title: Community-acquired pneumonia in the post 13-valent pneumococcal conjugate vaccine era.

text: PURPOSE OF REVIEW This review covers the outpatient management of pediatric community-acquired pneumonia (CAP), discussing the changing microbiology of CAP since the introduction of the 13-valent pneumococcal conjugate vaccine in 2010, and providing an overview of national guideline recommendations for diagnostic evaluation and treatment. RECENT FINDINGS Rates of invasive pneumococcal disease and pneumococcal antibiotic resistance have plummeted since widespread 13-valent pneumococcal conjugate vaccine immunization. Viruses remain the most common cause of CAP in young children; children over age 5 years have increased rates of Mycoplasma pneumoniae. A recent national guideline offers recommendations for office-based diagnostic evaluation and treatment of pediatric CAP. SUMMARY This review offers a discussion of the above findings with practical recommendations for the office-based practitioner in the evaluation and treatment of an infant (>3 months) or child with suspected CAP.


title: Nurses' fears and professional obligations concerning possible human-to-human avian flu.

text: This survey aimed to illustrate factors that contribute to nurses' fear when faced with a possible human-to-human avian flu pandemic and their willingness to care for patients with avian flu in Taiwan. The participants were nursing students with a lesser nursing credential who were currently enrolled in a bachelor degree program in a private university in southern Taiwan. Nearly 42% of the nurses did not think that, if there were an outbreak of avian flu, their working hospitals would have sufficient infection control measures and equipment to prevent nosocomial infection in their working environment. About 57% of the nurse participants indicated that they were willing to care for patients infected with avian influenza. Nurses' fear about an unknown infectious disease, such as the H5N1 influenza virus, could easily be heightened to levels above those occurring during the 2003 severe acute respiratory syndrome outbreak in Taiwan.


title: Abdominal ultrasonographic findings associated with feline infectious peritonitis: a retrospective review of 16 cases.

text: The feline infectious peritonitis virus (FIPV) is a mutated form of the feline enteric coronavirus (FeCV) that can present with a variety of clinical signs. The purpose of this retrospective study was to analyze abdominal ultrasonographic findings associated with cats with confirmed FIPV infection. Sixteen cases were included in the study from a review of medical records at two academic institutions; inclusion was based either on necropsy lesions (n=13) or a combination of histopathological, cytological, and clinicopathological findings highly suggestive of FIPV infection (n=3). The liver was judged to be normal in echogenicity in 11 (69%) cats, diffusely hypoechoic in three cats, focally hyperechoic in one cat, and focally hypoechoic in one cat. Five cats had a hypoechoic subcapsular rim in one (n=3) or both (n=2) kidneys. Free fluid was present in the peritoneal cavity in seven cats and in the retroperitoneal space in one cat. Abdominal lymphadenopathy was noted in nine cats. The spleen was normal in echogenicity in 14 cats and was hypoechoic in two. One cat had bilateral orchitis with loss of normal testicular architecture. Although none of these ultrasonographic findings are specific for FIPV infection, a combination of these findings should increase the index of suspicion for FIPV infection when considered along with appropriate clinical signs.


Meeting the survival needs of the world's least healthy people: a proposed model for global health governance.


Caught napping in the time of tropical diseases.


title: Molecular epidemiology of the foot-and-mouth disease virus outbreak in the United Kingdom in 2001.

text: The objective of this study was to quantify the extent to which the genetic diversity of foot-and-mouth disease virus (FMDV) arising over the course of infection of an individual animal becomes fixed, is transmitted to other animals, and thereby accumulates over the course of an outbreak. Complete consensus sequences of 23 genomes (each of 8,200 nucleotides) of FMDV were recovered directly from epithelium tissue acquired from 21 farms infected over a nearly 7-month period during the 2001 FMDV outbreak in the United Kingdom. An analysis of these consensus sequences revealed very few apparently ambiguous sites but clear evidence of 197 nucleotide substitutions at 191 different sites. We estimated the rate of nucleotide substitution to be 2.26 x 10(-5) per site per day (95% confidence interval [CI], 1.75 x 10(-5) to 2.80 x 10(-5)) and nucleotide substitutions to accrue in the consensus sequence at an average rate of 1.5 substitutions per farm infection. This is a sufficiently high rate showing that detailed histories of the transmission pathways can be reliably reconstructed. Coalescent methods indicated that the date at which FMDV first infected livestock in the United Kingdom was 7 February 2001 (95% CI, 20 January to 19 February 2001), which was identical to estimates obtained on the basis of purely clinical evidence. Nucleotide changes appeared to have occurred evenly across the genome, and within the open reading frame, the ratio of nonsynonymous-to-synonymous change was 0.09. The ability to recover particular transmission pathways of acutely acting RNA pathogens from genetic data will help resolve uncertainties about how virus is spread and could help in the control of future epidemics.


title: Colorectal endoscopic submucosal dissection: a systematic review and meta-analysis.

text: Background and study aims: Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique that allows en-bloc resection of gastrointestinal tumor. We systematically review the medical literature in order to evaluate the safety and efficacy of colorectal ESD. Patients and methods: We performed a comprehensive literature search of MEDLINE, EMBASE, Ovid, CINAHL, and Cochrane for studies reporting on the clinical efficacy and safety profile of colorectal ESD. Results: Included in this study were 13833 tumors in 13603 patients (42 % female) who underwent colorectal ESD between 1998 and 2014. The R0 resection rate was 83 % (95 % CI, 80 - 86 %) with significant between-study heterogeneity (P < 0.001) which was partly explained by difference in continent (P = 0.004), study design (P = 0.04), duration of the procedure (P = 0.009), and, marginally, by average tumor size (P = 0.09). Endoscopic en bloc and curative resection rates were 92 % (95 % CI, 90 - 94 %) and 86 % (95 % CI, 80 - 90 %), respectively. The rates of immediate and delayed perforation were 4.2 % (95 % CI, 3.5 - 5.0 %) and 0.22 % (95 % CI, 0.11 - 0.46 %), respectively, while rates of immediate and delayed major bleeding were 0.75 % (95 % CI, 0.31 - 1.8 %) and 2.1 % (95 % CI, 1.6 - 2.6 %). After an average postoperative follow up of 19 months, the rate of tumor recurrence was 0.04 % (95 % CI, 0.01 - 0.31) among those with R0 resection and 3.6 % (95 % CI, 1.4 - 8.8 %) among those without R0 resection. Overall, irrespective of the resection status, recurrence rate was 1.0 % (95 % CI, 0.42 - 2.1 %). Conclusions: Our meta-analysis, the largest and most comprehensive assessment of colorectal ESD to date, showed that colorectal ESD is safe and effective for colorectal tumors and warrants consideration as first-line therapy when an expert operator is available.


title: Fifteen years post-SARS: Key milestones in Canada's public health emergency response.

text: This year marks the 15th anniversary of Severe Acute Respiratory Syndrome (SARS) in Canada and the 100th anniversary of the 1918 Spanish influenza pandemic. These, and other recent public health events, provide an opportunity for us to review and reflect on the evolution of Canada's public health emergency response over the past 15 years-from SARS, to the 2009 H1N1 pandemic influenza, to Ebola virus and Zika virus disease. Key lessons have been learned and milestones achieved that have shaped and sharpened our response approach and structures. While SARS was a wake-up-call to strengthen infection prevention and control capacity in health care settings and led to the formation of the Public Health Agency of Canada, it also strengthened our Federal/Provincial/Territorial (FPT) senior-level governance and led to agreements for pan-Canadian mutual aid and infectious disease information sharing. As well, our collective public health laboratory capacity has been strengthened through ongoing response and sharing of advanced diagnostics and research. As we move forward, it will be important to explore the design of scalable or modular emergency response strategies and structures that are socio-culturally appropriate and employ evidence-based strategic risk communications that continue to be critical, especially given the volume and spread of misinformation. With the current global reality, we must recognize that public health threats that go unchecked anywhere in the world have the potential to very rapidly become a public health threat in Canada. We need to build, maintain and share our best public health practices globally, for we neglect these at our peril.


A report from the Communicable Diseases Network Australia, January to March 2004.


title: [Current status for urpper tract transitional cell carcinoma during COVID-19 pandemia.]

text: INTRODUCTION First cases of COVID-19 were reported in China on December 2019 and rapidly spread globally. The explosive increase in number of cases requiring hospitalization has led to a delay in a big number of surgical interventions, including oncologic surgeries. Collateral effects of this increase means a challenge for urologists, who have been forced to redistribute their resources. Due to its poor pronostic, patients suffering from by upper tract urinary tumours will be negatively affected by this pandemic. METHODS: A non sistematic review was performed using literature published until May 23, 2020, using "Uppertract urothelial tumours", "COVID-19" and "nephroureterectomy".as keywords. The resulting manuscript was critically revised by national authors in order to establish common criteria about treatment and follow up. EVIDENCE SYNTHESIS: Four studies were identified that assessed the impact of delaying radical nephrouretrectomy as curative treatment. These studies showed that surgery delays decrease overall survival and cancer specific survival rates in high-risk groups. On the other hand, delaying radical nephrouretrectomy due to ureteroscopy did not affect survival in cohorts of patients with predominately low-grade disease. CONCLUSIONS: A delay in curative treatment of upper tract urothelial tumours for more than three months results in adverse outcomes as overal survival and cancer specific survival. Hence, it is important to prioritize the timely care of this group of patients as far as COVID-19 pandemic allows it.


title: [Severe acute respiratory syndrome--SARS].

text: Severe Acute Respiratory Syndrome (SARS) is an acute respiratory illness caused by SARS coronavirus. This virus was possibly transmitted from an animal reservoir to humans, and from February 2003, the epidemic was spread internationally by further person-to-person transmission. The SARS epidemic was managed by well-known principles of infection control, including prompt diagnosis, isolation of patients, and quarantine of contacts. The successful control of the outbreak is a remarkable international achievement, though much about SARS remains poorly understood.


title: Lactate dehydrogenase-elevating virus variants: cosegregation of neuropathogenicity and impaired capability for high viremic persistent infection.

text: Neuropathogenic isolates of lactate dehydrogenase virus (LDV) differ from non-neuropathogenic isolates in their unique ability to cause a paralytic disease (age-dependent poliomyelitis, ADPM) in immunosuppressed C58 and AKR mice by cytocidally infecting their anterior horn neurons. We have recently reported that an original neuropathogenic LDV isolate, LDV-C-BR, contained a low level of a coexisting non-neuropathogenic LDV which, in a mixed infection of mice, rapidly outcompeted the former resulting in apparent loss of neuropathogenicity of the reisolated LDV. This correlated with an impaired ability of the neuropathogenic LDV to establish a viremic persistent infection. In the present study we identified the presence of three different quasispecies in another original neuropathogenic LDV by sequence analysis of cDNA clones of ORF 5 (encoding the primary envelope glycoprotein VP-3P) obtained from the isolate. Successful development of differential reverse transcription-polymerase chain reaction assays allowed us to biologically clone all three quasispecies through repeated end point dilutions. Only one of the quasispecies (LDV-v) was neuropathogenic. The other two, LDV-vP (probably the same as LDV-P) and LDV-vx (a novel LDV quasispecies that had not been previously identified), were non-neuropathogenic and found to be the common LDV quasispecies associated with almost all LDVs originally isolated from mice carrying various other transplantable tumors. The neuropathogenic LDV-v became selectively amplified in the spinal cords of paralyzed mice, but possessed an impaired ability to establish a persistent viremic infection and was rapidly out-competed by LDV-vP and LDV-vx in mixed infections, just as reported previously for LDV-C-BR. The results further support our hypothesis that neuropathogenicity and impaired capability for viremic persistence of LDV are determined by the same molecular feature. The only consistent and biologically relevant molecular difference we have observed between neuropathogenic and non-neuropathogenic LDVs is the number of polylactosaminoglycan chains associated with the ectodomain of VP-3P.


title: Comparison of different ligation techniques in laparoscopic varicocelectomy.

text: AIM To evaluate the effects of different intracorporeal ligation techniques with titanium clips, Plasma Trisector (Gyrus, USA) (PTG), and surgical silk on bilateral laparoscopic varicocelectomy (LPVx). MATERIALS AND METHODS Between May 2009 and August 2012, 100 patients who underwent bilateral LPVx were evaluated. The demographic parameters of patients, preoperative radiological findings, semen analysis, operative data, and follow-up were recorded. All of the patients were divided into 3 groups, randomized prospectively. The patients whose veins were ligated by 5-mm titanium clips were included in group I, those whose veins were ligated by PTG were included in group II, and those whose veins were ligated by surgical silk were included in group III. The recorded data of the groups were analyzed. RESULTS Mean follow-up time was 18.8 + 1.1 months. According to the demographics of age, body mass index, spermiogram, and diameter of veins before surgery, there were no statistical differences between any of the groups (P > 0.05). However, operation time was longer in group III (P < 0.0001), while total numbers ofligated veins did not differ among the groups (P > 0.05). Additionally, hospital stay, oral intake, and complications were not different among the groups (P > 0.05). In follow-up the sperm count analysis was higher than the preoperative count analysis for all of the groups (P < 0.05). CONCLUSION PTG may provide a shorter operation time than using titanium clips and/or surgical silk in LPVx. Additionally, PTG may increase sperm count with fewer complications than the other ligation techniques in LPVx. Therefore, PTG may be the new candidate electrosurgical standard device for LPVx in the nearby future.


title: Isolation of respiratory bovine coronavirus, other cytocidal viruses, and Pasteurella spp from cattle involved in two natural outbreaks of shipping fever.

text: OBJECTIVE To identify cytocidal viruses and Pasteurella spp that could be isolated from cattle involved in 2 natural outbreaks of shipping fever. ANIMALS 105 and 120 castrated male 4- to 8-month-old feedlot cattle involved in 1997 and 1998 outbreaks, respectively. PROCEDURES Nasal swab specimens and blood samples were collected, and cattle were vaccinated on arrival at an order-buyer barn from 4 local auction houses. Four days later, they were transported to a feedlot, and additional nasal swab specimens and blood samples were collected. Nasal swab specimens were submitted for virus isolation and bacterial culture; blood samples were submitted for measurement of respiratory bovine coronavirus (RBCV) hemagglutinin inhibition titers. RESULTS 93 of 105 cattle and 106 of 120 cattle developed signs of respiratory tract disease during 1997 and 1998, respectively, and RBCV was isolated from 81 and 89 sick cattle, respectively, while at the order-buyer's barn or the day after arrival at the feedlot. During the 1997 outbreak, bovine herpesvirus 1 was isolated from 2 cattle at the order-buyer's barn and from 5 cattle 7 and 14 days after arrival at the feedlot, and parainfluenza virus 3 was isolated from 4 cattle 14 days after arrival at the feedlot. During the 1998 outbreak, bovine herpesvirus 1 was isolated from 2 cattle at the order-buyer's barn and on arrival at the feedlot and from 5 cattle 7 and 14 days after arrival at the feedlot, and parainfluenza virus 3 was isolated from 1 animal the day of, and from 18 cattle 7 and 14 days after, arrival at the feedlot. Pasteurella spp was cultured from 4 and 6 cattle at the order-buyer's barn and from 92 and 72 cattle on arrival at the feedlot during the 1997 and 1998 outbreaks, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that RBCV may play a causative role in outbreaks of shipping fever in cattle. More than 80% of the sick cattle shed RBCV at the beginning of 2 outbreaks when the Pasteurella spp infection rate was low.


title: Studies on the mechanism of RNA synthesis of a murine coronavirus.

text: The mechanism of viral RNA replication in mouse hepatitis virus (MHV)-infected cells was studied by oligonucleotide mapping of every mRNA. We discovered that an oligonucleotide, No. 10, was localized at the 5'-end of every mRNA, and was not colinear with the sequences of the virion genomic RNA. This result indicates that all of the mRNAs contain a leader sequence which is joined to the body sequences of the mRNAs. We have also studied the structure of the replicative intermediate (RI) RNA in the MHV-infected cells. This RI RNA consists of a single species corresponding to the MHV genomic RNA. No subgenomic RI structures were detected. Furthermore, the nascent RNA chains in the RI structure contained the leader sequences, suggesting that the leader RNA was not added to the mRNA post- transcriptionally , but rather, it was probably synthesized independently and then used as a primer for the synthesis of mRNAs. We have also shown that the poly (A) sequences in the MHV genome were transcribed from the poly (U) sequences present in the negative-strand template. The RNA polymerases involved in the MHV RNA synthesis were also characterized. The early polymerase synthesizes a single negative-stranded, full-length RNA. The late polymerases could be separated into two activities, one synthesizing positive-stranded genomic RNA, and the other synthesizing genomic as well as subgenomic RNAs. Thus, the replication and transcription functions of MHV could probably be separated. A plausible model of MHV replication is presented.


title: Open inguinal hernia repair with self-gripping Parietex ProGrip mesh: a retrospective study of 204 cases.

text: Chronic pain and recurrence rates are the main challenge in modern inguinal hernia surgery. Several trials have investigated the role of self-adhesive mesh repair for inguinal hernia, with special attention to the incidence of chronic postoperative inguinal pain and recurrence. The purpose of our study was to retrospectively evaluate the early and long-term results using a self-gripping mesh (Parietex Progrip® , Covidien) in our institution. A total of 204 patients, mean age 50.3 standard deviation (SD) 15.3, was included in the study. The repair was performed under local anaesthesia in 159 (78%) cases and locoregional anaesthesia in remaining 45 (22%). Mean operative time was 39 ± 20 minutes. The time for self-gripping mesh placement ranged from 5 to 9 minutes (mean 7 ± 2 minutes). There were no intraoperative complications. Clinical follow-up was performed at 1 month, 1 year and 2 years and consisted in the evaluation of complications, discomfort/pain and recurrence. One case of cutaneous infection and three cases of seroma were observed at one-month follow-up and were all treated conservatively. 8 patients were lost at one year follow-up, and another 4 were lost at 2 years. 3 patients died for other causes during follow-up. At 1 year and 2 years follow-up no cases of seroma, testicular complications or mesh infection were observed. Two cases of recurrence were recorded at 2 years follow up. No patient reported VAS score > 2 at one month, 1 year and 2 years follow-up. There were no readmissions, systemic complications or death during 2 years follow-up. Lichtenstein open repair using Parietex Progrip® mesh is a simple, rapid, effective and safe method for inguinal hernia repair. The main advantage of self-fixing mesh is the reduced operative time. A suturless fixation seems to prevent the development of postoperative chronic pain, without increasing recurrence rate in the majority of the trials.


docid: rkldrqfe

title: Andes and Prospect Hill hantaviruses differ in early induction of interferon although both can downregulate interferon signaling.

text: Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease which is thought to result from a dysregulated immune response to infection with pathogenic hantaviruses, such as Sin Nombre virus or Andes virus (ANDV). Other New World hantaviruses, such as Prospect Hill virus (PHV), have not been associated with human disease. Activation of an antiviral state and cell signaling in response to hantavirus infection were examined using human primary lung endothelial cells, the main target cell infected in HPS patients. PHV, but not ANDV, was found to induce a robust beta interferon (IFN-beta) response early after infection of primary lung endothelial cells. The level of IFN induction correlated with IFN regulatory factor 3 (IRF-3) activation, in that IRF-3 dimerization and nuclear translocation were detected in PHV but not ANDV infection. In addition, phosphorylated Stat-1/2 levels were significantly lower in the ANDV-infected cells relative to PHV. Presumably, this reflects the lower level of IRF-3 activation and initial IFN induced by ANDV relative to PHV. To determine whether, in addition, ANDV interference with IFN signaling also contributed to the low Stat-1/2 activation seen in ANDV infection, the levels of exogenous IFN-beta-induced Stat-1/2 activation detectable in uninfected versus ANDV- or PHV-infected Vero-E6 cells were examined. Surprisingly, both viruses were found to downregulate IFN-induced Stat-1/2 activation. Analysis of cells transiently expressing only ANDV or PHV glycoproteins implicated these proteins in this downregulation. In conclusion, while both viruses can interfere with IFN signaling, there is a major difference in the initial interferon induction via IRF-3 activation between ANDV and PHV in infected primary endothelial cells, and this correlates with the reported differences in pathogenicity of these viruses.


title: Importance of the positive-strand RNA secondary structure of a murine coronavirus defective interfering RNA internal replication signal in positive-strand RNA synthesis.

text: The RNA elements that are required for replication of defective interfering (DI) RNA of the JHM strain of mouse hepatitis virus (MHV) consist of three discontinuous genomic regions: about 0.46 to 0.47 kb from both terminal sequences and an internal 58-nucleotide (nt)-long sequence (58-nt region) present at about 0.9 kb from the 5' end of the DI genome. The internal region is important for positive-strand DI RNA synthesis (Y. N. Kim and S. Makino, J. Virol. 69:4963-4971, 1995). We further characterized the 58-nt region in the present study and obtained the following results. (i) The positive-strand RNA structure in solution was comparable with that predicted by computer modeling. (ii) Positive-strand RNA secondary structure, but not negative-strand RNA structure, was important for the biological function of the region. (iii) The biological function had a sequence-specific requirement. We discuss possible mechanisms by which the internal cis-acting signal drives MHV positive-strand DI RNA synthesis.


title: Modelling respiratory infection control measure effects.

text: One of the most pressing issues in facing emerging and re-emerging respiratory infections is how to bring them under control with current public health measures. Approaches such as the Wells-Riley equation, competing-risks model, and Von Foerster equation are used to prioritize control-measure efforts. Here we formulate how to integrate those three different types of functional relationship to construct easy-to-use and easy-to-interpret critical-control lines that help determine optimally the intervention strategies for containing airborne infections. We show that a combination of assigned effective public health interventions and enhanced engineering control measures would have a high probability for containing airborne infection. We suggest that integrated analysis to enhance modelling the impact of potential control measures against airborne infections presents an opportunity to assess risks and benefits. We demonstrate the approach with examples of optimal control measures to prioritize respiratory infections of severe acute respiratory syndrome (SARS), influenza, measles, and chickenpox.


title: Management of a case with misdiagnosed spinal dural arterio-venous fistula.

text: PURPOSE Spinal dural arterio-venous fistula (SDAVF) is an uncommon and easily misdiagnosed vascular malformation. We aimed to report the diagnosis and management of a case with SDAVF. CASE REPORT A 62-year-old man suffered from acute paraparesis about 15 months before this study. He underwent a neurosurgical procedure for herniated discs of the cervical spine at that time but there was no relief and the symptoms worsened despite the surgery. Neurologically, he had spastic paraparesis and decreased vibration sensation of the lower limbs. Spinal magnetic resonance imaging (MRI) revealed intra-medullary hyper-intensity lesion at T8 to T10 levels and tubular-like signal void structures in the corresponding posterior sub-arachnoid space. Further trans-arterial angiography through right T6 intercostal artery catheterization revealed engorged veins, thereby confirming the diagnosis of SDAVF. The patient was treated via endovascular embolization (18% Onyx, EV3TM MIT, Bonn, Germany) through spinal angiography and the results showed a marked decrease in engorged veins. After a 4-month follow-up, the patient was symptomatic but stable. Follow-up MRI showed a complete disappearance of the hyper-intensity change of the spinal cord. Spinal MR angiography did not reveal any recurrence of SDAVF. CONCLUSION This case study demonstrated the easily misdiagnosed state of SDAVF. Serial neuroimage studies including spinal MRI, endovascular embolization through spinal angiography and MR angiography can be useful tools for its diagnostic confirmation, management and follow-up study.


ACCF/AHA/CDC conference report on emerging infectious diseases and biological terrorism threats. Task Force I: direct cardiovascular implications of emerging infectious diseases and biological terrorism threats.


title: Bioactive coumarins from Boenninghausenia sessilicarpa.

text: Bioassay guided fractionation of Boenninghausenia sessilicarpa (Rutaceae) resulted in the isolation of a new dimeric coumarin glucoside 9'-methoxyl rutarensin (1) and a cytotoxic compound rutamarin (4), as well as an antivirus component leptodactylone (8), together with six known coumarins. Their structures were elucidated by 1D- and 2D NMR spectroscopy and ESI-MS analyses, respectively. Rutamarin (4) showed significant inhibitory activities against A-549, Bel-7402, HepG-2 and HCT-8 tumour cell lines with IC50s of 1.318, 2.082, 2.306 and 2.497 microg/ml. In addition, leptodactylone (8) showed potent protective activity on cells infected by SARS-CoV with ratio of 60% at 100 microg/ml.


Severe acute respiratory syndrome: lab accidents prompt calls for new containment program.


title: Awareness With Recall: A Systematic Review.

text: This article provides a systematic review of awareness with recall, also called intraoperative awareness. Major topics of this review include the incidence and causes of this phenomenon, in addition to an examination of current strategies for prevention of intraoperative awareness. Awareness with recall creates substantial physical and/or psychological distress for the patient, representing a continued threat to patient safety. Factors related to cases of awareness include those of the patient, surgical procedure, anesthesia provider, and system in which providers deliver care. Anesthesia providers today consider use of electroencephalographic depth-of-anesthesia monitors such as the bispectral index monitor (BIS, Covidien, now Medtronic), as a potential tool for preventing awareness. This Journal course explores evidence related to the utility and limitations of this monitor in clinical practice. It also reviews evidence-based practices that may decrease the incidence of awareness with recall, including avoidance of muscle relaxants and protocol-driven approaches to awareness prevention.


title: Degenerative changes in neutrophils: an indicator of bacterial infection.

text: A review was made of 195 peripheral blood smears of 157 neonates who required sepsis work-up in the first month of life. Degenerative changes of neutrophils including vacuolization and toxic granulation were observed frequently in infants with culture-proven bacterial sepsis. Of 21 peripheral blood smears from 20 neonates subsequently proven to have bacterial infection, 17 had vacuolization present in the neutrophils for a sensitivity of 81%, a specificity of 93%, and a positive predictive accuracy of 59%. Toxic granulation changes in neutrophils showed similar results. This simple test can be performed easily in all hospitals; it does not require special laboratory facilities. The test appears to provide a valuable adjunct in the early detection of neonatal bacterial infection.


title: Synthesis and characterization of a native, oligomeric form of recombinant severe acute respiratory syndrome coronavirus spike glycoprotein.

text: We have expressed and characterized the severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein in cDNA-transfected mammalian cells. The full-length spike protein (S) was newly synthesized as an endoglycosidase H (endo H)-sensitive glycoprotein (gp170) that is further modified into an endo H-resistant glycoprotein (gp180) in the Golgi apparatus. No substantial proteolytic cleavage of S was observed, suggesting that S is not processed into head (S1) and stalk (S2) domains as observed for certain other coronaviruses. While the expressed full-length S glycoprotein was exclusively cell associated, a truncation of S by excluding the C-terminal transmembrane and cytoplasmic tail domains resulted in the expression of an endoplasmic reticulum-localized glycoprotein (gp160) as well as a Golgi-specific form (gp170) which was ultimately secreted into the cell culture medium. Chemical cross-linking, thermal denaturation, and size fractionation analyses suggested that the full-length S glycoprotein of SARS-CoV forms a higher order structure of approximately 500 kDa, which is consistent with it being an S homotrimer. The latter was also observed in purified virions. The intracellular form of the C-terminally truncated S protein (but not the secreted form) also forms trimers, but with much less efficiency than full-length S. Deglycosylation of the full-length homotrimer with peptide N-glycosidase-F under native conditions abolished recognition of the protein by virus-neutralizing antisera raised against purified virions, suggesting the importance of the carbohydrate in the correct folding of the S protein. These data should aid in the design of recombinant vaccine antigens to prevent the spread of this emerging pathogen.


title: Difficult-to-Detect Low-Grade Infections Responsible for Poor Outcomes in Total Knee Arthroplasty.

text: In this article, we present the case of a patient with a stiff, painful knee after total knee arthroplasty, and with erythrocyte sedimentation rate, C-reactive protein level, and synovial fluid analysis within normal limits. Open biopsy for cultures showed Propionibacterium acnes prosthetic joint infection, which was successfully treated with 2-stage revision and intravenous antibiotics.


title: Processing of a cellular polypeptide by 3CD proteinase is required for poliovirus ribonucleoprotein complex formation.

text: Poliovirus interactions with host cells were investigated by studying the formation of ribonucleoprotein complexes at the 3' end of poliovirus negative-strand RNA which are presumed to be involved in viral RNA synthesis. It was previously shown that two host cell proteins with molecular masses of 36 and 38 kDa bind to the 3' end of viral negative-strand RNA at approximately 3 to 4 h after infection. We tested the hypothesis that preexisting cellular proteins are modified during the course of infection and are subsequently recruited to play a role in viral replication. It was demonstrated that the 38-kDa protein, either directly or indirectly, is the product of processing by poliovirus 3CD/3C proteinase. Only the modified 38-kDa protein, not its precursor protein, has a high affinity for binding to the 3' end of viral negative-strand RNA. This modification depends on proteolytically active proteinase, and a direct correlation between the levels of 3CD proteinase and the 38-kDa protein was demonstrated in infected tissue culture cells. The nucleotide (nt) 5-10 region (positive-strand numbers) of poliovirus negative-strand RNA is important for binding of the 38-kDa protein. Deletion of the nt 5-10 region in full-length, positive-strand RNA renders the RNA noninfectious in transfection experiments. These results suggest that poliovirus 3CD/3C proteinase processes a cellular protein which then plays an essential role during the viral life cycle.


title: Intubation without use of stylet for McGrath videolaryngoscopy in patients with expected normal airway: A randomized noninferiority trial.

text: BACKGROUND During McGrath videolaryngoscope (VL) intubation, a styletted endotracheal tube maintaining an upward distal tip angle is recommended by some manufacturers. However, a styletted endotracheal tube can elicit rare but potentially serious complications. The purpose of this study was to demonstrate that a nonstyletted tube with exaggerated curvature would be noninferior to a styletted tube for orotracheal intubation using McGrath VL in patients with expected normal airway, by comparing the time to intubation and ease of intubation. METHODS One hundred forty patients, ages 19 to 70 years (American Society of Anesthesiologists physical status I-II), undergoing tracheal intubation for elective surgery were randomly allocated to the nonstylet group (n = 70) or the stylet group (n = 70). Anesthesia induction consisted of propofol, remifentanil, and rocuronium. The primary outcome was time to intubation assessed by a blind observer. Cormack and Lehane glottic grade, easy of intubation, and intubation difficulty score (IDS) were also assessed. RESULTS Median time to intubation [interquartile range] was not different between the nonstylet group and the stylet group (26 [24-32.5] s vs 27 [25-31] s, P = 0.937). There was no significant in median IDS between the nonstylet group and the stylet group (P = 0.695). CONCLUSION This study shows that a nonstyletted endotracheal tube with exaggerated curvature has a similar performance to a styletted tube with a hockey-stick curvature during intubation using McGrath VL regarding time taken to successful intubation and easiness of intubation.


title: Chicken egg yolk antibodies as therapeutics in enteric infectious disease: a review.

text: Passive immunization by oral administration of specific antibodies has been an attractive approach against gastrointestinal (GI) pathogens in both humans and animals. Recently, laying chickens have attracted considerable attention as an alternative source of antibodies for the prevention and treatment of infectious GI diseases. After immunization, the specific antibodies (called IgY) are transported to the egg yolk, from which the IgY then can be separated without sacrificing chickens. A chicken usually lays about 280 eggs in a year, and egg yolk contains 100-150 mg of IgY per yolk, suggesting that more than 40 g of IgY per year can be obtained from each chicken through eggs. IgY is also an alternative to antibiotics for treatment of enteric antibiotic-resistant pathogens. Oral administration of IgY has proved successful for treatment of a variety of GI infections, such as bovine and human rotaviruses, bovine coronavirus, Yersinia ruckeri, enterotoxigenic Escherichia coli, Salmonella spp., Edwardsiella tarda, Staphylococcus, and Pseudomonas. The IgY technology offers great future opportunities for designing prophylactic strategies against infectious GI diseases in humans and animals. However, there is still controversy regarding the stability of IgY through the GI tract. Finding an effective way to protect the antibodies from degradation in the GI tract would open the door for significant advances in IgY technology and nutraceutical applications.


title: Diagnosing COVID-19: Did We Miss Anything?

text: In late 2019, a mass of patients showing symptoms of a pneumonia-like disease of unknown origin emerged in Wuhan, China. Little did the world know it was the prelude of what would be a devastating pandemic. Samples were collected from these patients and the use of unbiased sequencing, and subsequent isolation of the pathogen using human airway epithelial cells led to the discovery of a novel coronavirus, named 2019-nCoV by the World Health Organization (WHO) and Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The disease caused by this virus is officially called the coronavirus disease 2019 (COVID-19).


docid: eocvupyv

title: New Technique: Acute Minced Expansion Graft of Traumatic Wound Tissue.

text: OBJECTIVES Superficial soft tissue injury, such as a skin tear, is common. For such wounds, the authors introduce a novel technique that allows the physician to salvage otherwise discarded tissue as a traumatic graft to highly accelerate wound healing. METHODS A series of 11 patients with superficial soft tissue trauma in which debrided tissues are salvaged back into the wound by means of minced expansion grafting (MEG) are followed from presentation through healing. RESULTS Salvaged tissue replaced back into wounds as MEG grafts greatly accelerated epithelialization and wound closure. CONCLUSIONS Based on their experience with MEG, the authors introduce a new principle for the wound surgeon that no tissue should ever be discarded, but rather salvaged and placed back into the wound.


Severe acute respiratory syndrome--Singapore, 2003.


title: Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus.

text: OBJECTIVES To identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics. METHODS 48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition. CONCLUSION Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.


title: Pathogen-directed therapy in acute exacerbations of chronic obstructive pulmonary disease.

text: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of this chronic lung disorder. These events can be caused by a large number of infectious and noninfectious agents and are associated with an increased local and systemic inflammatory response. Their frequency and severity have been linked to progressive deterioration in lung function and health status. Infectious pathogens ranging from viral to atypical and typical bacteria have been implicated in the majority of episodes. Most therapeutic regimens to date have emphasized broad, nonspecific approaches to bronchoconstriction and pulmonary inflammation. Increasingly, therapy that targets specific etiologic pathogens has been advocated. These include clinical and laboratory-based methods to identify bacterial infections. Further additional investigation has suggested specific pathogens within this broad class. As specific antiviral therapies become available, better diagnostic approaches to identify specific pathogens will be required. Furthermore, prophylactic therapy for at-risk individuals during high-risk times may become a standard therapeutic approach. As such, the future will likely include aggressive diagnostic algorithms based on the combination of clinical syndromes and rapid laboratory modalities to identify specific causative bacteria or viruses.


title: Biomarkers: mining the biofluid proteome.

text: Proteomics has brought with it the hope of identifying novel biomarkers for diseases such as cancer. This hope is built on the ability of proteomic technologies, such as mass spectrometry (MS), to identify hundreds of proteins in complex biofluids such as plasma and serum. There are many factors that make this research very challenging beginning with the lack of standardization of sample collection and continuing through the entire analytical process. Fortunately the advances made in the characterization of biofluids using proteomic techniques have been rapid and suggest that these mainly discovery driven approaches will lead to the development of highly specific platforms for diagnosing diseases and monitoring responses to different treatments in the near future.


title: Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations.

text: RATIONALE Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalization. The role of infections in COPD exacerbations is controversial. OBJECTIVES We investigated whether COPD exacerbations requiring hospitalization are associated with viral and/or bacterial infection and evaluated relationships among infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. METHODS We examined 64 patients with COPD when hospitalized for exacerbations, and when in stable convalescence. We measured lung function, blood gases, and exhaled nitric oxide, and examined sputum for inflammation and for viral and bacterial infection. RESULTS Exacerbations were associated with impaired lung function (p < 0.01) and increased sputum neutrophilia (p < 0.001). Viral and/or bacterial infection was detected in 78% of exacerbations: viruses in 48.4% (6.2% when stable, p < 0.001) and bacteria in 54.7% (37.5% when stable, p = 0.08). Patients with infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial coinfection) had longer hospitalizations (p < 0.02) and greater impairment of several measures of lung function (all p < 0.05) than those with noninfectious exacerbations. Patients with exacerbations with coinfection had more marked lung function impairment (p < 0.02) and longer hospitalizations (p = 0.001). Sputum neutrophils were increased in all exacerbations (p < 0.001) and were related to their severity (p < 0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (p < 0.001) virus-associated exacerbations. CONCLUSIONS Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial coinfection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.


Revision of the Canadian Emergency Department Information System (CEDIS) Presenting Complaint List version 1.1.


title: Hemodynamic Monitoring in the Acute Management of Pediatric Heart Failure.

text: One of the basic tenets of cardiac critical care is to ensure adequate tissue oxygenation. As with other critical illness such as trauma and acute myocardial infarction studies have demonstrated that making the right diagnosis at the right time improves outcomes. The same is true for the management of patients at risk for or in a state of shock. In order to optimize outcomes an accurate and timely assessment of cardiac function, cardiac output and tissue oxygenation must be made. This review discusses the limitations of the standard assessment of cardiovascular function, and adjunctive monitoring modalities that may be used to enhance the accuracy and timely implementation of therapeutic strategies to improve tissue oxygenation.


docid: jwbpbkbw

title: Therapeutic potential of the new quinolones in the treatment of lower respiratory tract infections.

text: The impact of respiratory infections on public health is increasing and lower respiratory tract infections are a major cause of morbidity and mortality. We are also facing a worldwide burst of antibiotic bacterial resistance. The new fluoroquinolones have an excellent spectrum covering the most important respiratory pathogens, including atypical and 'typical' pathogens. Pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained postantibiotic effect. Fluoroquinolones combine exceptional efficacy with cost-effectiveness. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of community-acquired pneumonia. This review discusses the more recent data on bacteriological and clinical activity and critically analyses the risks of a potential overuse of this valuable new class of drugs.


title: Efficacy and Tolerability of High-dose Pelargonium Extract in Patients With the Common Cold.

text: Context • The common cold (CC) is usually caused by a viral infection. Antibiotics are often prescribed unnecessarily for it, although no evidence exists for any benefit in the CC. Effective alternatives are needed. Objective • The study intended to evaluate the efficacy of 7630, a proprietary extract of Pelargonium sidoides, the active ingredient in umckaloabo, compared with a placebo for the treatment of the CC. Design • This was a prospective, double-blind, parallel-group, placebo-controlled, phase 3 clinical trial (RCT), with an adaptive group-sequential design with 2 parts, both of which were 2-arm trials. The first used a standard dose (SD) of 3 × 30 drops per day of the active medication and the second used a high dose (HD) of 3 × 60 drops per day of the active medication, against 3 × 30 drops per day and 3 × 60 drops per day of a placebo, respectively. Setting • The study took place in 8 outpatient departments affiliated with hospitals. Participants • For the entire study, 207 adults with predefined cold symptoms that had been present for 24 to 48 h prior were included in the study, with 103 participating in the SD part and 104 participating in the HD part. Intervention • In the HD part, as covered in this article, the intervention group received treatment with 3 × 60 drops per day of the active medication and the control group received a placebo (control group), for a maximum period of 10 d. Outcome Measures • The primary outcome measure was the sum of differences in the cold intensity score (CIS) from day 1 to day 3 and from day 1 to day 5, defined as the sum of the symptom intensity differences (SSID). The criteria for the secondary outcome, efficacy, were (1) diverse response criteria according to the total CIS; (2) changes in individual CIS symptoms; (3) changes in further cold-relevant symptoms; (4) ability to work; (5) activity level; (6) general well-being; (7) health-related quality of life-the EuroQol questionnaire with 5 dimensions (EQ-5D), including the visual analogue scale EQ-VAS; (8) time until onset of treatment effect; (9) treatment outcome; and (10) satisfaction with treatment. Results • From baseline to day 5, the mean CIS decreased by 11.2 ± 4.8 points for the 7630 group and 6.3 ± 4.7 points for the control group. The mean SSID was 16.0 ± 7.6 points for the control group (P < .0001). After 10 d, 90.4% of the group receiving the active medication and 21.2% of the control group were clinically cured (P < .0001). In the treatment group, participants' inability to work was significantly lower, with a mean duration of 6.4 ± 1.6 d vs 8.3 ± 2.1 d for the control group (P < .0001), and treatment outcome-complete recovery or major improvement-was significantly better at day 5 for the active treatment group compared with the control group (P < .0001). Mild-to-moderate adverse events-all nonserious-occurred in 15.4% of those receiving active treatment vs in 5.8% for the control group. Conclusions • The active medication is an effective, well tolerated, and safe treatment for the CC. It significantly reduces the severity of symptoms and shortens the duration of the disease.


title: Induction of caspase-dependent apoptosis in cultured rat oligodendrocytes by murine coronavirus is mediated during cell entry and does not require virus replication.

text: Murine coronavirus mouse hepatitis virus (MHV) causes demyelination of the central nervous system (CNS) in rats and mice. Apoptotic oligodendrocytes have been detected in the vicinity of the CNS demyelinating lesions in these animals. However, whether MHV can directly induce oligodendrocyte apoptosis has not been documented. Here, we established a rat oligodendrocyte culture that is morphologically and phenotypically indistinguishable from the primary rat oligodendrocytes. Using this culture, we showed that mature rat oligodendrocytes were permissive to MHV infection but did not support productive virus replication. Significantly, oligodendrocytes infected with both live and ultraviolet light-inactivated viruses underwent apoptosis to a similar extent, which was readily detectable at 24 h postinfection as revealed by apoptotic bodies and DNA fragmentation, indicating that MHV-induced apoptosis is mediated during the early stages of the virus life cycle and does not require virus replication. Prior treatment of cells with the lysosomotropic agents NH(4)Cl and chloroquine as well as the vacuolar proton pump-ATPase inhibitor bafilomycin A1, all of which block the acidification of the endosome, prevented oligodendrocytes from succumbing to apoptosis induced by MHV mutant OBLV60, which enters cells via endocytosis, indicating that fusion between the viral envelope and cell membranes triggers the apoptotic cascade. Treatment with the pan-caspase inhibitor Z-VAD-fmk blocked MHV-induced apoptosis, suggesting an involvement of the caspase-dependent pathway. Our results, thus, for the first time provide unequivocal evidence that infection of oligodendrocytes with MHV directly results in apoptosis. This finding provides an explanation for the destruction of oligodendrocytes and the damage of myelin sheath in MHV-infected CNS and suggests that oligodendrocyte apoptosis may be one of the underlying mechanisms for the pathogenesis of MHV-induced demyelinating diseases in animals.


title: Prospective randomized comparison of open versus laparoscopic management of splenic artery aneurysms: a 10-year study.

text: BACKGROUND: The literature does not support the choice between open and laparoscopic management of splenic artery aneurysms (SAA). METHODS: We designed a prospective, randomized comparison between open and laparoscopic surgery for SAA. Primary end points were types of surgical procedures performed and clinical outcomes. Analysis was developed on an intention-to-treat basis. RESULTS: Fourteen patients were allocated to laparotomy (group A) and 15 to laparoscopy (group B). Groups displayed similar patient- and aneurysm-related characteristics. The conversion rate to open surgery was 13.3 %. The type of surgical procedure performed on the splenic artery was similar in the two groups: aneurysmectomy with splenic artery ligature or direct anastomosis was performed in 51 % and 21 % of patients in group A and in 60 % and 20 % in group B, respectively. The splenectomy rate was similar (14 % vs. 20 %). Postoperative splenic infarction was observed in one case in each group. Laparoscopy was associated with shorter procedures (p = 0.0003) and lower morbidity (25 % vs. 64 %, p = 0.045). Major morbidity requiring interventional procedures and blood transfusion was observed only in group A. Laparoscopy was associated with quicker resumption of oral diet (p < 0.001), earlier drain removal (p = 0.046), and shorter hospital stay (p < 0.01). During a mean follow-up of 50 months, two patients in group A required hospital readmission. In group B, two patients developed a late thrombosis of arterial anastomoses. CONCLUSIONS: Our study demonstrates that laparoscopy permits multiple technical options, does not increase the splenectomy rate, and reduces postoperative complications. It confirms the supposed clinical benefits of laparoscopy when ablative procedures are required but laparoscopic anastomoses show poor long-term results.


title: Identification of residues critical for the human coronavirus 229E receptor function of human aminopeptidase N.

text: Aminopeptidase N (APN) is the major cell surface receptor for group 1 coronaviruses. In this study, we have isolated and characterized a feline APN cDNA and shown that the transfection of human embryonic kidney cells with this cDNA renders them susceptible to infection with the feline coronavirus feline infectious peritonitis virus, the human coronavirus (HCV) 229E and the porcine coronavirus porcine transmissible gastroenteritis virus. By using chimeric APN genes, assembled from porcine and feline sequences, we have shown that, analogously to the human APN protein, a region within the amino-terminal part of the feline APN protein (encompassing amino acids 132-295) is essential for its HCV 229E receptor function. Furthermore, by comparing the relevant feline, human and porcine APN sequences, we were able to identify a hypervariable stretch of eight amino acids that are more closely related in the feline and human APN proteins than in the porcine APN molecule. Using PCR-directed mutagenesis, we converted this stretch of amino acids within the porcine APN molecule to the corresponding residues of the human APN molecule. These changes were sufficient to convert porcine APN into a functional receptor for HCV 229E and thus define a small number of residues that are critically important for the HCV 229E receptor function of human APN.


title: SARS: a quality management test of our public health safety net.

text: Emergence of severe acute respiratory syndrome in March 2003 tested all aspects of BC Centre for Disease Control (BCCDC) operations. In addition to its public health responsibilities, BCCDC was pivotal in the science defining SARS. These events occurred under international scientific and media scrutiny over a 4-month period and were seen as an opportunity to learn about how the Centre performed under extreme pressure as a QM-based (quality-management-based) organization. A retrospective review of the QM practices over the previous 6-months was initiated on June 30, 2003. Key management documentation during the study period was reviewed. Structured interviews were conducted with front line personnel. Customized instrumentation was developed to correlate management decisions with recognized QM criteria: anticipatory management; keeping programs on track; ongoing adjustment, improvement, and revision; identifying and improving sources of error, waste, and redundancy; feedback from key stakeholders; and data-driven decision-making methods. The team structure between laboratory science and epidemiology was critical. This was attributed to the culture of scientific discovery of the organization. All knowledge gained was shared with other organizations around the world. The consensus is that British Columbia was very lucky this time around. This review is part of BCCDC's commitment to fighting emerging infectious diseases.


title: Prospective sequential endoscopic and histologic studies of the gastric pouch in 130 morbidly obese patients submitted to Roux-en-Y gastric bypass.

text: BACKGROUND Roux-en-Y gastric bypass is the most common performed bariatric surgery. A small gastric pouch is created, leaving a narrow gastrojejunal anastomosis, with a long jejunal limb. Very little is known regarding the behavior of this pouch years after surgery. AIM To determine through prospective sequential endoscopic studies the size of the gastric pouch, the diameter of the anastomosis, and the behavior of H. pylori infection after surgery. METHODS In 130 patients subjected to resectional gastric bypass, several routine sequential endoscopic (until 120 months) and histological evaluations of the gastric pouch were performed. RESULTS After surgery, a mean of 3.6 endoscopies/patient were performed. Macroscopically nearly 95% of the small gastric pouches were normal, and the main pathological finding was a marginal ulcer. Erosive esophagitis disappeared in 93% of the patients. There was no increase in the orocaudal size of the pouch during this period of observation. There was no dilatation of the diameter of gastrojejunal anastomosis. Near 54% of all patients had normal fundic mucosa, while 18% had chronic active gastritis, coincident with H. pylori infection. Five patients had intestinal metaplasia. CONCLUSION Based on this sequential endoscopic evaluation, there was no increase in the orocaudal size of the gastric pouch nor increase in the diameter of the gastrojejunal anastomosis. H. pylori behavior was inconsistent and difficult to interpret.


title: Stent/balloon combination assist technique for wide-necked basilar terminal aneurysms.

text: We describe an enhanced endovascular procedure for the coiling of broad-necked basilar terminal aneurysms with a combined balloon/stent assist technique. A balloon-assisted catheter is inserted in the origin of one posterior cerebral artery (PCA) and an assisted stent is deployed from the opposite PCA to the basilar artery. A microcatheter for coiling is inserted through the stent strut (trans-cell approach), and the aneurysm is coiled under stent support and assisted balloon inflation to keep the patency of both PCAs. This technique is more beneficial for reducing the risk of stent deformity than Y-stenting, and it provides a simpler procedure than other advanced stent techniques. Additionally, it enables an easy approach when retreatment is necessary for aneurysm recurrence. This technique may be one of the useful procedures for embolizing broad-necked basilar terminal aneurysms safely and effectively.


Scours in pigs.


COVID-19-the frontline (a GP perspective).


title: Scanning electron microscopic characterization of bovine coronavirus plaques in HRT cells.

text: The ecology of cytopathic expression of bovine coronavirus (BCV) in HRT-18 cells was analyzed within virus-induced plaques by scanning electron microscopy. Virus replication was cytocidal for many HRT-18 cells, a function enhanced in the presence of trypsin. A monolayer of cells remained that imparted a characteristic turbidity to the plaque. These structurally normal, lysis-resistant cells did not stain with fluorescent antibodies specific for BCV antigens, failed to adsorb virus particles or mouse erythrocytes in contrast to the susceptible cells. The survival of cells in the plaque interior reflects a non-productively infected population with evidence of viral persistence.


title: Laparoscopic resection of hepatocellular carcinoma. Considerations on lesions in the posterosuperior segments of the liver.

text: AIM The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR) of hepatocellular carcinoma (HCC) including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. MATERIAL OF STUDY Between June 2005 and May 2009, we performed 22 LLR for HCC. The underlying cirrhosis was staged as Child A in 19 cases and Child B in 3. RESULTS LLR included a non anatomic resection in 15 cases and an anatomic resection in 7. A conversion to laparotomy occurred in one (4.5%) patient for hemorrhage. Mortality and morbidity rates were 0% and 18.1% (4/20). Over a mean follow-up period of 29 months (range: 19-65 months), 11 (50%) patients presented recurrence, mainly at distance from the surgical site. DISCUSSION A laparoscopic approach is more suitable when the lesion is located in the peripheral "laparoscopic" segments 2 to 6. Nevertheless, six resections were made in the posterosuperior segments. Although parenchymal-sparing resection is required by the presence of underlying liver disease, anatomic resection has always to be considered and pursued to reduce local recurrence. In our series the recurrence rate was similar to those reported for other laparoscopic studies and for open resection of HCC. CONCLUSIONS LLR for HCC in selected patients is a safe procedure with good short-term results. It can also be proposed in tumor locations with a difficult surgical access maintaining a low morbidity rate and good oncologic adequacy. This approach could have an impact on the therapeutic strategy of HCC complicating cirrhosis as a treatment with curative intent or as a bridge to liver transplantation.


title: Multiple-serotype Salmonella gastroenteritis outbreak after a reception --- Connecticut, 2009.

text: In September 2009, the Connecticut Department of Public Health (DPH) identified an outbreak of Salmonella gastroenteritis among attendees at a reception. A case-control study and environmental and laboratory investigations were conducted. Nine case-patients and 14 control subjects were identified. Potato salad consumption was strongly associated with illness (odds ratio [OR] = 84.0). During the investigation, food service workers were observed to have bare-handed contact with ready-to-eat food. Five case-patients and one asymptomatic food service worker had stool samples positive for Salmonella species. Two Salmonella serotypes were identified, Salmonella enterica serovar Schwarzengrund and Salmonella enterica serovar Typhimurium variant O:5--, including coinfection in one case-patient and one food service worker. The isolates of each respective serotype (S. Schwarzengrund and S. Typhimurium variant O:5--) had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. Potato salad was the likely source of the outbreak but the contamination mechanism is unclear. Control measures included exclusion of the food service worker with Salmonella-positive stool from the restaurant until two consecutive stool samples yielded no bacterial growth. Standard public health laboratory practices in Connecticut and testing techniques used specifically during this investigation led to the rapid identification of the two serotypes. Multiple-serotype Salmonella outbreaks might occur more frequently than recognized; knowledge of all Salmonella serotypes involved in an outbreak might help implicate the outbreak source, define the scope of the outbreak, and determine the selection of appropriate control measures.


title: Generation of a replication-competent, propagation-deficient virus vector based on the transmissible gastroenteritis coronavirus genome.

text: Replication-competent propagation-deficient virus vectors based on the transmissible gastroenteritis coronavirus (TGEV) genome that are deficient in the essential E gene have been developed by complementation within E(+) packaging cell lines. Cell lines expressing the TGEV E protein were established using the noncytopathic Sindbis virus replicon pSINrep21. In addition, cell lines stably expressing the E gene under the CMV promoter have been developed. The Sindbis replicon vector and the ectopic TGEV E protein did not interfere with the rescue of infectious TGEV from full-length cDNA. Recombinant TGEV deficient in the nonessential 3a and 3b genes and the essential E gene (rTGEV-Delta3abDeltaE) was successfully rescued in these cell lines. rTGEV-Delta3abDeltaE reached high titers (10(7) PFU/ml) in baby hamster kidney cells expressing porcine aminopeptidase N (BHK-pAPN), the cellular receptor for TGEV, using Sindbis replicon and reached titers up to 5 x 10(5) PFU/ml in cells stably expressing E protein under the control of the CMV promoter. The virus titers were proportional to the E protein expression level. The rTGEV-Delta3abDeltaE virions produced in the packaging cell line showed the same morphology and stability under different pHs and temperatures as virus derived from the full-length rTGEV genome, although a delay in virus assembly was observed by electron microscopy and virus titration in the complementation system in relation to the wild-type virus. These viruses were stably grown for >10 passages in the E(+) packaging cell lines. The availability of packaging cell lines will significantly facilitate the production of safe TGEV-derived vectors for vaccination and possibly gene therapy.


title: Field trial evaluation of a reo-coronavirus calf diarrhea vaccine.

text: Field trials were conducted using an experimental, modified live virus, oral vaccine for prevention of reo- and coronavirus calf diarrhea. Prior to the trials, one or both of the specific causative agents were identified from affected calves in each participating herd. In 21 herds, sequential trials were conducted in which results of uninterrupted vaccination were compared with disease rates during a preceding or subsequent control period. In these herds there was a statistically significant reduction in the morbidity and mortality from disease in 1,598 vaccinates compared with the rates in 829 prevaccination control calves. Morbidity and mortality in 206 post-vaccination control calves rose marginally above the rates in the same vaccinates. In 26 other herds, where double blind trials were conducted, rates of morbidity and mortality from disease were virtually the same for 1,080 vaccinated calves and 355 placebo calves. Vaccinates in the sequential trials had the lowest morbidity and mortality rates of any test group in either field trial format. In a selected dairy herd, both field trial formats were implemented and the results compared. In the double blind trial, vaccinates and placebo calves had comparable rates of morbidity and mortality from disease. When a sequential trial was later implemented, a statistically significant reduction in morbidity and mortality occurred in vaccinates compared with rates in control calves.


COVID-19 and Remdesivir, Insulin Analogues, Opioid Use Disorder, Urinary Incontinence.


docid: utfyyuks

title: Tissue distribution of avian infectious bronchitis virus following in ovo inoculation of chicken embryos examined by in situ hybridization with antisense digoxigenin-labeled universal riboprobe.

text: Chicken embryos were inoculated with 8 different strains of infectious bronchitis virus (IBV) representing 7 different serotypes at 17 days of embryonation. At 2 and 5 days postinfection (dpi), tissues were collected for in situ hybridization using an antisense digoxigenin-labeled riboprobe corresponding to the sequence of the mRNA coding for the membrane protein. Extensive antigen staining in the cytoplasm of epithelial cells in the trachea, lung, bursa, and intestine was detected at 2 dpi with all 8 strains of IBV. At 5 dpi, little or no positive staining was observed in these tissues. However, tubular cells of the kidney showed multifocal positive staining with the Wolgemuth strain-, Gray strain-, JMK strain-, and Mass41 strain-infected chickens. No viral RNA was detected in the spleen at any time point. The results demonstrated strict epitheliotropic nature and wide tissue tropism of strains of IBV in the chicken embryo and the universality of our riboprobe. In situ hybridization with this probe will be useful for understanding the tissue tropism and the pathogenesis of IBV in vivo.


title: [Comparison on the performance of both temporal and temporal-spatial models for outbreak detection through China Infectious Diseases Automated-alert and Response System (CIDARS)].

text: OBJECTIVE To analyze the pilot results of both temporal and temporal-spatial models in outbreaks detection in China Infectious Diseases Automated-alert and Response System (CIDARS) to further improve the system. METHODS The amount of signal, sensitivity, false alarm rate and time to detection regarding these two models of CIDARS, were analyzed from December 6, 2009 to December 5, 2010 in 221 pilot counties of 20 provinces. RESULTS The sensitivity of these two models was equal (both 98.15%). However, when comparing to the temporal model, the temporal-spatial model had a 59.86% reduction on the signals (15 702) while the false alarm rate of the temporal-spatial model (0.73%) was lower than the temporal model (1.79%), and the time to detection of the temporal-spatial model (0 day) was also 1 day shorter than the temporal model. CONCLUSION Comparing to the temporal model, the temporal-spatial model of CIDARS seemed to be better performed on outbreak detection.


title: Poliovirus induces Bax-dependent cell death mediated by c-Jun NH2-terminal kinase.

text: Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome c release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member of the Bcl-2 family; this activation involves its conformational change and its redistribution from the cytosol to mitochondria. Neutralization of Bax by vMIA protein expression prevents cytochrome c release, consistent with a contribution of PV-induced Bax activation to mitochondrial outer membrane permeabilization. Interestingly, we also found that c-Jun NH(2)-terminal kinase (JNK) is activated soon after PV infection and that the PV-cell receptor interaction alone is sufficient to induce JNK activation. Moreover, the pharmacological inhibition of JNK by SP600125 inhibits Bax activation and cytochrome c release. This is, to our knowledge, the first demonstration of JNK-mediated Bax-dependent apoptosis in PV-infected cells. Our findings contribute to our understanding of poliomyelitis pathogenesis at the cellular level.


[Betydningen af COVID-19 i forbindelse med kirurgi].


title: Mechanical Thrombectomy Using Solitaire in a 6-Year-Old Child.

text: A six-year-old boy was diagnosed as recurrent posterior circulation stroke secondary to basilar artery occlusion with rapid progression of symptoms. Etiology of stroke was a dissection of V3 segment of left vertebral artery, which was treated using endovascular technique 26 hours after worsening of symptoms. Since the guidelines for acute revascularization in pediatric stroke are not well established, there is limited experience in the use of mechanical devices for acute ischemic stroke revascularization in children. To our knowledge, this is one of the youngest reported cases of acute ischemic stroke from Asia managed with newer mechanical clot removal devices.


title: Coronavirus Disease (COVID-19) and the Gastrointestinal System in Children.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), though primarily a respiratory pathogen, also involves the gastrointestinal tract. Similar to the respiratory mucosa, angiotensin converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 TMPRSS2) co-express in the gastrointestinal tract, which facilitates viral entry into the tissue. Less than 10% of children with infection develop diarrhea and vomiting. Prolonged RT PCR positivity in the stool has raised the possibility of feco-oral transmission. Elevated transaminases are common, especially in those with severe coronavirus disease-2019 (COVID -19) disease. Children with inflammatory bowel disease and post liver transplant patients do not have an increased risk of disease, and should remain on medications they are already on. Children with chronic liver disease should continue their medications as usual. All elective procedures like endoscopy should be postponed.


title: Mental Health Act 1983.

text: After reviewing the history of mental health legislation in England, Hamilton discusses some provisions of the new Mental Health Act that went into effect in September 1983. Among the issues pertaining to involuntary commitment covered by the act are the terminology and definition of mental illness; criteria for emergency admission, admission for assessment, and length of detention; patients' rights; mental health review tribunals; and consent to treatment. Two of the more controversial provisions are the reinstitution of a mental health commission with protective functions for detained patients, and a mandatory second opinion for certain forms of treatment.


title: Characterization of phage-displayed recombinant anti-idiotypic antibody fragments against coronavirus-neutralizing monoclonal antibodies.

text: Murine coronaviruses provide useful animal models for human neurological disorders such as multiple sclerosis. In an effort to better understand the mechanisms involved in protection from coronavirus infection, we are studying the role of the idiotypic network in the modulation of viral infectivity. We have explored the feasibility of using single-chain antibodies displayed on phage surfaces for the isolation of recombinant anti-idiotypic antibodies (anti-Ids) with antigen-mimicking properties, which has proven to be difficult with conventional hybridoma approaches. A phage-display library containing more than 10(8) different antibody specificities was screened for the presence of anti-Ids by successive rounds of panning with three different in vitro neutralizing and in vivo protective antiviral monoclonal antibodies. After five rounds of panning, between 32% and 84% of all individual clones tested showed antibody-binding in an enzyme-linked immunosorbent assay (ELISA). Although several clones showed identical antibody sequences, a number of different clones were identified and further characterized. None of the selected clones induced the production of antiviral or neutralizing antibodies or conferred reproducible protection from viral challenge in BALB/c and C57BL/6 mice. These results demonstrate that anti-Ids can be isolated from a phage-display library, although high-affinity antigen-mimicking phages with antiviral protective capacities were apparently not represented in this library. This argues for the development of more diverse phage-display libraries.


title: Newly Diagnosed Glomerulonephritis During COVID-19 Infection Undergoing Immunosuppression Therapy, a Case Report.

text: During the COVID-19 pandemic, we had a 25 years old male case without any underlying disease or history of autoimmune disease in COVID-19 Clinic, Isfahan, Iran. He presented with arthralgia and weakness so we started COVID-19 therapeutic regimen. In his hospitalization, creatinine increases and abnormalities in random urine sediment was seen. Methylprednisolone and cyclophosphamide were prescribed due to suspected glomerulonephritis. After renal biopsy the diagnose was confirmed as crescentic proliferative glomerulonephritis. The patient also, underwent plasmapheresis and intravenous immunoglobulin injection. He was discharged healthy without development of new pulmonary symptoms despite immunosuppressive treatment.


title: Equipment, supplies, and pharmaceuticals: how much might it cost to achieve basic surge capacity?

text: The ability to deliver optimal medical care in the setting of a disaster event, regardless of its cause, will in large part be contingent on an immediately available supply of key medical equipment, supplies, and pharmaceuticals. Although the Department of Health and Human Services Strategic National Stockpile program makes these available through its 12-hour "push packs" and vendor-managed inventory, every local community should be funded to create a local cache for these items. This report explores the funding requirements for this suggested approach. Furthermore, the response to a surge in demand for care will be contingent on keeping available staff close to the hospitals for a sustained period. A proposal for accomplishing this, with associated costs, is discussed as well.


title: [Dynamic changes of T lymphocyte subsets in the long-term follow-up of severe acute respiratory syndrome patients].

text: OBJECTIVE To study the dynamic changes of T lymphocyte subsets in severe acute respiratory syndrome (SARS) patients. METHODS Sequential anti-coagulated blood samples were collected from 62 seropositive SARS patients during the first week, the second week, the first month, the 2nd-3rd month, and 1 year after disease onset. T-lymphocyte subsets including CD4 + T cells, CD8 + T cells, and naive and memory CD4 + T cells were detected by flow cytometry. Samples from 56 healthy blood donors were also detected as healthy controls. RESULTS A rapid restoration in T-lymphocyte subsets was observed during a short period after infection. During the 2-3 months after disease onset, CD8 + T cell count returned to the normal level. At the same time point, CD4 + T cell and naive CD4 + T cell counts increased to (534 +/- 197)/mm3 and (175 +/- 75)/mm3 respectively. Total lymphocytes, T lymphocyte, CD4 + T and naive CD4 + T cell were still significantly lower than the normal levels even one year after disease onset. CONCLUSION The periphery T lymphocyte subsets in SARS infection shows transient decrease and then rapid recovery.


title: Vaccination against lethal coronavirus-induced encephalitis with a synthetic decapeptide homologous to a domain in the predicted peplomer stalk.

text: A surface probability method was used to select a decapeptide homologous to residues 993 to 1002 of the peplomer protein E2 of murine hepatitis virus strain JHM, a neurotropic coronavirus. This sequence of amino acids corresponded to a minor peak on a hydrophilicity plot. Immunization of mice with the chemically synthesized peptide coupled to keyhole limpet hemocyanin elicited high levels of neutralizing antibody and protected against lethal virus challenge. Protection correlated with a critical level of antipeptide antibody, which could be reached after a single inoculation. These results suggest that an appropriate antibody response to a highly restricted, surface-exposed domain of this viral protein is critical in determining the outcome of infection of the central nervous system. This sequence is located in the C-terminal fifth of the E2 peplomers, between two predicted coiled-coil structures.


title: The Internet's impact on the practice of psychiatry.

text: OBJECTIVE In the past decade, the Internet has rapidly evolved into a mainstream communication and information resource. During this period, health care resources and databases have been developed. This paper reviews the literature on e-mail communication and on-line health care information resources to determine the impact on psychiatry. METHOD The Medline electronic database and the search engines Altavista and Google were used to review the literature discussing on-line guidelines, clinical trials, and continuing medical education (CME) resources, as well as the literature on Internet usage, e-journals, and e-mail communication. CONCLUSIONS The Internet has accelerated psychiatrists' access to new research findings and other information pertinent to clinical practice. It has eliminated distance barriers and offered psychiatrists and the general public equal access to scientific articles, clinical trials, and guidelines. The literature shows that the general public is using the Internet to obtain information and, to a lesser extent, to communicate with health care professionals. In terms of health outcomes, the effectiveness of patient on-line access to information is still uncertain, and further research is necessary. Although physicians have embraced on-line journals, further work is required before they embrace on-line CME. The Internet has developed to a point where it is important for psychiatrists to understand the issues and pitfalls in its use, to be able to access the resources available, and to be in a position to mentor patients who want to research their condition further.


title: [Diagnostic algorithm for COVID-19 at the ER].

text: OBJECTIVE Evaluation of a diagnostic algorithm for estimating the risk of COVID-19 in patients who are referred to an emergency department for being suspected of having the disease. DESIGN Retrospective study. METHOD Patients with fever with no apparent cause and patients with recently developed respiratory symptoms, whether or not in combination with fever, were routinely given a PCR test, blood tests (lymphocyte count and LDH levels) and a chest CT scan. The CT scan was assessed according to the CO-RADS classification. Based on the findings, the patients were divided into 3 cohorts (proven COVID-19, strong suspicion of COVID-19, and low suspicion of COVID-19) and the appropriate isolation measures were taken. RESULTS In the period from 8 to 31 March 2020, the algorithm was applied to 312 patients. COVID-19 was proven for 69 (22%) patients. COVID-19 was strongly suspected for 151 (48%) patients and suspicion was low for the remaining 92 (29%) patients. The percentage of patients with positive PCR results and the percentage of patients with abnormal laboratory test results increased as the CO-RADS score increased. Among patients with a CO-RADS score of 4 or 5, this percentage increased further when they also had lymphopenia or elevated LDH levels. We have adjusted the flowchart based on our findings. CONCLUSION In case of patients who have been referred to an emergency department for suspected COVID-19, a good COVID-19 risk assessment can be made on the basis of clinical signs, laboratory abnormalities and low-dose CT scans. Even before the results of the PCR test are known and even if the results are negative, patients can be classified as 'proven COVID-19 patients' using the algorithm.


title: Adjustment outcomes in Chinese patients following one-month recovery from severe acute respiratory syndrome in Hong Kong.

text: This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.


title: Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial.

text: BACKGROUND Echinacea purpurea stimulates the immune response and is promoted to reduce symptom severity and the duration of upper respiratory tract infections. We sought to determine the efficacy of a standardized preparation of E purpurea in reducing symptom severity and duration of the common cold. METHODS A randomized, double-blind, placebo-controlled design was used. Patients received either 100 mg of E purpurea (freeze-dried pressed juice from the aerial portion of the plant) or a lactose placebo 3 times daily until cold symptoms were relieved or until the end of 14 days, whichever came first. Symptoms (sneezing, nasal discharge, nasal congestion, headache, sore or scratchy throat, hoarseness, muscle aches, and cough) were scored subjectively by the patient and recorded daily in a diary. Kaplan-Meier curves were used to estimate the survival function of time to resolution in each group. The Wilcoxon rank sum test was used to compare time to resolution between the 2 groups. RESULTS One hundred twenty-eight patients were enrolled within 24 hours of cold symptom onset. Group demographic distribution was comparable for sex, age, time from symptom onset to enrollment in the study, average number of colds per year, and smoking history. No statistically significant difference was observed between treatment groups for either total symptom scores (P range,.29-.90) or mean individual symptom scores (P range,.09-.93). The time to resolution of symptoms was not statistically different (P =.73). CONCLUSIONS Some studies have concluded that Echinacea effectively reduces the symptoms and duration of the common cold. We were unable to replicate such findings. Further studies using different preparations and dosages of E purpurea are necessary to validate previous claims.


title: The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma.

text: The solvent/detergent (SD) process used for plasma can safely inactivate all lipid-enveloped viruses. The introduction of a specific prion-binding ligand gel in combination with SD treatment, time-reduced from 4 to 1-1.5 h, still ensures efficient virus kill, reduces abnormal prion protein by >5 log steps, and preserves levels of plasmin inhibitor at close to the reference range. Infections with known non-enveloped viruses such as HAV or parvovirus B19 are prevented by ensuring low virus loads in the starting plasma units, dilution through pooling of single plasma units, and neutralization of immune antibodies already present in the initial plasma pools. The major advantages of SD plasma over fresh frozen plasma and the other pathogen-inactivated plasmas are its extreme safety with respect to transfusion-related acute lung injury and the significantly lower likelihood of provoking allergic reactions. Both advantages are best interpreted as results of the dilution effect of pooling. No fewer than 18 clinical studies covering all indications for plasma, and extensive clinical experience have shown that reduced levels of coagulation factors and inhibitors as a result of SD treatment do not impair significantly the clinical efficacy or tolerance of plasma. Properly standardized clotting factor and inhibitor potencies and low batch-to-batch variations when compared with single-donor plasma units makes SD plasma more suitable for standardized treatment.


title: Pathological studies on encephalitis in mice experimentally inoculated with bovine coronavirus.

text: One- to 21-day-old mice were examined pathologically after inoculated intracerebrally or subcutaneously with the Kakegawa strain of bovine coronavirus. In 1- to 4-day-old mice inoculated intracerebrally, the brain contained a small number of neutrophils and lymphocytes having infiltrated diffusely and perivascularly and some degenerative neurons. In mice inoculated intracerebrally at 7 to 21 days of age, severe necrosis of pyramidal cells was shown in Ammon's horn. Perivascular infiltrations of neutrophils and lymphocytes were moderate to severe. Some neurons were degenerative in the cerebral cortex, thalamus and midbrain. Degeneration of some neurons and mild infiltration of neutrophils and lymphocytes were observed in the brain of mice inoculated subcutaneously at 1 to 7 days of age. Perivascular infiltration of neutrophils and lymphocytes was prominent in the cerebral cortex of mice inoculated subcutaneously at 14 days of age. Cellular infiltration was also seen in the thalamus, Ammon's horn, midbrain, cerebellum and medulla oblongata. All the mice, except one, inoculated subcutaneously at 21 days of age were free from neural changes. Electron-microscopically, virus particles were observed in and outside of the degenerative neurons. They had a core 70 nm in diameter and an envelope with spikes.


title: Redistribution and reduction of interphotoreceptor retinoid-binding protein during ocular coronavirus infection.

text: Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravitreal inoculation) was examined on interphotoreceptor retinoid-binding protein (IRBP), the glycolipoprotein in the interphotoreceptor matrix (IPM) thought to transport retinoids between the photoreceptors and the RPE. Changes in IRBP distribution accompanied virus-associated retinal pathology, including photoreceptor loss and RPE abnormalities. Immunohistochemistry on days 3 and 6 showed that IRBP had diffused into the neural retina away from the IPM. The IRBP became localized abnormally in the same areas as virus-induced lesions, shown by staining adjacent sections with a monoclonal antibody specific for the viral nucleocapsid protein. Moreover, the level of IRBP in isolated retinas, measured in an immunoslot-blot assay, decreased significantly by day 3 and remained low through day 23. This decrease was confirmed in eyecups isolated on day 6. It may be caused in part by loss of photoreceptors and diffusion of IRBP through the retina into the vitreous. These studies show that a virus may induce an acute, limited infection in the retina that can be cleared by the host. However, the infection initiated a series of events resulting in long-term reduction and redistribution of a critical photoreceptor protein.


title: Production of an anti-severe acute respiratory syndrome (SARS) coronavirus human monoclonal antibody Fab fragment by using a combinatorial immunoglobulin gene library derived from patients who recovered from SARS.

text: A combinatorial human immunoglobulin gene library was constructed from the peripheral lymphocytes of two patients who recovered from severe acute respiratory syndrome (SARS). The library was screened for the production of Fab antibody fragments to a recombinant spike protein of SARS-associated coronavirus (SARS-CoV). One Fab clone, AS3-3, reacted with the spike protein in an enzyme-linked immunosorbent assay. The dissociation constant of AS3-3 was 1.98 x 10(-8) M. Immunofluorescent microscopy revealed that it reacted with SARS-CoV-infected cells. The library seems to be a potent tool for the production of human antibodies to SARS-CoV.


title: Methylmercury induces pancreatic beta-cell apoptosis and dysfunction.

text: Mercury is a well-known toxic metal, which induces oxidative stress. Pancreatic beta-cells are vulnerable to oxidative stress. The pathophysiological effect of mercury on the function of pancreatic beta-cells remains unclear. The present study was designed to investigate the effects of methylmercury (MeHg)-induced oxidative stress on the cell viability and function of pancreatic beta-cells. The number of viable cells was reduced 24 h after MeHg treatment in a dose-dependent manner with a range from 1 to 20 microM. 2',7'-Dichlorofluorescein fluorescence as an indicator of reactive oxygen species (ROS) formation after exposure of HIT-T15 cells or isolated mouse pancreatic islets to MeHg significantly increased ROS levels. MeHg could also suppress insulin secretion in HIT-T15 cells and isolated mouse pancreatic islets. After 24 h of exposure to MeHg, HIT-T15 cells had a significant increase in mercury levels with a dose-dependent manner. Moreover, MeHg displayed several features of cell apoptosis including an increase of the sub-G1 population and annexin-V binding. Treatment of HIT-T15 cells with MeHg resulted in disruption of the mitochondrial membrane potential and release of cytochrome c from the mitochondria to the cytosol and activation of caspase-3. Antioxidant N-acetylcysteine effectively reversed the MeHg-induced cellular responses. Altogether, our data clearly indicate that MeHg-induced oxidative stress causes pancreatic beta-cell apoptosis and dysfunction.


title: Glycopeptides in clinical development: pharmacological profile and clinical perspectives.

text: Vancomycin and teicoplanin are the two glycopeptides currently used in the clinics for the treatment of multiresistant infections by Gram-positive organisms. The development of resistance in enterococci and staphylococci has stimulated the search for new derivatives with improved activity, particularly against strains resistant to conventional derivatives. Three of these, obtained by hemi-synthesis starting from natural compounds, are now in clinical development (oritavancin and telavancin, as derivatives of vancomycin; and dalbavancin, as a derivative of teicoplanin). The presence of a lipophilic tail on these molecules results in them having a prolonged half-life. It also modifies their mode of action, conferring to them a concentration-dependent bactericidal activity. Their spectrum of activity includes methicillin-susceptible or methicillin-resistant staphylococci, penicillin-resistant pneumococci and enterococci (including vancomycin-resistant strains for oritavancin and telavancin). Ongoing clinical studies are evaluating the efficacy and safety of these molecules for the treatment of complicated skin and soft tissue infections and bactereamia, in a once-daily (oritavancin, telavancin) or once-weekly (dalbavancin) scheme of administration. Despite these remarkable properties, the use of these potent molecules should be restricted to severe infections by multiresistant organisms to limit the risk of selection of resistance.


title: Newcastle disease virus may enter cells by caveolae-mediated endocytosis.

text: The entry into cells of Newcastle disease virus (NDV), a prototype member of the paramyxoviruses, is believed to occur by direct fusion at the plasma membrane through a pH-independent mechanism. In addition, NDV may enter host cells by an endocytic pathway. Treatment of cells with drugs that block caveolae-dependent endocytosis reduced NDV fusion and infectivity, the degree of inhibition being dependent on virus concentration. The inhibitory effect was reduced greatly when drugs were added after virus adsorption. Cells treated with methyl beta-cyclodextrin, a drug that sequesters cholesterol from membranes, reduced the extent of fusion, infectivity and virus-cell binding; this indicates that cholesterol plays a role in NDV entry. Double-labelling immunofluorescence assays performed with anti-NDV monoclonal antibodies and antibodies against the early endosome marker EEA1 revealed the localization of the virus in these intracellular structures. Using fluorescence microscopy, it was found that cell-cell fusion was enhanced at low pH. It is concluded that NDV may infect cells through a caveolae-dependent endocytic pathway, suggesting that this pathway could be an alternative route for virus entry into cells.


title: Panzootics and the poor: devising a global livestock disease prioritisation framework for poverty alleviation.

text: Panzootics such as highly pathogenic avian influenza and Rift Valley fever have originated from the South, largely among poor communities. On a global level, approximately two-thirds of those individuals living on less than US$2 per day keep livestock. Consequently, there is a need to better target animal health interventions for poverty reduction using an evidence-based approach. Therefore, the paper offers a three-step prioritisation framework using calculations derived from standard poverty measures: the poverty gap and the head count ratio. Data from 265 poor livestock-keeping households in Kenya informed the study. The results demonstrate that, across a spectrum of producers, the dependence upon particular species varies. Furthermore, the same livestock disease has differing impacts on the depth and severity of poverty. Consequently, animal health interventions need to account for variability in income effects at the species and disease levels.