-related hospitalisations ($US394 million) and other medical encounters ($US258 million) for children <5 years old were estimated at $US652 million in 2000. Otitis media was a major cost driver for physician visits. RSV infection-related hospitalisations increased from 1993 to 2000, but average costs per hospitalisation were relatively stable. CONCLUSION Treatment of RSV infection-related illness represents a significant healthcare burden in the US. The economic impact of ambulatory care for RSV infection-related illness could be as important as that for RSV infection-related hospitalisation.


title: Counter-COVID- 19 pandemic strategy in the Maghreb Central. Qualitative study of the perceptions of health professionals.

text: CONTEXT The Maghreb Central, like all the countries of the world, was strongly mobilized (governments, ministries of health, population, civil society) in the response against COVID-19, immediately after the registration of the first cases on its territory (end of February, beginning of March) and according to pre-established control strategies. OBJECTIVES Describe the perceptions of health professionals in the Central Maghreb (Tunisia, Algeria and Morocco) as to the Strengths/Opportunities and Weaknesses/Threats of the national response plans against COVID-19, during the first weeks of their execution, and report their proposals for optimizing the performance of control strategies. METHODS This is a qualitative study of the perceptions of health professionals in the Maghreb Central regarding their experience of the first six weeks of fighting the COVID-19 pandemic. The data was collected using the "Delphi" technique in one turn, based on an electronic form such as "Google Form", developed according to SWOT analysis. The respondents' verbatim was grouped into homogeneous groups of items, the occurrence of which was subsequently measured. RESULTS A total of 382 health professionals from the Maghreb Central participated in this study, with a median age of 37 years and a median professional tenure of 10 years. The major force of the Maghreb response strategies, the most shared by the respondents, was the performance of the human resources mobilized (doctors, biologists, nurses, etc.) who succeeded in quickly learning from the international epidemiological expertise accumulated in Asia and in Europe. The fight against COVID-19 in the Central Maghreb was confronted with the general and chronic fragility of the national health systems and the low support of the general population for the recommendations of the steering committees of response, threatening the capacity of the Maghreb to confront new epidemics. CONCLUSION The success of the national response plans against COVID-19 and of possible epidemics or pandemics in the Central Maghreb, is strongly attributed to the commitment of health professionals and to community participation, necessitating the launch of assistant motivation programs. and development of health personnel and mobilization and loyalty of civil society.


title: The severe acute respiratory syndrome coronavirus 3a protein up-regulates expression of fibrinogen in lung epithelial cells.

text: Here we analyzed the gene expression profile of cells that stably express the severe acute respiratory syndrome coronavirus (SARS-CoV) 3a protein to determine its effects on host functions. A lung epithelial cell-line, A549, was chosen for this study because the lung is the primary organ infected by SARS-CoV and fatalities resulted mainly from pulmonary complications. Our results showed that the expression of 3a up-regulates the mRNA levels of all three subunits, Aalpha, Bbeta, and gamma, of fibrinogen. Consequently, the intracellular levels as well as the secretion of fibrinogen were increased. We also observed increased fibrinogen levels in SARS-CoV-infected Vero E6 cells.


title: Tuberculosis in a SARS outbreak.

text: Preoccupied with the diagnosis of SARS (severe acute respiratory syndrome) in a SARS outbreak, doctors tend to overlook other endemic diseases, such as tuberculosis. Incorrectly labeling a patient as SARS may result in serious consequences. Single isolation being not always possible, the patient may have to be isolated with a group of SARS patients. The following article reports how a young girl suffering from pulmonary tuberculosis was erroneously diagnosed as SARS in an outbreak. Isolated with other SARS patients, she was infected with the virus. The treatment of SARS and tuberculosis resulted in liver dysfunction. Fortunately, the patient recovered uneventfully. The importance of keeping an open mind in an outbreak is highlighted.


title: Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections.

text: Viral infection may induce the expression of nitric oxide (NO) synthase, resulting in increased NO formation that has an antiviral effect. NO may be produced by various cells of the upper and lower respiratory tract, and may be detected in the exhaled air. We have studied the levels of exhaled NO in 18 normal subjects during symptomatic upper respiratory tract infections and during recovery 3 weeks later. Exhaled NO was measured using a modified chemiluminescence analyser. At the time of symptoms of upper respiratory tract infection, the peak exhaled NO values were 315 +/- 57 ppb (mean +/- SEM) and decreased to 87 +/- 9 ppb during recovery. Recovery values of exhaled NO were similar to those reported in age-matched normal control subjects (88 +/- 3 ppb, n = 72). These findings suggest that symptomatic upper respiratory tract infections markedly increase the concentration of NO in exhaled air. This may reflect the induction of nitric oxide synthase (NOS) in upper and lower respiratory tract, and may be relevant to viral exacerbations of asthma.


title: [Evaluating healthcare workers' infection control practice in a Lima metropolitan hospital during the influenza A(H1N1) epidemic].

text: OBJECTIVE Determining healthcare workers' level of compliance with infection control practices in a Lima hospital during the influenza A(H1N1) epidemic. METHODS A cross-sectional observational study was made of 165 healthcare workers who provided inpatient care in risk areas like emergency services, emergency, intensive care and hospitalisation. The sample size was calculated using EpiInfo software (version 2000) and was based on simple systematic sampling. An ad hoc format validated by experts' judgement was used. RESULTS 23.6 % (39/165) of the respondents washed their hands before and after contact with patients, 72.7 % (96/132) wore gloves for healthcare when so indicated, 61.0 % (64/105) washed their hands after removing gloves, while 58.0 % (76/131) of those who had contact with contaminated material did so after such contact. Only 14.5 % (24/165) of workers engaged in good practice. CONCLUSIONS The percentage of healthcare workers' engaging in infection control practice in the study hospital during the 2009 influenza A(H1N1) epidemic was low.


Quantitative studies of transformation by chemical carcinogens and ultraviolet radiation using a subclone of BHK21 clone 13 Syrian hamster cells.


[Discussion on preceding papers].


title: Application of bioinformatics in search for cleavable peptides of SARS-CoV M(pro) and chemical modification of octapeptides.

text: According to the "distorted key" theory as elaborated in a review article years ago (Chou, K.C.: Analytical Biochemistry, 1996, 233, 1-14), the knowledge of the cleavable peptides by SARS-CoV M(pro) (severe acute respiratory syndrome coronavirus main proteinase) can provide very useful insights on developing drugs against SARS. In view of this, the softwares, ZCURVE_CoV 1.0 and ZCURVE_CoV 2.0 (http://tubic.tju.edu.cn/sars/), developed recently for SARS-Coronavirus are used to analyze the 36 complete SARS-Coronavirus RNA sequences in the gene bank NCBI (http://www.ncbi.nlm.nih.gov/) from different sources for protein coding genes, and to search for the cleavage sites of SARS-CoV M(pro) in polyproteins pp1a and pp1ab. A total of 396 cleavage points are found in the 36 SARS-Coronavirus and 11 cleavable octapeptides abstracted from the 396 cleavage sites. The statistical distributions of amino acids for the cleavable octapeptides at the subsites R4, R3, R2, R1, R1', R2', R3' and R4' are calculated. The cleavage-specific positions are on R2, R1 and R1', and the positions R3 and R4 are featured by some certain specificity for SARS-CoV M(pro). The structural characters of amino acid residues around the cleavage-specific positions are discussed. Two most promising octapeptides, i.e., NH(2)-ATLQ downward arrowAIAS-COOH and NH(2)-ATLQ downward arrowAENV-COOH, are selected to be the candidates for chemical modification, converting into the inhibitors of SARS-CoV M(pro). A possible strategy to convert a cleavable octapeptide by SARS enzyme into a drug candidate against SARS is elucidated.


title: Self-gripping Covidien™ ProGrip™ mesh versus polypropylene mesh in open inguinal hernia repair: multicenter short term results.

text: The purpose of this study was to compare clinical outcomes following sutureless ProGrip™ mesh repair to traditional Lichtenstein repair with polypropylene mesh secured with sutures. Data were collected prospectively and were analyzed for 57 male and 3 female patients with 60 inguinal hernias. All patients included underwent open surgical repair for inguinal hernia with polypropylene mesh or ProGrip mesh. In our two centres study sixty patients were operated; 30 were treated with Lichtenstein repair with polypropylene mesh (L group) and 30 with ProGrip mesh (P group) with or without fixation. The primary parameter measured was intensity of postoperative pain using visual analogue scale (VAS); other outcomes included assessment of early and late complication. VAS was assessed in 7 days and 4 months of the postoperative period. Our results show that VAS scored at the 7th postoperative day was 1.5 for the ProGrip mesh versus 4.4 in Lichtenstein repair group. The difference between groups was statistically significant (P=0.001). Surgery duration was significantly shorter in the P group (24.9 vs. 58.3 min; P=0.001). No recurrence was observed at 3 months in both groups. The 3-months follow-up has shown that time necessary to return to daily routine activity was significantly lower in the P group during the (P=0.001). Surgery duration, early and late postoperative, pain and return to daily routine activity rates were significantly reduced with self-gripping ProGrip mesh compared to Lichtenstein repair with polypropylene mesh.


title: Adverse effects of feline IL-12 during DNA vaccination against feline infectious peritonitis virus.

text: Cell-mediated immunity is thought to play a decisive role in protecting cats against feline infectious peritonitis (FIP), a progressive and lethal coronavirus disease. In view of the potential of DNA vaccines to induce cell-mediated responses, their efficacy to induce protective immunity in cats was evaluated. The membrane (M) and nucleocapsid (N) proteins were chosen as antigens, because antibodies to the spike (S) protein of FIP virus (FIPV) are known to precipitate pathogenesis. However, vaccination by repeated injections of plasmids encoding these proteins did not protect kittens against challenge infection with FIPV. Also, a prime-boost protocol failed to afford protection, with priming using plasmid DNA and boosting using recombinant vaccinia viruses expressing the same coronavirus proteins. Because of the role of IL-12 in initiating cell-mediated immunity, the effects of co-delivery of plasmids encoding the feline cytokine were studied. Again, IL-12 did not meet expectations - on the contrary, it enhanced susceptibility to FIPV challenge. This study shows that DNA vaccination failed to protect cats against FIP and that IL-12 may yield adverse effects when used as a cytokine adjuvant.


title: Virtual screening for SARS-CoV protease based on KZ7088 pharmacophore points.

text: Pharmacophore modeling can provide valuable insight into ligand-receptor interactions. It can also be used in 3D (dimensional) database searching for potentially finding biologically active compounds and providing new research ideas and directions for drug-discovery projects. To stimulate the structure-based drug design against SARS (severe acute respiratory syndrome), a pharmacophore search was conducted over 3.6 millions of compounds based on the atomic coordinates of the complex obtained by docking KZ7088 (a derivative of AG7088) to SARS CoV M(pro) (coronavirus main proteinase), as reportedly recently (Chou, K. C.; Wei, D. Q.; Zhong, W. Z. Biochem. Biophys. Res. Commun. 2003, 308, 148-151). It has been found that, of the 3.6 millions of compounds screened, 0.07% are with the score satisfying five of the six pharmacophore points. Moreover, each of the hit compounds has been evaluated for druggability according to 13 metrics based on physical, chemical, and structural properties. Of the 0.07% compounds thus retrieved, 17% have a perfect score of 1.0; while 23% with one druggable rule violation, 13% two violations, and 47% more than two violations. If the criterion for druggability is set at a maximum allowance of two rule violations, we obtain that only about 0.03% of the compounds screened are worthy of further tests by experiments. These findings will significantly narrow down the search scope for potential compounds, saving substantial time and money. Finally, the featured templates derived from the current study will also be very useful for guiding the design and synthesis of effective drugs for SARS therapy.


title: Interferon-induction in mouse spleen cells by the Newcastle disease virus (NDV) HN protein.

text: Newcastle disease virus (NDV) envelope glycoproteins that are expressed at the surface of fixed NDV (Ploufragan strain)-infected chick fibroblasts induce interferon (IFN) in mouse spleen cells. HN protein appears to be involved, since an anti-HN monoclonal antibody (Mab 3115) reduces the IFN production to 6% at most. However, the precise site of the molecule responsible for IFN induction is probably not exactly superimposed on the Mab 3115-epitope, since the NDV (83309 strain)-HN protein, which exhibits a modified Mab 3115-epitope, is also able to induce IFN. These preliminary results require further investigation in order to characterize the IFN herein demonstrated, to establish whether this induction mechanism exists in chicken lymphoid cells and to more accurately define the part of the HN molecule involved.


title: The Decreasing Length of Hospital Stay following Vaginal Hysterectomy: 2011-2012 vs. 1996-1997 vs. 1995-1996.

text: Background/Definition of the Problem: In recent years, postoperative management has changed towards rapid mobilisation, early oral feeding and rapid rehabilitation (known as Fast-Track or Enhanced Recovery Concepts). This study analysed the postoperative length of stay after vaginal hysterectomy in 3 different periods of time. Material and Methods: In the period October 2011 - September 2012, 75 patients underwent vaginal hysterectomies (± adnexectomy); another 114 vaginal or laparoscopic hysterectomies with additional operations (e.g. prolapse surgery and incontinence surgery) and malignancies were not included. The time periods August 1995 - July 1996 (n = 50) and October 1996 - September 1997 (n = 96) served as a comparison. Reducing the length of stay was not an explicit goal. Results: The median postoperative stay was shortened from 7 (5-9) to 5 (3-15) or 3 (0-5) days (p < 0.001). The recovery rate remained unchanged at 2.7 % (n = 2), cf. 2 % (n = 1) and 3.1 % (n = 3). In 40/75 cases (53.3 %), the surgery took place on the day of admission. Conclusion: The length of hospital stay after vaginal hysterectomy has more than halved since 1995/1996 and continues to decline. This development occurred without a shortened stay being an explicit goal of the clinic. The shortened length of stay does not appear to have a negative impact on postoperative complications and recovery rate.


title: Human coronavirus OC43 pneumonia in a pediatric cancer patient with down syndrome and acute lymphoblastic leukemia.

text: In this report, we describe a case of pneumonia due to an infection with human coronaviruses (HCoVs)-OC43 in a pediatric leukemia patient with Down syndrome and febrile neutropenia. Not only the recently discovered HCoVs NL63 or HKU1 but also the prototype strains HCoV-OC43 and HCoV-229E have to be considered as respiratory pathogens in immunocompromised pediatric cancer patients. The routine utilization of polymerase chain reaction-based diagnostic tools would certainly elucidate the etiology of a relevant proportion of "pneumonias of unknown origin" in immunocompromised pediatric patients and would contribute to a better understanding of the role of HCoVs in this setting.


title: Olivopontocerebellar atrophy in two adult cats, sporadic cases or new genetic entity.

text: Two otherwise healthy adult cats were presented with progressive cerebellar signs of different severity. Owners requested euthanasia. Necropsy disclosed whole cerebellum and pontine atrophy, with a severity paralleling the neurologic dysfunction. We used cell type-specific immunolabelings to characterize the lesions. The severity of the cerebellar cortex atrophy followed a general gradient from the midvermis toward the hemispheres and a local gradient from the depth of the folia toward their tip. Along these gradients, Purkinje cells were the first to disappear, followed by basket, Golgi, and stellate cells, and eventually by granule cells. Bergmann glia cells and unipolar brush cells were preserved. Pontine nuclei and the olivary complex were also severely depopulated. Neurons in the cerebellar nuclei, vestibular nuclei, and other cerebellar system-associated structures were preserved, as well as substantia nigra. Olivopontocerebellar atrophy (OPCA) in a domestic animal species was rarely reported. Some features allow tentative linking to either familial or sporadic OPCA of humans. However, the ordered disappearance of all cortical neuronal types has never been described before. Either this entity is cat specific or it might pinpoint the need for increased knowledge about differential gene expression depending on genetic background, i.e., among different species. It also would open prospects about gene product interactions within neurons.


title: Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.

text: BACKGROUND The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. METHODS The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. RESULTS In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. CONCLUSIONS The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.


title: Structural and biochemical investigation of heptad repeat derived peptides of human SARS corona virus (hSARS-CoV) spike protein.

text: hSARS-CoV is the causative agent for SARS infection. Its spike glycoprotein (S) is processed by host furin enzyme to produce S1 and S2 fragments, the latter being crucial for fusion with the host membrane. This takes place via formation of a coiled coil 6-helix bundle involving N and C-terminal heptad repeat domains (HR-N and HR-C) of S2. Several fluorescent and non-fluorescent peptides from these domains were synthesized to examine their interactions by circular dichroism, thermal denaturation, native-page, mass spectrometry and fluorescence spectroscopy studies. Data revealed that HR-C domains (1153-1189), (1153-1172) and (1164-1184) all exhibit potent binding interactions with HR-N(892-931) domain. These peptides may find useful therapeutic applications in SARS intervention.


title: Inhaled modified angiotensin converting enzyme 2 (ACE2) as a decoy to mitigate SARS-CoV-2 infection.

text: COVID-19 is a new zoonotic disease caused by the SARS-CoV-2 virus. Since its emergence in Wuhan City, China, the virus has rapidly spread across the globe causing calamitous health, economic and societal consequences. It causes disproportionately severe disease in the elderly and those with co-morbidities, such as hypertension and diabetes. There is currently no proven treatment for COVID-19 and a safe and effective vaccine is at least a year away. The virus gains access to the respiratory epithelium through cell surface angiotensin converting enzyme 2 (ACE2). The receptor binding domain (RBD) of the virus is unlikely to mutate without loss of pathogenicity and thus represents an attractive target for antiviral treatment. Inhaled modified recombinant human ACE2, may bind SARS-CoV-2 and mitigate lung damage. This decoy strategy is unlikely to provoke an adverse immune response and may reduce morbidity and mortality in high-risk groups.


Abstract book.


title: The pathology of neonatal enteritis in calves with observations on E. coli, rotavirus and Cryptosporidium.

text: The mucosa of the small intestine of neonatal calves responds in a similar way to a variety of infectious agents. However, samples should be removed under general anaesthesia to avoid post-mortem artefacts. These include the separation of epithelium from the villous lamina propria and denudation of villous tips within a few minutes of death, and occur more rapidly in challenged animals. Pathological changes consist of blunting and fusion of the villi with a reduction of the columnar epithelium to cuboidal and occasionally squamous epithelium. A surface inflammatory exudate may be present, especially within 24 hours of challenge with enteropathogenic E. coli. Examination of several sites from the small intestine indicates a variable distribution for enteropathogens. Rotavirus is seen by immunofluorescence microscopy in epithelial cells principally in the proximal half of the small intestine, although they may occasionally be found in the distal half. By contrast, E. coli organisms adhere to enterocytes in the distal half of the small intestine. Cryptosporidia inhabit the brush border of the enterocytes enclosed within host cell microvillous membranes, principally in the distal half of the small intestine. Examination of the small intestine of neonatal calves for pathological changes and the presence and distribution of infectious agents complements bacteriological, virological and immunological techniques in the diagnosis of neonatal enteritis.


Increasing the global exchange of evidence-based research.


title: Infant mouse model of E. coli diarrhoea: clinical protection induced by vaccination of the mothers.

text: Protection of infant mice against experimental E. coli B41 diarrhoea by immunization of the mothers with homologous E. coli strain was studied. The influence of the number, dose, route and moment of vaccination(s) on protection, measured by the reduced mortality rate of infant mice during the 15 days following oral challenge, was tested. The highest dose of vaccine, namely 10(8) formalin-killed E. coli by parenteral routes or 3 X 10(9) live E. coli by peroral (p.o.) route resulted in the best effect, whatever the immunization procedure used. A single vaccination of the mothers mainly delayed death without marked reduction of the mortality rate. Subcutaneous (s.c.) immunization with 10(8) formalin-killed E. coli was nevertheless more efficient than p.o. vaccination with 3 X 10(8) live E. coli. Equal levels of protection were observed when the above s.c. vaccination occurred either 15 days before the onset of gestation or on the 8th day or 15th day. In contrast, the p.o. immunization resulted in no effect when done on the 15th day of gestation. Great improvement in protection was obtained with two vaccinations, when priming occurred 15 days before the onset of gestation and boosting on the 8th day, except with two combined p.o. vaccinations with 3 X 10(8) live E. coli. Both dosages of priming and boosting seemed to matter. Peroral, subcutaneous or intraperitoneal priming with about 10(8) E. coli resulted in nearly equal effects, when boosting occurred subcutaneously with 10(8) killed E. coli. However, i.p. priming probably resulted in some non-specific effect, as shown by the slower clinical evolution of the controls. A tenfold dosage increase in p.o. priming alone led to the best protective effect observed when boosting was done three weeks after priming. The occurrence of s.c. boosting one week later, namely four weeks after priming, markedly improved protection with every route tested, and more particularly with the s.c. one. However, complete protection was never obtained. Protective effect was mostly transmitted after birth by the colostrum and the milk of the immune mothers, as demonstrated by cross-fostering experiments. Using the best immunization procedures, variability of the model was studied, by repeating experiments several times. Clinical evolution of the controls was very similar from one experiment to another, whatever the route and the moment of immunizations. In contrast, vaccinated groups showed variations which increased with time, especially on and after seven days following inoculation. Clinical evolution of individual litters belonging to the same experimental group indicated that each mother did not equally respond to the vaccination.


docid: wuwotxkz

title: [SARS, possible zoonosis in the area of conflict of pathogenic coronaviruses of animals].

text: Severe acute respiratory syndrome (SARS) is an emerging disease, which was first recognized in Guangdong Province, China, in November 2002. In the meantime, SARS has been recognized in patients on all five continents. A novel coronavirus, which is not related to the hitherto known coronaviruses, has been proven to be associated with the disease. Our genomic analyses strongly suggest that the new SARS-coronavirus did not emerge through mutation or recombination and that it has probably been transmitted from a so far not identified animal species to humans. Therefore, it is most likely that SARS virus is a zoonotic agent. A broad body of knowledge originating from research in veterinary medicine indicates that development of vaccines against the SARS-coronavirus may be problematic. The potential danger of such vaccines should not be neglected during the process of vaccine development.


Influenza.


docid: zkzayeak

title: Release of Rice dwarf virus from insect vector cells involves secretory exosomes derived from multivesicular bodies.

text: Plant reoviruses in insect vector cells are sequestered in spherical multivesicular compartments. We demonstrated previously that the plant-infecting reovirus Rice dwarf virus (RDV) exploits multivesicular compartments for the transport and release of viral particles from infected insect vector cells. These multivesicular compartments contain small vesicles and, morphologically, they resemble previously reported endosomal multivesicular bodies (MVBs) exploited by enveloped RNA viruses during budding from the plasma membrane of infected cells. Electron microscopy revealed that, at a late stage of infection, RDV virions are released, together with small vesicles similar to secreted vesicles (exosomes), from infected cells. The incorporation of lysosomes into the multivesicular compartments raised the possibility that functions of host MVBs are required for the efficient release of RDV virions from infected insect vector cells. An actin-myosin transport system has been shown to mediate the transport of these multivesicular compartments. In this addendum, we provide evidence for the proposed model of release of RDV virions from infected insect vector cells that exploits secretory exosomes derived from MVBs.


title: Correct Evaluation of Gastric Wall Thickness May Support a Change in Staplers' Size When Performing Sleeve Gastrectomy.

text: BACKGROUND Leakage from the staple line is the most serious complication encountered after sleeve gastrectomy, occurring in 2.4% of surgeries. The use of inappropriately sized staplers, because of variability in stomach wall thickness, is a major cause of leakage. OBJECTIVES To measure stomach wall thickness across different stomach zones to identify variables correlating with thickness. METHODS The study comprised 100 patients (52 females). Stomach wall thickness was measured immediately after surgery using a digital caliper at the antrum, body, and fundus. Results were correlated with body mass index (BMI), age, gender, and pre-surgical diagnosis of diabetes, hypertension, hyperlipidemia and fatty liver. RESULTS Stomach thickness was found to be 5.1 ± 0.6 mm at the antrum, 4.1 ± 0.6 mm at the body, and 2. 6 ± 0.5 mm at the fundus. No correlation was found between stomach wall thickness and BMI, gender, or co-morbidities. CONCLUSIONS Stomach wall thickness increases gradually from the fundus toward the antrum. Application of the correct staple height during sleeve gastrectomy is important and may, theoretically, prevent leaks. Staplers should be chosen according to the thickness of the tissue.


title: Induction of transmissible gastroenteritis coronavirus-neutralizing antibodies in vitro by virus-specific T helper cell hybridomas.

text: Three transmissible gastroenteritis (TGE) virus-specific T helper (Th) cell hybridomas have been generated from virus-primed BALB/c mice, by fusion with the thymoma BW5147. The hybridomas responded to purified u.v.-inactivated TGE virus with interleukin production and growth inhibition. TGE virus recognition by the hybridomas was restricted by the major histocompatibility complex: only splenocytes from syngeneic or semi-syngeneic mice were able to recognize the antigen. The three hybridomas were Thy 1.2+, but did not express detectable levels of Lyt 1 or Lyt 2 antigens by fluorescent cell sorting analysis. Only one hybridoma (T.1J.B5) expressed the L3T4 marker. These hybridomas had helper activity, as they were able to reconstitute in vitro the synthesis of TGE virus-specific antibodies by Th cell-depleted spleen cells from immune BALB/c mice. The antibodies that they induced specifically neutralized by 10(3)- to 10(4)-fold the infectivity of TGE virus, ruling out the possibility of inhibition of virus replication by interferon. These hybridomas could be very useful for identifying antigenic domains in TGE virus recognized by Th cells, which cooperate with B cells in the synthesis of neutralizing antibodies.


Czech stem-cell work heightens calls for EU ruling.


WHO meeting targets global concerns.


title: Early experience with laparoscopic sleeve gastrectomy as a single-stage bariatric procedure.

text: Laparoscopic sleeve gastrectomy (LSG) as a single-stage restrictive bariatric procedure is becoming increasingly popular, especially in patients who are high risk and/or superobese. Between November 21, 2006, and September 30, 2008, 42 patients underwent LSG at our institution. Average age was 47 +/- 11 years, average body mass index was 54 +/- 10 kg/m2, and 62 per cent were female. Preoperative indications for LSG included contraindication to laparoscopic Roux-en-Y gastric bypass (n = 11), severe coronary artery disease and/or congestive heart failure (n = 3), significant liver disease (n = 3), and patient preference (n = 4). Intraoperative indications for LSG included a foreshortened mesentery with inability to create a gastrojejunostomy (n = 13), extensive adhesions (n = 5), and intraoperative findings concerning for cirrhosis (n = 3). Twelve complications occurred in six patients: laparoscopic to open conversion (n = 1), reoperation (n = 3), nosocomial pneumonia (n = 1), wound infection (n = 1), bleeding (n = 1), pulmonary embolus (n = 1), readmission (n = 3), and superior splenic pole infarction. There was one death resulting from pulmonary embolism that occurred 2 weeks postoperatively. Preliminary excess body weight loss at 3, 6, 9, and 12 months was 29, 32 t, 38, and 30 per cent, respectively, and many patients had improvement or resolution of obesity-related comorbidities. Early review of our experience demonstrates that LSG may be an effective single-stage bariatric procedure. Additional follow up will be necessary to better define its long-term safety and efficacy.


title: [A preliminary investigation on the serological and epidemiological characteristics of severe acute respiratory syndrome in children].

text: OBJECTIVE The severe acute respiratory syndrome (SARS) is a highly contagious infection caused by a newly discovered strain of coronavirus (SARS-CoV). During the outbreak of SARS in the first half of 2003, children appeared to be less susceptible to the SARS coronavirus and pediatric patients presented with a less aggressive clinical course than adult patients did, demonstrating the traits which were rarely observed in other viral contagious disease. The present study aimed to preliminarily examine the presence of serum specific antibodies against severe acute respiratory syndrome (SARS)-associated coronavirus virus (SARS-CoV) in pediatric SARS patients and explore the possibility of subclinical infection in children/adults through close association with SARS cases. METHODS (1) Clinicians and nurses visited families and collected general and epidemiological information about the subjects using a standard questionnaire and took serum specimens. (2) Specific antibodies against SARS-CoV were assayed with two methods, indirect immunofluorescence assay (IFA) for detecting IgG antibodies and enzyme linked immunosorbent assay (ELISA) for mixed antibodies. Serum specimens tested included those from 21 clinically confirmed pediatric SARS cases (aged from 8 months to 14 years, 11 male and 10 female) and their 23 parents who had close contact with the children, 36 adult patients in convalescence stage of SARS, 24 children (aged 1.5 to 14 years) and other 34 adults who had close contact with infected adults. RESULTS (1) The positive rates of specific IgG and mixed antibodies against SARS-CoV were 38% (8/21) and 33% (7/21) in pediatric cases; whereas the rates were 75% (27/36) and 69% (25/36) in adult patients. (2) The proportion of the patients who had close contact to SARS patients was 7/8 among the antibody-positive group vs. 1/13 for the antibody-negative group (P < 0.05). (3) The IgG antibody emerged in one of 24 children, whose mother, a nurse, had suffered from SARS (4%). (4) Among 23 parents of children with SARS, one was positive for IgG and the mixed antibodies, whose grandson and husband suffered from SARS; The IgG antibody and the mixed antibodies were also positive in another adult who had close contact with adult SARS cases (3%). CONCLUSIONS (1) SARS-CoV infection was confirmed by serological methods in 38.1% of clinically diagnosed pediatric SARS cases, which leads to the assumption that correct diagnosis of pediatric SARS requires more accurate and efficient ways, for example, screening for antigen or gene of SARS-CoV. (2) The proportion of the patients who had close contact to SARS patients among antibody-positive cases was higher than that in antibody-negative cases. (3) It is possible that subclinical SARS CoV infection exists in children and adults, although the rate of occurrence is low. The data of the present study did not confirm that SARS had subclinical infection among adults who had close contact to pediatric SARS cases.


title: Totally laparoscopic right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure.

text: BACKGROUND During laparoscopic right hemicolectomy, most surgeons perform an extracorporeal anastomosis. A totally laparoscopic procedure with intracorporeal anastomosis may improve cosmesis because midline- or paraumbilical incisions can be avoided. Here, we investigate the safety of an intracorporeal anastomosis from a technical and oncological perspective. METHODS All patients who underwent right hemicolectomy with intracorporeal anastomosis between 2003-2011 were retrospectively analyzed. Parameters were duration of surgery, intraoperative blood loss, mortality and morbidity. Adequacy of oncologic resections was scored by resectional margins and number of harvested lymph nodes. RESULTS A total of 162 patients were included with a median age of 69 years (IQR60-76). The duration of surgery was 100 minutes (80-120) and intraoperative blood loss was 30 mL (10-100). Hundred-twenty patients (74%) underwent an oncologic resection. Number of harvested lymph nodes was 12 (9-18). RO-resection was achieved in 100%. Four patients died (2.5%). Postoperative complications were: anastomotic leakage (3.1%; n = 5), ileus (4.9%; n = 8), abscesses (2.5% ; n = 4), wound infection (3.1% ; n = 5) and cardiopulmonary complications (10.5% ; n = 17). Duration of oncological follow-up was 2.5 years (1.3-4.6). Local recurrence and overall survival rates at two years were 0.8% and 85.4%, respectively. CONCLUSION Right hemicolectomy with intracorporeal anastomosis is a technically and oncologically safe procedure with acceptable operating time and low mortality.


title: Interferon alpha inducing property of coronavirus particles and pseudoparticles.

text: Previous work in our laboratory have provided evidence that the membrane glycoprotein M of TGEV is centrally involved in efficient induction of alpha interferon (IFN-alpha) synthesis by non-immune peripheral blood mononuclear cells incubated with fixed, TGEV-infected cells or inactivated virions. Here we report recent completion of studies initiated to get a better understanding of the nature of the interferogenic determinant(s). Transfected cells expressing TGEV M together with the minor structural component E (formerly called sM) were found to trigger IFN-alpha synthesis. Co-expression of these two proteins was shown to be necessary and sufficient for assembly and release of pseudoparticles resembling TGEV virions. Purified pseudoparticles exhibited an interferogenic activity close to that of authentic virions. Chimeric recombinant particles expressing BCV M ectodomain also induced IFN. Examination of cell cultures infected by viruses representative of the three Nidovirales genera revealed that the capacity to act as an efficient IFN-alpha inducer is a common feature of viral particles of the coronavirus genus. Altogether these data bring new insights regarding the putative nature of the viral structure involved in IFN-alpha induction.


Human-Animal Health Interactions: The Role of One Health.


title: Autoimmune diabetes and resistance to xenograft transplantation tolerance in NOD mice.

text: Costimulation blockade induces prolonged rat islet and skin xenograft survival in C57BL/6 mice. Nonobese diabetic (NOD) mice, which are used to model human autoimmune diabetes, are resistant to costimulation blockade-induced allograft tolerance. We tested the hypothesis that NOD mice would also be resistant to costimulation blockade-induced rat xenograft tolerance. We report that rat islet xenograft survival is short in spontaneously diabetic NOD mice treated with a tolerizing regimen of donor-specific transfusion and anti-CD154 antibody. Rat islet xenograft survival is only marginally longer in chemically diabetic NOD mice treated with costimulation blockade but is prolonged further in NOD Idd congenic mice bearing C57-derived chromosome 3 loci. Reciprocally, the presence of NOD-derived chromosome 3 loci shortens islet xenograft survival in tolerized C57BL/6 mice. Islet xenograft survival is longer in tolerized NOD.CD4a(-/-) and (NOD x C57BL/6)F1 mice than in NOD mice but still much shorter than in C57BL/6 mice. Skin xenograft survival in (NOD x C57BL/6)F1 mice treated with costimulation blockade is short, suggesting a strong genetic resistance to skin xenograft tolerance induction. We conclude that the resistance of NOD mice to xenograft tolerance induction involves some mechanisms that also participate in the expression of autoimmunity and other mechanisms that are distinct.


title: The Effect of Sterile Acellular Dermal Matrix Use on Complication Rates in Implant-Based Immediate Breast Reconstructions.

text: BACKGROUND The use of acellular dermal matrix (ADM) in implant-based immediate breast reconstruction has been increasing. The current ADMs available for breast reconstruction are offered as aseptic or sterile. No published studies have compared aseptic and sterile ADM in implant-based immediate breast reconstruction. The authors performed a retrospective study to evaluate the outcomes of aseptic versus sterile ADM in implant-based immediate breast reconstruction. METHODS Implant-based immediate breast reconstructions with ADM conducted between April 2013 and January 2016 were included. The patients were divided into 2 groups: the aseptic ADM (AlloDerm) group and the sterile ADM (MegaDerm) group. Archived records were reviewed for demographic data and postoperative complication types and frequencies. The complications included were infection, flap necrosis, capsular contracture, seroma, hematoma, and explantation for any cause. RESULTS Twenty patients were reconstructed with aseptic ADM, and 68 patients with sterile ADM. Rates of infection (15.0% vs. 10.3%), flap necrosis (5.0% vs. 7.4%), capsular contracture (20.0% vs. 14.7%), seroma (10.0% vs. 14.7%), hematoma (0% vs. 1.5%), and explantation (10.0% vs. 8.8%) were not significantly different in the 2 groups. CONCLUSIONS Sterile ADM did not provide better results regarding infectious complications than aseptic ADM in implant-based immediate breast reconstruction.


title: Troponin elevations after non-cardiac, non-vascular surgery are predictive of major adverse cardiac events and mortality: a systematic review and meta-analysis.

text: BACKGROUND Patients undergoing non-cardiac, non-vascular surgery are at risk of major cardiovascular complications. In non-cardiac surgery, troponin elevation has previously been shown to be an independent predictor of major adverse cardiac events and postoperative mortality; however, a majority of studies have focused on vascular surgery patients. The aim of this meta-analysis was to determine whether troponin elevation is a predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery. METHODS A systematic review and meta-analysis was conducted in January 2016 according to the Meta-analysis Of Observational Studies in Epidemiology guidelines. Both interventional and observational studies measuring troponin within the first 4 days after surgery were eligible. A systematic search was performed in PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials. RESULTS Eleven eligible clinical studies (n=2193) were identified. A postoperative troponin elevation was a predictor of 30 day mortality, odds ratio (OR) 3.52 [95% confidence interval (CI) 2.21-5.62; I2=0%], and an independent predictor of 1 yr mortality, adjusted OR 2.53 (95% CI 1.20-5.36; I2=26%). A postoperative troponin elevation was associated with major adverse cardiac events at 30 days, OR 5.92 (95% CI 1.67-20.96; I2=86%), and 1 yr after surgery, adjusted OR 3.00 (95% CI 1.43-6.29; I2=21%). CONCLUSIONS Postoperative myocardial injury is an independent predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery. The meta-analysis provides evidence that supports troponin monitoring as a cardiovascular risk stratification tool.


title: Diagnosis and treatment of sleep related breathing disorders in children: 2007 to 2011.

text: Sleep related breathing disorders (SRBD) have historically been under-recognised and under-treated. Obstructive sleep apnoea (OSA) affects approximately 3% of children. In line with the increased recognition of SRBD there has been an increase in demand for diagnostic services. We determined the awareness of SRBD amongst Irish paediatricians, examined the provision of sleep services to children throughout the country between 2007 and 2011 and audited diagnostic sleep services in a tertiary centre in 2011. Amongst respondents there was an awareness of SRBD but a poor understanding of diagnostic evaluation with 31/46 (67) referring to inappropriate services. There has been a sharp increase in both diagnostic sleep tests (433-1793 [414]) and in the use of non-invasive ventilation (NIV) (31-186 [627]) for treatment of SRBD between 2007 and 2011. Paediatric sleep services are organized in an ad-hoc manner nationally with significant service variation. The use of domiciliary overnight oximetry reduced the requirement for more formal polysomnography by 70%.


title: Contact tracing and disease control.

text: Contact tracing, followed by treatment or isolation, is a key control measure in the battle against infectious diseases. It is an extreme form of locally targeted control, and as such has the potential to be highly efficient when dealing with low numbers of cases. For this reason it is frequently used to combat sexually transmitted diseases and new invading pathogens. Accurate modelling of contact tracing requires explicit information about the disease-transmission pathways from each individual, and hence the network of contacts. Here, pairwise-approximation methods and full stochastic simulations are used to investigate the utility of contact tracing. A simple relationship is found between the efficiency of contact tracing necessary for eradication and the basic reproductive ratio of the disease. This holds for a wide variety of realistic situations including heterogeneous networks containing core-groups or super-spreaders, and asymptomatic individuals. Clustering (transitivity) within the transmission network is found to destroy the relationship, requiring lower efficiency than predicted.


title: Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration.

text: OBJECTIVE Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxia-reoxygenation. METHODS Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR <60 beats/min) or severe hypotension (MAP <15 mmHg). The animals were divided into four groups based on the oxygen (O(2)) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O(2), respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (<15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (>90 min), and E: nine deceased piglets. RESULTS Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO(2) used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events.


title: A two-year longitudinal study on the etiology of acute diarrhea in young children in Northern Italy.

text: During a 24-month period, 561 young children (6 months-2 years of age) hospitalized for acute diarrhea were studied for enteric pathogens. Patients positive for one or more pathogens were 359 (64.0%). Infection with one pathogen was found in 266 (47.4%) patients, whereas multiple infection was detected in 93 (16.6%) patients. Enteropathogens associated with disease were Rotaviruses: 150 (26.7%), Adenoviruses: 99 (17,6%), non-polio Enteroviruses: 48 (8.5%), Coronaviruses: 10 (1.8%), Parvoviruses: 5 (0.9%), Salmonella sp.: 41 (7.3%), Campylobacter fetus: 45 (8.0%), Giardia lamblia: 8 (1.4%), and "enteropathogenic" E. coli: 63 (11.2%) of which 15 (3%) produced heat labile enterotoxin. Seasonal occurrence of enteropathogens is also described.


title: Replication of human respiratory coronavirus strain 229E in human macrophages.

text: Evidence for the replication of human coronavirus strain 229E (HCV 229E) in macrophages is presented. Virus antigen was detected in macrophages by an immunofluorescent technique 24 h after infection and virus particles were observed in the cisternae of the endoplasmic reticulum by electron microscopy. Giant cells were observed by light and scanning electron microscopy, and large multinucleate cells were seen by thin-section electron microscopy, suggesting that HCV 229E can induce syncytial formation in cultured human macrophages. Furthermore, the production of infectious virus by macrophages was demonstrated by an infectious centre assay.


docid: ubtycpvr

title: Outcomes of Nosocomial Viral Respiratory Infections in High-Risk Neonates.

text: BACKGROUND AND OBJECTIVE Neonatal respiratory disease, particularly bronchopulmonary dysplasia, remains one of the leading causes of morbidity and mortality in newborn infants. Recent evidence suggests nosocomially acquired viral respiratory tract infections (VRTIs) are not uncommon in the NICU. The goal of this study was to assess the association between nosocomial VRTIs, neonatal respiratory disease, and the health care related costs. METHODS A matched case-control study was conducted in 2 tertiary NICUs during a 6-year period in Nottingham, United Kingdom. Case subjects were symptomatic neonatal patients with a confirmed real-time polymerase chain reaction diagnosis of a VRTI. Matched controls had never tested positive for a VRTI. Multivariable logistic regression was used to test for associations with key respiratory outcomes. RESULTS There were 7995 admissions during the study period, with 92 case subjects matched to 183 control subjects. Baseline characteristics were similar, with a median gestation of 29 weeks. Rhinovirus was found in 74% of VRTIs. During VRTIs, 51% of infants needed escalation of respiratory support, and case subjects required significantly more respiratory pressure support overall (25 vs 7 days; P < .001). Case subjects spent longer in the hospital (76 vs 41 days; P < .001), twice as many required home oxygen (37%; odds ratio: 3.94 [95% confidence interval: 1.92-8.06]; P < .001), and in-hospital care costs were significantly higher (£49 664 [$71 861] vs £22 155 [$32 057]; P < .001). CONCLUSIONS Nosocomial VRTIs in neonatal patients are associated with significant greater respiratory morbidity and health care costs. Prevention efforts must be explored.


Clinical and biological distinctions between type I and type II acquired angioedema.