title: Cardiovascular pathology possibly associated with ketamine/xylazine anesthesia in Dutch belted rabbits.

text: BACKGROUND AND PURPOSE After myocardial necrosis and fibrosis was observed in five rabbits which had been anesthetized a variable number of times, the potential relationship of these lesions and anesthesia was evaluated in 35 other rabbits. METHODS Anesthesia was induced by intramuscular administration of ketamine and xylazine followed by infusion of lactated Ringer's solution also containing ketamine and xylazine. Group A rabbits (n = 9) were subjected to multiple anesthesias and were evaluated by echocardiography, thoracic radiography, electrocardiography, determination of serum coronavirus titer, vitamin E concentration, and complete necropsy. Prior to a single acute procedure followed by necropsy, group B rabbits (n = 11) were evaluated by echocardiography only. Group C rabbits (n = 10) had never been anesthetized and were necropsied after euthanasia. Group D rabbits (n = 5) had intermediate anesthesia exposure history and were evaluated by echocardiography only. Myocardial fibrosis was scored semi-quantitatively on a scale of 0 to 4. RESULTS Canine coronavirus test results were negative; hypovitaminosis E was evident, and fibrosis scores were significantly increased in group A, compared with group B or group C, rabbits. CONCLUSION Etiologic differentials included alpha2-agonist-mediated coronary vasoconstriction with associated myocardial hypoperfusion, hypovitaminosis E and free radical injury, and other anesthetic-induced physiologic trespass.


title: Phosphatidyl-serine inhibition of OC43 and NCDCV coronavirus infectivity.

text: Human OC43 and bovine neonatal calf diarrhoea coronavirus (NCDCV) are known to be inhibited by non-antibody factors present in sera of different mammalian species, including man and cattle. Such an inhibitor is also present in fetal calf serum generally used for growing and maintaining cell cultures, thus influencing the viral infectivity titer. Previous reports refer to the effectiveness of phospholipase C treatment in eliminating the inhibiting activity. In order to detect the compound possibly involved in coronavirus growth inhibition (among the phospholipids naturally present in mammalian sera), we tested several phospholipids with hemagglutino-inhibition test and plaque reduction assay. Only phosphatidyl-serine seemed to be effective on Coronavirus OC43 and NCDCV, as detected by plaque-reduction assay, but not by hemagglutino-inhibition test.


title: Development and validation of an enzyme-linked immunosorbent assay for human metapneumovirus serology based on a recombinant viral protein.

text: The human metapneumovirus (hMPV) is a newly reported respiratory virus belonging to the Paramyxoviridae family that has been associated with bronchiolitis and pneumonia in young children. We developed a simple enzyme-linked immunosorbent assay (ELISA) for hMPV serological testing using the nucleoprotein (N) from group A or B (N-A or N-B) as the antigen, and we evaluated it in both children and adults. The N proteins were first used in a Western immunoblot assay to identify hMPV-negative sera, which were then used to determine the cutoff value of the ELISA test. Subsequent evaluation of the ELISA-N test revealed that the mean reciprocal antibody titer of 20 randomly selected seropositive children was 143, compared to 69 for 20 seropositive adults. In a prospective evaluation of 71 adults with acute exacerbations of chronic obstructive pulmonary disease, 58 (81.6%) had prior hMPV antibodies and 3 (4.2%) had evidence of recent hMPV infection. In testing paired sera from adults (n = 4) with recent hMPV group A infection confirmed by reverse transcriptase PCR (RT-PCR), ELISAs using the N-A or N-B proteins were able to detect hMPV seroconversion. Moreover, testing of paired sera from three adults with a recent infection by the human respiratory syncytial virus confirmed by RT-PCR and serology did not reveal any increase in hMPV antibodies over time. The ELISA-N is a simple, objective, and specific serological test useful for detecting anti-hMPV antibodies following group A or B viral infections, which should permit a better understanding of the epidemiology of this virus.


title: Evidence for differential roles for NKG2D receptor signaling in innate host defense against coronavirus-induced neurological and liver disease.

text: Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-gamma) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-gamma production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-gamma expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-gamma and tumor necrosis factor alpha secretion.


title: Marginal ulcer after Roux-en-Y gastric bypass: what have we really learned?

text: BACKGROUND The definition of marginal ulcer after Roux-en-Y gastric bypass (RYGB) is widely debated. This study reviewed findings of upper endoscopy in symptomatic patients at a quaternary bariatric referral center. Further investigation included symptom constellation, potential etiologies, and efficacy of treatment for patients found to have marginal ulcer. METHODS Patients presenting for upper gastrointestinal endoscopy after Roux-en-Y gastric bypass were included in this study. An institutional review board-approved database was queried for the period 1 June 2010 to 31 August 2011. Subgroup analysis was performed for patients with marginal ulcer. Statistical analysis was performed using PASW version 18 for Windows. RESULTS During the study period, 455 upper gastrointestinal endoscopies were performed for 328 consecutive symptomatic patients. Marginal ulcer, found in 112 patients (34 %), was diagnosed for 59 of the patients (53 %) within 12 months after surgery and for 53 of the patients (47 %) more than 12 months after surgery. In patients found to have marginal ulcer, the most common presenting symptoms were pain, dysphagia, nausea, and vomiting. All the patients with marginal ulcer underwent acid suppression and cytoprotective therapy. Using uni- and multivariate analyses for healing, nonhealing, and healing with recurrence, tobacco use was found to be the solitary significant risk factor for recurrence (p = 0.01). CONCLUSION Patients with pain or dysphagia after gastric bypass warrant upper endoscopy given the high yield for abnormalities. Although the risk factors for the development of marginal ulcer remain multifactorial, a thorough investigation for potential etiologies including tobacco, alcohol, and nonsteroidal antiinflammatory drug (NSAID) usage should be determined and eliminated. The presence of multiple risk factors may pose a higher challenge in ulcer resolution, leading to increased recurrence. In the current series, prior or current tobacco use remained the sole independent risk factor for ulcer persistence.


title: [Ethical principles compromised during the COVID-19 pandemic?]

text: In the late 1970s, the American bioethicists Tom Beauchamp and James Childress described the four ethical principles that should guide a physician's actions in individual patient care. These principles are: (a) respect for autonomy; (b) doing well (beneficence); (c) not harming (non-maleficence); and (d) justice. In many countries, the global outbreak of SARS-CoV-2 has led to overloaded healthcare systems due to large numbers of COVID-19 patients. In order to provide care to this high volume of patients, far-reaching measures are taken that affect everyone. These measures are not taken from an individual patient's perspective but in the interest of public health; nonetheless, they can directly affect the individual patient's interests. This article examines the extent to which Beauchamp and Childress' ethical principles may be compromised during the COVID-19 pandemic.


title: Evaluating mutant mice: anatomic pathology.

text: As the human and mouse genome projects approach their goals, initiatives in functional genomics are advancing. When the nucleotide sequences are available, identification of gene functions will assume even greater importance. Determination of gene products and their proximal biochemical functions provide a part of the picture, but determination of their functions in the context of the whole organism is the ultimate goal. The manipulated mouse genome has become accepted as a model for understanding the genetic basis of human conditions and diseases. Consequently, biomedical research institutions have seen significant increases in the use of mice since the early 1980s, and these increases are largely attributable to the use of genetically modified mice. The role of comparative pathology in research on mutant mouse models of disease is increasing in response to these trends. Evaluation and phenotypic characterization of mutant mice, via clinical and anatomic pathology techniques, will be an important component of functional genomics initiatives.


Daily Situation Report on Coronavirus disease (COVID-19) in Iran; March 13, 2020.


title: Tissue ingrowth into foam but not into gauze during negative pressure wound therapy.

text: UNLABELLED   Background. Foam and gauze are two types of wound fillers used for negative pressure wound therapy (NPWT). Differences in the wound healing effects of foam and gauze have been observed clinically. The aim of the present study was to examine the effects of NPWT on the wound bed using foam and gauze. METHODS A porcine peripheral wound model was treated with NPWT at 0, -75 mmHg, or -125 mmHg for 72 hours. The effects of foam and gauze on the wound bed were compared, and the force required to remove the dressings was measured. Sections of biopsies from the wound bed with an overlying dressing were stained with hematoxylin-eosin and Giemsa and were examined histologically. RESULTS The force ratio needed to remove the wound filler from the wound bed after treatment with negative pressure was greater for foam than for gauze. NPWT caused the wound bed tissue to grow into the foam, while there was no such ingrowth into gauze. Furthermore, beneath the foam there was more leukocyte infiltration, tissue disorganization, disruption of contact among cells, and differences in size among cells. The results were similar regardless of the level of negative pressure. CONCLUSION More force was required to remove foam compared to gauze following NPWT, which may have been due to greater ingrowth into foam. These findings may explain the patient discomfort and wound bed disruption upon removal of foam. The observed differences in wound bed tissue morphology under foam and gauze are in accordance with the clinically observed differences in quality of granulation tissue formation.


title: Vertical transmission of gill-associated virus (GAV) in the black tiger prawn Penaeus monodon.

text: Chronic gill-associated virus (GAV) infection is endemic in Penaeus monodon broodstock captured from north-east Queensland in Australia and in farmed shrimp produced from these. We investigated the role of vertical transmission in perpetuating the high prevalence of these chronic GAV infections. Reverse transcription (RT)-nested PCR detected GAV in spermatophores and mature ovarian tissue from broodstock and in fertilized eggs and nauplii spawned from wild-fertilized females. In laboratory-reared P. monodon (> 12 mo old) that had a high mortality rate, RT-nested PCR detected GAV in male spermatophores at levels significantly higher than that detected in the lymphoid organ. By transmission electron microscopy (TEM), GAV virions were detected in spermatophore seminal fluid, but not sperm cells. Histological evidence of hypertrophied cell foci (spheroids) and TEM observation of GAV nucleocapsids and virions in spheroid cells was also found in 100% of lymphoid organs of approximately 1.2 g juvenile P. monodon reared in the laboratory from postlarvae collected from commercial hatcheries. Sequence analysis of PCR amplicons from parental P. monodon and fertilized eggs of artificially inseminated broodstock indicated that GAV associated with eggs can originate from both the male and female parents. Although the female GAV genotype was predominant in eggs, there was some dependence on infection levels in the male and female shrimp as indicated by RT-PCR. RT-nested PCR data on GAV levels in eggs, nauplii, protozoea and PL5 progeny of the artificial matings suggests that vertically transmitted virus is most probably associated with the egg surface.


title: Job characteristics: their relationship to job satisfaction, stress and depression.

text: This study investigated the influences of job characteristics on job satisfaction, stress and depression among South African white collar workers. Participants were managers in full-time employment with large organisations. They completed the Job Diagnostic Survey, the Perceived Stress Scale and the Beck Depression Inventory. A regression approach was used to predict job satisfaction, stress and depression from job characteristics. Job characteristics (skill variety, task identity, task significance, autonomy and feedback) predicted job satisfaction, as well as stress and depression. Job characteristics are weak predictors of perceived stress and depression. Work related factors, such as interpersonal relations and organisational culture, may better predict mental health in work settings.


title: [Clinical observation on treatment of 40 SARS uncertain patients with integrative traditional Chinese and Western medicine].

text: OBJECTIVE To observe the clinic symptom improving time in uncertain SARS patients and the therapeutic effect of integrative Chinese and western medicine (ICWM) in treating SARS. METHODS The clinic symptoms, chest film and tongue figure of 40 uncertain SARS patients treated with ICWM were observed and T-lymphocyte subsets, serum coronavirus nucleic acid and antibody in 20 patients were tested dynamically. RESULTS All the symptoms, such as fever, sweating, fatigue, cough without phlegm, etc. were obviously improved after treatment. Lung shadow in chest film began to be absorbed 4.54 +/- 2.85 days, and obviously absorbed 7.74 +/- 4.68 days after treatment. CD3, CD4 and CD8 in 20 patients, which were lower than the normal range when hospitalization, began to increase 3 days later and gradually recovered to the normal in 6-10 days. Serum coronavirus nucleic acid was positive in 3 patients, coronavirus antibody positive in two and both were positive in one. CONCLUSION ICWM can improve the symptoms and regulate the immune function in uncertain SARS patients.


title: Severe acute respiratory syndrome (SARS) in neonates and children.

text: Severe acute respiratory syndrome (SARS) runs a more benign course in children during the acute phase. Infants born to mothers with the disease did not acquire the infection through vertical transmission. The treatment strategy for children with SARS has not been standardised and is based on adult experience. Thus far, no deaths have been reported in the paediatric age group. Exercise impairment and residual radiological abnormalities were present six months after diagnosis. It is important to assess these patients on a regular basis to detect and provide appropriate management for any persistent or emerging long term sequelae in the physical, psychological, and social domains. This review describes the current understanding of SARS coronavirus infection in newborns and children.


title: Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway.

text: Besides genes that are homologous to proteins found in other coronaviruses, the severe acute respiratory syndrome coronavirus genome also contains nine other potential open reading frames. Previously, we have characterized the expression and cellular localization of two of these "accessory" viral proteins, 3a (previously termed U274) and 7a (previously termed U122). In this study, we further examined whether they can induce apoptosis, which has been observed clinically. We showed that the overexpression of 7a, but not of 3a or the viral structural proteins, nucleocapsid, membrane, and envelope, induces apoptosis. 7a induces apoptosis via a caspase-dependent pathway and in cell lines derived from different organs, including lung, kidney, and liver.


title: Outcomes of Laparoscopic Treatment in Women with Cesarean Scar Syndrome.

text: BACKGROUND The aim of this study was to evaluate the outcomes of laparoscopic treatment of women with severe defect of a Cesarean section (CS) scar and Cesarean scar syndrome. MATERIAL AND METHODS A prospective longitudinal study was conducted in 11 women who were treated for Cesarean scar syndrome. Ultrasound examinations were performed transvaginally 1 day before surgery and 6 months after laparoscopy in all women. Clinical data were registered 1 day before laparoscopy and 6 months after laparoscopy. RESULTS Of these 11 women, total dehiscence of the CS scar was present in 72.7% (8/11) of the women. Before laparoscopy, all 11 women had severe defect of the CS scar (DRC ≤0.25); however, 6 months after laparoscopy, 81.8% (9/11) of women still had severe defect of the CS scar. Mean thickness of the CS scar, measured 1 day before and 6 months after laparoscopy in all 11 women, was 0.3±0.4 mm and 1.3±1.0 mm, respectively. Accordingly, no significant differences were observed in the mean CS scar thickness (p=0.101). After laparoscopy, 63.6% (7/11) of women were fully asymptomatic, and among the remaining 4, the most common complications were dyspareunia in 36.4% (4/11, p=0.005), pelvic pain in 27.3% (3/11, p=0.014), and dysmenorrhea in 18.2% (2/11, p=0.01), and best results after laparoscopy were achieved for postmenstrual spotting in 18.2% (2/11, p<0.001). CONCLUSIONS Improvement of women's health after laparoscopy does not necessarily mean improvement of CS scar sonomorphology. Surgery should be offered only to women with symptoms of the Cesarean scar syndrome.


Methicillin-resistant Staphylococcus aureus.


title: Risk factors associated with the prevalence of footrot in sheep from 1999 to 2000.

text: A postal survey of the techniques being used for the treatment and control of footrot in sheep flocks between November 1999 and October 2000 was conducted in England and Wales in November 2000. Of the 392 questionnaires circulated, 251 (64 per cent) were returned, and 209 of these were usable. Negative binomial regression analysis indicated that the isolation of bought-in sheep, and the separation and individual treatment of diseased sheep with parenteral antibiotics, foot trimming and topical foot sprays were associated with a significantly lower prevalence of footrot in a flock. In contrast, ewe flocks which were routinely foot trimmed more than once a year had a significantly higher prevalence of footrot. No evidence was found that footbathing a flock reduced the level of footrot, except on the 14 per cent of farms where the penning and race facilities for footbathing were reported by the farmer to be excellent. Vaccination had no significant beneficial effect on the level of footrot in a flock


title: Vesicular stomatitis virus pseudotyped with severe acute respiratory syndrome coronavirus spike protein.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) contains a single spike (S) protein, which binds to its receptor, angiotensin-converting enzyme 2 (ACE2), induces membrane fusion and serves as a neutralizing antigen. A SARS-CoV-S protein-bearing vesicular stomatitis virus (VSV) pseudotype using the VSVDeltaG* system was generated. Partial deletion of the SARS-CoV-S protein cytoplasmic domain allowed efficient incorporation into VSV particles and led to the generation of a pseudotype (VSV-SARS-St19) at high titre. Green fluorescent protein expression was demonstrated as early as 7 h after infection of Vero E6 cells with VSV-SARS-St19. VSV-SARS-St19 was neutralized by anti-SARS-CoV antibody and soluble ACE2, and its infection was blocked by treatment of Vero E6 cells with anti-ACE2 antibody. These results indicated that VSV-SARS-St19 infection is mediated by SARS-CoV-S protein in an ACE2-dependent manner. VSV-SARS-St19 will be useful for analysing the function of SARS-CoV-S protein and for developing rapid methods of detecting neutralizing antibodies specific for SARS-CoV infection.


title: Otitis media in preweaned Holstein dairy calves in Michigan due to Mycoplasma bovis.

text: Mycoplasma bovis was isolated from the tympanic bullae of dairy calves with an exudative otitis media. The history, clinical signs, gross and histologic lesions, and bacteriologic findings are described for 5 preweaned Holstein calves with otitis media from a 600-cow dairy in Michigan. Clinical findings consisted of unilateral or bilateral ear droop, epiphora, head tilt, and recumbency in severely affected calves. Postmortem examination revealed unilateral or bilateral fibrinosuppurative to caseous exudate in the tympanic bullae. Histologically, a marked fibrinosuppurative to caseous exudate filled the tympanic air spaces. The partially ulcerated tympanic mucosa was markedly thickened with mononuclear cell infiltration and proliferation of fibrous connective tissue. Bone remodeling and periosteal hyperostosis were present in some osseous septa. Mycoplasma bovis was isolated from the tympanic bullae of all 5 calves and from the lungs of 2 calves and the frontal sinus of 1 calf. Mycoplasma bovis was isolated at > 100,000 colony forming units/ml from the bulk milk tank of the farm of origin. The isolation of M. bovis from the bulk milk tank, indicating subclinical mycoplasmal mastitis coupled with the feeding of waste milk from mastitic cows to calves is suggestive of a possible source of the infection resulting in otitis media in preweaned dairy calves.


Preparedness for Ebola Virus Disease.


title: Development of human monoclonal antibodies against diseases caused by emerging and biodefense-related viruses.

text: Polyclonal antibodies have a century-old history of being effective against some viruses; recently, monoclonal antibodies (mAbs) have also shown success. The humanized mAb Synagis (palivizumab), which is still the only mAb against a viral disease approved by the US FDA, has been widely used as a prophylactic measure against respiratory syncytial virus infections in neonates and immunocompromised individuals. The first fully human mAbs against two other paramyxoviruses, Hendra and Nipah virus, which can cause high (up to 75%) mortality, were recently developed; one of them, m101, showed exceptional potency against infectious virus. In an amazing pace of research, several potent human mAbs targeting the severe acute respiratory syndrome coronavirus S glycoprotein that can affect infections in animal models have been developed months after the virus was identified in 2003. A potent humanized mAb with therapeutic potential was recently developed against the West Nile virus. The progress in developing neutralizing human mAbs against Ebola, Crimean-Congo hemorrhagic fever, vaccinia and other emerging and biodefense-related viruses is slow. A major problem in the development of effective therapeutic agents against viruses, including therapeutic antibodies, is the viruses' heterogeneity and mutability. A related problem is the low binding affinity of crossreactive antibodies able to neutralize a variety of primary isolates. Combinations of mAbs or mAbs with other drugs, and/or the identification of potent new mAbs and their derivatives that target highly conserved viral structures, which are critical for virus entry into cells, are some of the possible solutions to these problems, and will continue to be a major focus of antiviral research.


title: Two-port laparoscopic anterior resection through a self-made glove device versus conventional laparoscopic anterior resection for rectal cancer: a comparison of short-term surgical results.

text: BACKGROUND The laparoscopic approach has become increasingly incorporated into the development of new surgical procedures. An ever-increasing number of surgeons desire methods that minimize surgical trauma and provide improved cosmetic outcomes. Since 2014, we have performed two-port laparoscopic surgery using a transumbilical multichannel glove port and a 12-mm port. The aim of this study was to compare the short-term surgical results of two-port laparoscopic anterior resection (TPLAR) with those of conventional laparoscopic anterior resection (CLAR) for rectal cancer. METHODS Between January 2014 and May 2014, a total of 27 patients underwent TPLAR and 30 patients underwent CLAR for the treatment of rectal cancer. The short-term surgical results of these two groups of patients were analyzed retrospectively. RESULTS The differences in operative time, blood loss, conversion rate, complication rate, distal resection margin, number of harvested lymph nodes, duration until ambulation, duration until first flatus, length of postoperative hospital stay, and overall hospital costs between the two groups were not significant. The median (range) length of the abdominal incisions of the TPLAR patients was shorter than the length of the CLAR patients (5.1 (4.5-16.3) cm vs 8.2 (7.0-10.0) cm, respectively; p < 0.001). The respective median (range) postoperative pain scores were lower in the TPLAR than in the CLAR patients at 24 h (4 (1-6) h vs 5 (2-8) h; p = 0.045), 48 h (3 (1-4) h vs 4 (range 1-8) h; P = 0.004) and 72 h (1 (0-3) h vs 2 (1-5) h; p = 0.010). The median overall score on the satisfaction-with-abdominal-incision questionnaire of the TPLAR patients was significantly higher (better) than the score of the CLAR patients. CONCLUSIONS TPLAR for rectal cancer is safe and feasible, with short-term perioperative and oncological outcomes similar to those of CLAR. TPLAR provides less postoperative pain and better cosmetic outcomes.


title: Safety of patients isolated for infection control.

text: CONTEXT Hospital infection control policies that use patient isolation prevent nosocomial transmission of infectious diseases, but may inadvertently lead to patient neglect and errors. OBJECTIVE To examine the quality of medical care received by patients isolated for infection control. DESIGN, SETTING, AND PATIENTS We identified consecutive adults who were isolated for methicillin-resistant Staphylococcus aureus colonization or infection at 2 large North American teaching hospitals: a general cohort (patients admitted with all diagnoses between January 1, 1999, and January 1, 2000; n = 78); and a disease-specific cohort (patients admitted with a diagnosis of congestive heart failure between January 1, 1999, and July 1, 2002; n = 72). Two matched controls were selected for each isolated patient (n = 156 general cohort controls and n = 144 disease-specific cohort controls). MAIN OUTCOME MEASURES Quality-of-care measures encompassing processes, outcomes, and satisfaction. Adjustments for study cohort and patient demographic, hospital, and clinical characteristics were conducted using multivariable regression. RESULTS Isolated and control patients generally had similar baseline characteristics; however, isolated patients were twice as likely as control patients to experience adverse events during their hospitalization (31 vs 15 adverse events per 1000 days; P<.001). This difference in adverse events reflected preventable events (20 vs 3 adverse events per 1000 days; P<.001) as opposed to nonpreventable events (11 vs 12 adverse events per 1000 days; P =.98). Isolated patients were also more likely to formally complain to the hospital about their care than control patients (8% vs 1%; P<.001), to have their vital signs not recorded as ordered (51% vs 31%; P<.001), and more likely to have days with no physician progress note (26% vs 13%; P<.001). No differences in hospital mortality were observed for the 2 groups (17% vs 10%; P =.16). CONCLUSION Compared with controls, patients isolated for infection control precautions experience more preventable adverse events, express greater dissatisfaction with their treatment, and have less documented care.


title: Specific cytotoxic T lymphocytes are involved in in vivo clearance of infectious bronchitis virus.

text: Cytotoxic T-lymphocyte (CTL) responses to infectious bronchitis virus (IBV) were determined at regular intervals between 3 and 30 days postinfection (p.i.). The maximum response with 82% lysis of labeled target cells was detected at 10 days p.i. The specific CTL response did not begin to decline until the amount of virus, which peaked at day 8 p.i. in both the kidneys and lungs, started to decrease. Clinical respiratory signs of illness also correlated with amount of virus. CTL activity was shown to be major histocompatibility complex (MHC) class restricted because the lysis of MHC-mismatched targets was negligible, and lysis was mediated by CD8+ CD4- T cells, as the CTL response could be abolished with removal of CD8+ CD4- but not CD4+ CD8- lymphocytes. In contrast, immunoglobulin M (IgM) antibody was not detected until day 10 p.i., and levels peaked at day 12 p.i.; IgG antibody levels were minimal until day 15 p.i. but continued to increase exponentially until day 30 p.i., the last day examined. In summary, CTL responses correlated with initial decreases in infection and illness.


title: Esophageal stripping creates a clear operative field for lymph node dissection along the left recurrent laryngeal nerve in prone video-assisted thoracoscopic surgery.

text: We describe a 54-year-old man in whom esophageal carcinoma was diagnosed and who underwent video-assisted thoracoscopic surgery of the esophagus (VATS-E) in the prone position. Initially, the patient was fixed in a semiprone position, from which he could be rotated to a prone or left lateral position. Four ports were inserted, and then the patient was rotated to the prone position. Once the patient was prone, gravity caused the lung to move downwards. Next, the chest cavity was inflated with a CO(2) insufflation pressure of 6 mm Hg. Esophagectomy was then performed, and the lymph nodes in the middle and lower mediastinum and along the right recurrent laryngeal nerve were dissected. In the left upper mediastinum, lymph node dissection was performed after the residual esophagus was stripped. Stripping of the residual esophagus created sufficient working space and a clear operative field for lymph node dissection. VATS-E in the prone position has achieved remarkable results in Japan. It allows a clear operative view of the middle and lower mediastinum, but the working space in the upper mediastinum is limited. Our results indicate that esophageal stripping in prone VATS-E allows for safe and straightforward lymph node dissection along the left recurrent laryngeal nerve. Our technique overcame the difficulties usually encountered with this type of lymph node dissection.


title: Identification of viral agents associated with diarrhea in young children during a winter season in Beijing, China.

text: BACKGROUND Viral diarrhea remains a major cause of childhood morbidity and mortality worldwide. Although rotavirus was extensively studied in China, few comprehensive studies of all viral agents related to diarrhea in children have been conducted. OBJECTIVES Our study was performed to investigate the role of enteric viruses in acute diarrhea in our country and to evaluate methods that could be used in routine diagnostics. STUDY DESIGN One hundred stool samples were collected from children under 5 years of age seeking medical care for acute diarrhea during the winter season 2000/2001 in Beijing Children's Hospital. All specimens were initially screened microscopically for leucocytes/red blood cells. Samples with negative results were analyzed for virus presence using commercial EIAs and/or in-house RT-PCRs. RESULTS At least one viral agent was found in 67% of the specimens. The frequency of rotavirus, astrovirus, norovirus and enteric adenovirus was 59%, 8%, 6% and 2%, respectively. Dual infections were found in 9.0% (6/67) of the positive samples. The results from rotavirus and astrovirus EIAs were concordant with those of rotavirus and astrovirus RT-PCRs. CONCLUSIONS Enteric viruses play an important role in pediatric diarrhea during the winter season in China. A combination of microscopic examination of stool samples with specific EIA assays to detect virus antigen in stool specimens may be suitable for routine diagnostics.


title: Identification and antigenic epitope mapping of immunodominant region amino residues 510 to 672 on the spike protein of the severe acute respiratory syndrome coronavirus.

text: The severe acute respiratory syndrome (SARS) is a newly emerging human infectious disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV). The spike (S) protein of SARS-CoV is a major virion structural protein. It plays an important role in the interaction with receptors and neutralizing antibodies. In this study, the S1 domain of the spike protein and three truncated fragments were expressed by fusion with GST in a pGEX-6p-1 vector. Western blot results demonstrated that the 510-672 fragment of the S1 domain is a linear epitope dominant region. To map the antigenic epitope of this linear epitope dominant region, a set of 16 partially overlapping fragments spanning the fragment were fused with GST and expressed. Four antigenic epitopes S1C3 (539-559), S1C4 (548-567), S1C7/8 (583-606), and S1C10/11 (607-630) were identified. Immunization of mice with each of the four antigenic epitope-fused proteins revealed that all four proteins could elicit spike protein specific antisera. All of them were able to bind to the surface domain of the whole spike protein expressed by recombinant baculovirus in insect cells. Identification of antigenic epitopes of the spike protein of SARS-CoV may provide the basis for the development of immunity-based prophylactic, therapeutic, and diagnostic clinical techniques for the severe acute respiratory syndrome.


title: Alpha-1 adrenergic receptor antagonists for preventing acute respiratory distress syndrome and death from cytokine storm syndrome.

text: In severe viral pneumonias, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by a hyperinflammatory reaction ('cytokine storm syndrome') that leads to acute respiratory distress syndrome and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes. We previously demonstrated that alpha-1 adrenergic receptor antagonists ($\alpha$-blockers) can prevent cytokine storm syndrome and death in mice. Here, we conduct a retrospective analysis of patients with acute respiratory distress or pneumonia (n = 13,125 and n = 108,956, respectively) from all causes; patients who were incidentally taking $\alpha$-blockers had a reduced risk of requiring ventilation (by 35% and 16%, respectively), and a reduced risk of being ventilated and dying (by 56% and 20%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects. These results highlight the urgent need for prospective trials testing whether prophylactic $\alpha$-blockers improve outcomes in diseases with a prominent hyperinflammatory component such as COVID-19.


The continuing risk of transfusion-transmitted infections.


title: Human cytomegalovirus elicits a coordinated cellular antiviral response via envelope glycoprotein B.

text: Previous studies have shown that human cytomegalovirus (CMV) is a potent elicitor of interferon-stimulated gene (ISG) expression. Induction of the interferon pathway does not require replication-competent virus, and envelope glycoprotein B (gB) from CMV is a viral structural component that can directly induce transcription of ISGs. Here we extend these earlier findings by defining the consequences of inducing the interferon pathway. We found that cells respond to CMV or soluble gB by establishing a functional antiviral state within cell types critical in CMV biology, such as fibroblasts and endothelial cells. We have also discovered new insights into the mechanism by which the pathway is initiated. Interferon regulatory factor 3 (IRF3), a key transcriptional regulator of cellular interferon responses, is activated by CMV virions and soluble gB. Thus, IRF3 becomes activated via "outside-in" signal transduction events. This is a novel mechanism of activation of this key transcription factor by viruses. In comparison to soluble gB (gB(1-750)), which comprises the entire ectodomain of gB, a truncation mutant encompassing only the amino-terminal region of gB (gB(1-460)) was markedly less effective at inducing antiviral responses. This indicates that the region of gB from residues 461 to 750 is important for initiation of the antiviral response. In addition, CMV and gB establish an antiviral state in alpha/beta interferon null cells, illustrating that primary induction of ISGs by CMV and gB is sufficient to establish the antiviral response and that interferon secretion is not necessary for the antiviral effect. Taken together, our findings reveal that CMV initiates a coordinated antiviral response through contact between gB and an as-yet-unidentified cell surface receptor(s).


docid: xqsomgyr

title: The challenge of severe acute respiratory syndrome (SARS) in dentistry.

text: Severe Acute Respiratory Syndrome (SARS) is caused by a newly identified coronavirus, called SARS-associated coronavirus (SARS-CoV) that appears to be transmitted primarily through droplets of saliva. This is the reason why the most important international organizations recommend that the dentists adopt a unique preventive approach to the problem: SARS patients should not be treated in the dental office. This is possible only if a suspected case of SARS is correctly and promptly identified. But a correct identification is made difficult by several factors, such as the incubation period, a possibly asymptomatic onset of the illness, the still low specificity and sensitivity of laboratory and instrumental tests. A case or suspected case of SARS may thus unwillingly be treated at the dental office. It is therefore necessary to adopt protective measures for the dental personnel and to implement and enforce infection control measures in order to eliminate the risk of viral contamination. Nonetheless, these procedures do not ensure a complete elimination of SARS-CoV contamination risk since a major risk is represented by blood-borne infection, which is originated by the mouth of patients, and the contamination of dental units water lines (DUWLs) is most difficult to control. Blood-borne contamination may be achieved only by adopting a high level, between-patients disinfection protocol of the DUWLs based on the use of chemical agents with biocidal activity against spores, viruses, bacteria and fungi (Autosteril method). In conclusion a fully effective control of the cross-infection risk will be obtained only by adopting a correct, integrated use of different infection control procedures.


docid: lepomuqk

title: Clinical exome sequencing in neurologic disease.

text: PURPOSE OF REVIEW The landscape of genetic diagnostic testing has changed dramatically with the introduction of next-generation clinical exome sequencing (CES), which provides an unbiased analysis of all protein-coding sequences in the roughly 21,000 genes in the human genome. Use of this testing, however, is currently limited in clinical neurologic practice by the lack of a framework for appropriate use and payer coverage. RECENT FINDINGS CES can be cost-effective due to its high diagnostic yield in comparison to other genetic tests in current use and should be utilized as a routine diagnostic test in patients with heterogeneous neurologic phenotypes facing a broad genetic differential diagnosis. CES can eliminate the need for escalating sequences of conventional neurodiagnostic tests. SUMMARY This review discusses the role of clinical exome sequencing in neurologic disease, including its benefits to patients, limitations, appropriate use, and billing. We also provide a reference template policy for payer use when considering testing requests.


docid: otvljwhu

title: Morphology and morphogenesis of severe acute respiratory syndrome (SARS)-associated virus.

text: After infecting the Vero E6 cells by nasal/throat swabs collected from SARS patients, we studied the SARS-associated virus by electron microscopy and molecular biological technique. The results show that the diameter of newly isolated virus is about 50 nm without envelope or 100 nm with envelope. The virus was proved to be a new coronavirus by RT-PCR and it responded positively to convalescent-phase serum specimen from SARS patients, which is the evidence that this new virus is etiologically linked to the outbreak of SARS. The morphogenesis and distribution of the virus are also discussed in this article.


docid: hlsghssm

title: 21st-century emerging and reemerging infections.


title: Laparoscopic-assisted ovariectomy of tigers (Panthera tigris) with the use of the LigaSure device.

text: Laparoscopic ovariectomy was performed in seven tigers with the use of a vessel-sealing device and a three-port technique. A comparison group of seven tigers that underwent traditional ovariohysterectomy was assembled with the use of a medical records search. Mean operative times for laparoscopic ovariectomy were compared to standard ovariohysterectomy, and mean combined laparoscopic incision length compared to standard ovariohysterectomy incision lengths. Significance was set at P < or = 0.05. Mean surgical time for laparoscopic ovariectomy (82 min, range 71-126 min) was significantly shorter than standard ovariohysterectomy surgical time (129 min, range 80-165 min, P = 0.007). Mean combined laparoscopic incision length (8.07 cm, range 3.80-9.50 cm) was significantly shorter than the mean incision length for standard ovariohysterectomy (13.57 cm, range 12.00-20.00 cm, P = 0.009). There were no clinically important complications observed in either group. Laparoscopic ovariectomy has a significantly shorter surgical time and combined incision length compared to standard ovariohysterectomy in tigers, and appears to be a safe and rapid sterilization method for tigers. Equipment cost and the necessity for advanced training may limit its use in some institutions. Further prospective evaluation is warranted to determine whether it is associated with decreased morbidity, mortality, or cost.


Non-contact infrared thermal imagers for mass fever screening--state of the art or myth?


title: Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - A better synergy for future COVID-19 clinical trials.

text: The recent outbreak of coronavirus disease 2019 (COVID-19), is now officially declared as a pandemic by the World Health Organization. As of now, there is no known effective pharmaceutical agent against the SARS-CoV-2 virus. However, several precautionary measures have been prescribed to prevent further spread of the virus, which include avoidance of social gatherings, proper handwashing, frequently disinfecting of used items and surfaces and so on. More recent studies have highlighted the possibility of treating patients infected with the novel SARS-CoV-2 virus with chloroquine and hydroxychloroquine, of which mechanism of action is not completely understood. We seek to draw the attention of the scientific community to the possibility of drastically reducing the effects of the virus on the affected patients and improving clinical trials outcome through the synergistic action of zinc and chloroquine in patients suffering from the coronavirus disease.


docid: nfnwdwez

title: 743: ACUTE INFLAMMATORY RESPONSE TO TRAUMATIC BRAIN INJURY IS AFFECTED BY MODULATORS OF GUT MICROBIOTA.


docid: jmkncvfz

title: Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma.

text: BACKGROUND Respiratory infections are well known triggers of asthma exacerbations, but their role in stable adult asthma remains unclear. METHODS 103 asthmatics and 30 control subjects were enrolled in the study. Sputum was induced by inhalation of 3% NaCl solution. Oropharyngeal swab specimens were obtained from the posterior wall of the oropharynx. Respiratory specimens were analysed by RT-PCR for rhinovirus, enterovirus and respiratory syncytial virus and by PCR for adenovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis. RESULTS Sputum samples from two of the 30 healthy controls (6.7%), five of 53 patients with mild asthma (9.4%), and eight of 50 with moderate asthma (16.0%) were positive for rhinovirus. Rhinovirus positive asthmatic subjects had more asthma symptoms and lower forced expiratory volume in 1 second (FEV(1)) (79% predicted) than rhinovirus negative cases (93.5% predicted; p = 0.020). Chlamydia pneumoniae PCR was positive in 11 healthy controls (36.6%), 11 mild asthmatics (20.8%), and 11 moderate asthmatics (22%), and PCR positive asthmatics had lower FEV(1)/FVC than negative cases (78.2% v 80.8%, p = 0.023). Bordetella pertussis PCR was positive in 30 cases: five healthy controls (16.7%), 15 mild asthmatics (28.3%), and 10 moderate asthmatics (20%). Bordetella pertussis positive individuals had lower FEV(1)/FVC (77.1% v 80.7%, p = 0.012) and more asthma symptoms than B pertussis negative cases. CONCLUSIONS Rhinovirus, C pneumoniae, and B pertussis are found in the sputum or pharyngeal swab specimens of asthmatic subjects without concurrent symptoms of infection or asthma exacerbation, as well as in some healthy controls. Positivity is associated with lower lung function and more frequent asthma symptoms.


Laboratory experiments on oral vaccination of calves against rotavirus or coronavirus induced diarrhoea.


title: Effects of oral lactose and xylose loads on blood glucose, galactose, xylose, and insulin values in healthy calves and calves with diarrhea.

text: OBJECTIVE 2 hypotheses were tested: calves with acute, mild diarrhea digest lactose less efficiently than healthy calves, and they are in a catabolic state, which influences plasma glucose concentration after glucose absorption. DESIGN Clinical study; 2 treatments with 10 repetitions/treatment. ANIMALS 20 preruminant Brown Swiss and Simmental Red Holstein calves; 10 calves with mild diarrhea, and 10 age-matched healthy calves. PROCEDURE Blood metabolite and hormone concentrations were determined before and after an oral lactose load. Plasma xylose concentration was determined after an oral xylose load. III calves were tested 1 day after the onset of diarrhea. RESULTS Calves with diarrhea (cryptosporidia, coronavirus) had lower preprandial concentrations of plasma glucose, insulin-like growth factor 1, and 3,5,3-triiodothyronine (P < 0.01) and a higher concentration of free fatty acids (P < 0.03) than did healthy calves. After the oral lactose and xylose loads, blood galactose and plasma xylose concentrations were lower in ill calves (P = 0.10 and P = 0.07, respectively). In calves with diarrhea, there was a larger increase of plasma glucose concentration (P = 0.12) and a smaller increase of plasma insulin concentration (P = 0.04) above baseline values after lactose ingestion. CONCLUSIONS Lactose digestion is slightly impaired in calves with mild diarrhea. Calves with acute diarrhea are in a catabolic state and, therefore, respond with a larger increase of plasma glucose concentration to a given amount of absorbed glucose than do healthy calves. CLINICAL-RELEVANCE: Plasma glucose concentration is not a reliable measure for glucose absorption in animals that are in a catabolic state.


docid: kbkrkyhr

title: Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein.

text: To localize the epitopes recognized by monoclonal antibodies (MAbs) specific for the S1 subunit of the murine coronavirus JHMV spike protein, we have expressed S1 proteins with different deletions from the C terminus of S1. S1utt is composed of the entire 769-amino-acid (aa) S1 protein; S1NM, S1N, S1n(330), and S1n(220) are deletion mutants with 594, 453, 330, and 220 aa from the N terminus of the S1 protein. The expressed S1 deletion mutant proteins were examined for reactivities to a panel of MAbs. All MAbs classified in groups A and B, those reactive to most mouse hepatitis virus (MHV) strains and those specific for isolate JHMV, respectively, recognized S1N(330) and the larger S1 deletion mutants but failed to react with S1N(220). MAbs in group C, specific for the larger S protein of JHMV, reacted only with the S1utt protein without any deletion. These results indicated that the domain composed of the N-terminal 330 aa comprised the cluster of conformational epitopes recognized by MAbs in groups A and B. It was also shown that the epitopes of MAbs in group C were not restricted to the region missing in the smaller S protein. These results together with the fact that all MAbs in group B retained high neutralizing activity suggested the possibility that the N-terminal 330 aa are responsible for binding to the MHV-specific receptors. In investigate this possibility, we expressed the receptor protein and examined the binding of each S1 deletion mutant to the receptor. It was demonstrated that the S1N(330) protein as well as other S1 deletion mutants larger than S1N(330) bound to the receptor. These results indicated that a domain composed of 330 aa at the N terminus of the S1 protein is responsible for binding to the MHV-specific receptor.


COVID-19 Guidelines for Sports and Physical Activity.


title: An assessment of electronically captured data in the patient care enhancement system (PACES) for syndromic surveillance.

text: INTRODUCTION A common approach to the surveillance of emerging infectious diseases and agents of bioterrorism is to analyse electronically captured data for disease syndromes. The Patient Care Enhancement System (PACES) is a form of electronic medical records presently in service in the Singapore Armed Forces (SAF). We assess the feasibility of PACES data for surveillance, describe time-trends, and identify methods of sub-analysis which could improve performance. MATERIALS AND METHODS Medical consults from July 2000 to June 2003 were extracted. Diagnosis codes were mapped to 7 infectious disease syndromes according to the categorisation in the Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE): gastrointestinal (GI), fever (FEVER), respiratory, (RESP), coma (COMA), neurological (NEURO), dermatologic-haemorrhagic (DERMHEM) and dermatologic- infectious (DERM-INF). RESULTS A total of 732,233 episodes of care were analysed. Weekly periodicity was observed, with decreased weekend consults; there were no obvious seasonal trends in any of the syndromes. RESP, FEVER and GI syndromes were common events. Sub-analyses, either by restricting to cases with a repeated consultation, or grouping the data by medical centres, could dramatically lower thresholds used to flag outbreaks. CONCLUSION In spite of the level of background noise inherent in a system consisting mainly of primary care consults, sub-analysis by medical centre, or restriction to cases with repeated consults were able to yield sensitive thresholds for outbreak detection.


title: Effect of colostrum intake on diarrhoea incidence in new-born calves.

text: In a survey which lasted one year and included data of 73 dairy cows with their calves, colostrum immunoglobulin G (IgG) of 22 primiparous cows and serum IgG of their calves were lower than the corresponding IgG levels of 51 multiparous cows and their calves. Serum IgG concentration was not correlated with diarrhoea incidence. Although there were no seasonal differences in the IgG concentration of colostrum and calf serum, neonatal diarrhoea incidence was higher in calves which were born in winter than in calves which were born in summer (P < 0.01). Thus the high diarrhoea incidence in winter was not a consequence of an insufficient IgG transfer to the calves. The 60 calves of the second study were fed colostrum on the first day of life. From the second to the tenth day 28 experimental calves received milk and 0.5 l of surplus colostrum of the first and second milking twice a day, whereas 32 control calves received milk only twice a day. Two of the 28 experimental and 11 of the 32 control calves suffered from diarrhoea during the first ten days of life (P < 0.05). These results show that the ingestion of surplus colostrum in addition to milk after the first day of life protects the new-born calf against infectious diarrhoea.


title: New agents modulating the renin-angiotensin-aldosterone system-Will there be a new therapeutic option?

text: The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT1 receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT1 axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders.


The internet, a simple and convenient tool in Chlamydia trachomatis screening of young people.


title: Incidence, etiology, and symptomatology of upper respiratory illness in elite athletes.

text: PURPOSE Upper respiratory illness (URI) is the most common medical condition affecting elite athletes. The aims of this study were to identify and evaluate the incidence, pathogenic etiology, and symptomatology of acute URI during a 5-month training and competition period. METHODS Thirty-two elite and 31 recreationally competitive triathletes and cyclists, and 20 sedentary controls (age range 18.0-34.1 yr) participated in a prospective surveillance study. Nasopharyngeal and throat swabs were collected from subjects presenting with two or more defined upper respiratory symptoms. Swabs were analyzed using microscopy, culture, and PCR testing for typical and atypical respiratory pathogens. The Wisconsin Upper Respiratory Symptom Survey (WURSS-44) was used to assess symptomatology and functional impairment. RESULTS Thirty-seven URI episodes were reported in 28 subjects. Incidence rate ratios for illness were higher in both the control subjects (1.93, 95% CI: 0.72-5.18) and elite athletes (4.50, 1.91-10.59) than in the recreationally competitive athletes. Infectious agents were identified in only 11 (two control, three recreationally competitive, and six elite) out of 37 illness episodes. Rhinovirus was the most common respiratory pathogen isolated. Symptom and functional impairment severity scores were higher in subjects with an infectious pathogen episode, particularly on illness days 3-4. CONCLUSION The results confirm a higher rate of URI among elite athletes than recreationally competitive athletes during this training and competition season. However, because pathogens were isolated in fewer than 30% of URI cases, further study is required to uncover the causes of unidentified but symptomatic URI in athletes. Despite the common perception that all URI are infections, physicians should consider both infectious and noninfectious causes when athletes present with symptoms.


title: Risk Factors for Cholangiocarcinoma in Thailand: A Systematic Review and Meta-Analysis

text: Background and objective: Cholangiocarcinoma remains a serious public health concern in Thailand. While many of the risk factors for cholangiocarcinoma in western countries are well-recognized, it remains unclear whether they are the same in Thailand. We set out to investigate the risk factors for cholangiocarcinoma in Thailand. Methods: Starting March 4, 2016, we reviewed studies found using pre-specified keywords on SCOPUS, Pro Quest Science Direct, PubMed, and online public access catalog of Khon Kaen University. Two review authors independently screened studies for inclusion criteria, extracted data, and assessed the studied Risk of Bias. The Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Tools were used to assess the quality of included studies. The risk effects of factors were estimated as a pooled adjusted odds ratio with a 95% confidence interval. The heterogeneity of results was considered using the I-square, Tau-square and Chi-square statistics. Results: A strong association was found between cholangiocarcinoma and age, Opisthorchis viverrini infection, eating raw cyprinoid fish, family history of cancer, liquor consumption, and taking praziquantel. There was only a mild association found between eating nitrite-containing foods, fresh vegetables, education, smoking behavior, and sex. No association was found between cholangiocarcinoma and eating fermented fish (Pla-ra), northeastern Thai or Chinese sausage, sticky rice, meat, chewing betel nut, or eating fruit. There were two protective factors including fresh vegetables consumption and education attainment. Conclusion: There are unique risk factors of cholangiocarcinoma in Thailand, including age, Opisthorchis viverrini infection, eating raw cyprinoid fish, family history of cancer, liquor consumption, and taking praziquantel.


title: [Scholia about the pandemia urbi et orbi et orbe generate by de COVID-19 disease.]

text: The Goddess of Health had two daughters, Panacea and Higinia, the fruit of the first is diagnosis, prognosis and treatment, and the fruit of the second is health management, prevention, and statistics. Humanbeings are unexpectedly subjected to:1. Happenings: they belong to the plane of the personality, crisis, the Age of the virus appears that had already been announced. The ideological support is not sustained, causing a bankruptcy in the system of our life. The subject acts unconsciously, does not believe in the advent of the catastrophe, does not follow logical rules, is unable to transcend, fear-anguish appears and this requires a lot of protection. Those who remain free from personal decomposition skewer him and put a project called "person" with his sense of life, his lifestyle and life project, which is the conjunction of body and spirit, which with the agony struggles against life itself.2. Events: they belong to the plane of nature, catastrophes. The use of the word catastrophe is not synonymou swith unavoidable natural disaster, accident, although it is used by the health authorities this can have a great impact on those affected by the virus. This word has the final nuance of Greek tragedies. False arrogance appears, true madness. In the case of the Covid-19 there is something else, a dialectical position with oneself. They lived and we lived on a volcano. The example of the Apocalypse and its three plagues, epidemics and post-war neuroses, etc. The most striking neuropsychiatricsymptomatology is the appearance of "ageusia" and "anosmia", abruptly and totally, which disappears slowly, as well as sleep disturbances with ignagogic images post-traumatic stress charts appear.


[Kronisk syge og udsatte gruppers situation under COVID-19-pandemien].


title: [COVID-19 from the nephrologist's point of view].

text: During the actual pandemic of COVID-19, it has become clear that the virus causing this devastating disease, SARS-CoV2, targets not only the lungs but also other organs. In this article, we discuss the known or suspected interactions between the virus and the kidneys, as well as their clinical presentations. We also discuss how the pandemic has altered the activities of nephrologists and the logistics of a Swiss dialysis center.


title: Dual infection of gnotobiotic calves with bovine strains of group A and porcine-like group C rotaviruses influences pathogenesis of the group C rotavirus.

text: There is serological evidence that bovine group C rotaviruses exist in the United States, but there are no reports of their isolation. Ninety fecal samples from calves with diarrhea, 81 samples from adult cows with diarrhea (winter dysentery), and 20 fecal samples from healthy adult cows were tested for group C rotaviruses by polyacrylamide gel electrophoresis, immune electron microscopy, and reverse transcription-PCR (RT-PCR). Three samples from adult cow diarrhea cases were positive only by RT-PCR, and a group C rotavirus was isolated from a positive sample in monkey kidney (MA104) cells (WD534tc/C). Genetically and serologically, the WD534tc/C strain was more closely related to the Cowden porcine group C strain than to the Shintoku bovine strain. Because the original cow feces also contained a group A rotavirus (detected after passage in cell culture), we hypothesized that such dual-rotavirus infections might play a role in the pathogenesis and host adaptation of rotaviruses. Thus, we examined the pathogenesis of WD534tc/C alone or combined with virulent (IND/A) or attenuated (NCDV/A) bovine group A rotaviruses in gnotobiotic calves. WD534tc/C alone induced diarrhea without (or with limited) virus shedding in inoculated calves (n = 3). In contrast, all calves coinfected with WD534tc/C and IND/A (n = 2) developed diarrhea and shed both viruses, whereas calves coinfected with WD534tc/C and NCDV/A (n = 3) developed diarrhea but did not shed either virus. Infection with WD534tc/C or NCDV/A alone caused only mild villous atrophy (jejunum and/or ileum), whereas dual infection with both viruses induced lesions throughout the small intestine. Although IND/A alone caused villous atrophy, more-widespread small intestinal lesions occurred in calves coinfected with WD534tc/C and IND/A. In conclusion, coinfection of calves with group A rotaviruses enhanced fecal shedding of a bovine group C rotavirus and the extent of histopathological lesions in the small intestines. Thus, our findings suggest a potential novel hypothesis involving dual infections for the adaptation of heterologous rotaviruses to new host species.


title: Replication and pathogenesis of avian influenza A (H5N1) virus infection in polarised human bronchial and alveolar epithelium.

text: 1. In vitro models of polarised human respiratory epithelial cells were established to investigate the tropism and innate host responses of influenza A (H5N1 and H1N1) viruses. 2. Both viruses efficiently infected alveolar epithelial cells of both the apical and basolateral surfaces of the epithelium, whereas release of newly formed virus was mainly from the apical surface of the epithelium. 3. H5N1 virus was a more potent inducer of cytokines and chemokines in alveolar epithelial cells than H1N1 virus. Such chemokines were secreted onto both the apical and basolateral surfaces of the polarised alveolar epithelium. 4. In bronchial epithelium, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells than did H1N1 virus. In contrast, in well-differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response than did H1N1 virus. 5. Recombinant virus with vRNPs of a mammalian PB2 and an avian PB1 had the strongest polymerase activities, and replicated better in human cell cultures, especially at a high incubation temperature. These viruses were potent inducers of cytokines and chemokines in primary human alveolar epithelial cells.


title: Topology of the membrane-associated hepatitis C virus protein NS4B.

text: Hepatitis C virus (HCV) belongs to the Hepacivirus genus in the Flaviviridae family. Among the least known viral proteins in this family is the nonstructural protein NS4B, which has been suggested to be a part of the replication complex. Hydrophobicity plots indicate a common profile among the NS4B proteins from different members of the Flaviviridae family, suggesting a common function. In order to gain a deeper understanding of the nature of HCV NS4B, we have determined localization and topology of this protein by using recombinant HCV NS4B constructs. The protein localized to the endoplasmic reticulum (ER), but also induced a pattern of cytoplasmic foci positive for markers of the ER. Computer predictions of the membrane topology of NS4B suggested that it has four transmembrane segments. The N and C termini were anticipated to be localized in the cytoplasm, because they are processed by the cytoplasmic NS3 protein. By introducing glycosylation sites at various positions in HCV NS4B, we show that the C terminus is cytoplasmic and the loop around residue 161 is lumenal as predicted. Surprisingly, the N-terminal tail was translocated into the lumen in a considerable fraction of the NS4B molecules, most likely by a posttranslational process. Interestingly, NS4B proteins of the yellow fever and dengue viruses also have their N termini located in the ER lumen due to an N-terminal signal peptide not found in NS4B of HCV. A shared topology achieved in two different ways supports the notion of a common function for NS4B in FLAVIVIRIDAE:


title: [An immunofluorescence assay for the detection of SARS associated coronavirus antibody based on recombinant nucleocapsid antigen and its application].

text: OBJECTIVE To establish a new technique for SARS-CoV antibody test to detect infection of severer acute respiratory syndrome (SARS). METHODS Nucleocapsid gene was obtained by reverse transcription and polymerase chain reaction from a SARS patient and inserted into the vector pFastBacHTa expressing baculovirus. Insect Sf9 cells were transfected with the recombinant baculovirus expressing SARS nucleocapsid antigen and then cultured, fixed by acetone so as to make SARS-specific antigen. Immunofluorescence assay (IFA) technique and plaque reduction neutralization test (PRNT) were used to detect 7 samples of sera of 4 newly diagnosed SARS patients collected in different days, 48 samples of convalescent sera of SARS patients, 24 serum samples of healthy person undergoing physical examination, and 40 serum samples from non-SARS patients with fever by double blind test. RESULTS The recombinant SARS-specific antigen reacted only with SARS positive sera but not with normal sera. Double blind test showed that 45 of the 46 PRNT positive sera were IFA positive with an accordance rate of 97.8%. 7 samples of sera from 4 SARS patients in acute progressive stage in Guangdong province were all IFA positive. SARS antibody could be detected since the sixth day after onset, and the titer increased from 1:40 to 1:600 on the ninth day. CONCLUSION Immunofluorescence assay is highly specific and sensitive in detection of SARS. This reagent is safe and easy to prepare.


title: Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 10. Alcohol-based antiseptics for hand disinfection and a comparison of their effectiveness with soaps.

text: Alcohol compounds are increasingly used as a substitute for hand washing in health care environments and some public places because these compounds are easy to use and do not require water or hand drying materials. However, the effectiveness of these compounds depends on how much soil (bioburden) is present on the hands. Workers in health care environments and other public places must wash their hands before using antiseptics and/or wearing gloves. However, alcohol-based antiseptics, also called rubs and sanitizers, can be very effective for rapidly destroying some pathogens by the action of the aqueous alcohol solution without the need for water or drying with towels. Alcohol-based compounds seem to be the most effective treatment against gram-negative bacteria on lightly soiled hands, but antimicrobial soaps are as good or better when hands are more heavily contaminated. Instant sanitizers have no residual effect, unlike some antimicrobial soaps that retain antimicrobial activity after the hygienic action has been completed, e.g., after hand washing. Many alcohol-based hand rubs have antimicrobial agents added to them, but each formulation must be evaluated against the target pathogens in the environment of concern before being considered for use. Wipes also are widely used for quick cleanups of hands, other body parts, and surfaces. These wipes often contain alcohol and/or antimicrobial compounds and are used for personal hygiene where water is limited. However, antiseptics and wipes are not panaceas for every situation and are less effective in the presence of more than a light soil load and against most enteric viruses.


A new serotype of infectious bronchitis virus responsible for respiratory disease in Arkansas broiler flocks.


title: Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies.

text: The spike (S) protein of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is a major antigenic determinant capable of inducing protective immunity. Recently, a small fragment on the SARS-CoV S protein (residues 318-510) was characterized as a minimal receptor-binding domain (RBD), which mediates virus binding to angiotensin-converting enzyme 2, the functional receptor on susceptible cells. In this study, we demonstrated that a fusion protein containing RBD linked to human IgG1 Fc fragment (designated RBD-Fc) induced high titer of RBD-specific Abs in the immunized mice. The mouse antisera effectively neutralized infection by both SARS-CoV and SARS pseudovirus with mean 50% neutralization titers of 1/15,360 and 1/24,737, respectively. The neutralization determinants on the RBD of S protein were characterized by a panel of 27 mAbs isolated from the immunized mice. Six groups of conformation-dependent epitopes, designated as Conf I-VI, and two adjacent linear epitopes were identified by ELISA and binding competition assays. The Conf IV and Conf V mAbs significantly blocked RBD-Fc binding to angiotensin-converting enzyme 2, suggesting that their epitopes overlap with the receptor-binding sites in the S protein. Most of the mAbs (23 of 25) that recognized the conformational epitopes possessed potent neutralizing activities against SARS pseudovirus with 50% neutralizing dose ranging from 0.005 to 6.569 microg/ml. Therefore, the RBD of SARS S protein contains multiple conformational epitopes capable of inducing potent neutralizing Ab responses, and is an important target site for developing vaccines and immunotherapeutics.


Principles of appropriate antibiotic use for treatment of acute bronchitis in adults.


title: Evaluation of Pipeline Flex delivery system for the treatment of unruptured aneurysms.

text: INTRODUCTION Refinements in endovascular technology have revolutionized the treatment of intracranial aneurysms (IAs) with the development of flow-diversion technology. The first generation of the Pipelin Embolization Device (PED) has demonstrated its safety and efficacy. However, the deployment technique was a difficult task that often led to complex maneuvers. The Pipeline Flex Embolization Device (PED Flex) is the second generation and its introduction has arrived with high expectations due to a completely redesigned delivery system that intends to overcome deployment difficulties seen in the previous generation. Areas covered: Preclinical studies, mechanism of action of flow-diverters, technical aspects and deployment system of the PED Flex, and clinical outcomes with both PED generations. Expert commentary: Flow diversion has allowed us to treat lesions that would be otherwise challenging for surgical clipping or unsuitable for other endosaccular strategies. Although the experience with PED Flex is limited, initial results suggest its safety and short-term efficacy.


title: Recent advances in targeting viral proteases for the discovery of novel antivirals.

text: The occurrence of life-threatening viral infections and the establishment of appropriate defense strategies exhibit major challenges to the disease management in our society. The unpredictable character of viral outbreaks will even be enhanced in the future due to human activities such as increasing international travel, deforestation, changes in social conditions, or influences induced by the climate change. The defense against these pathogenic agents requires preparedness, including successful drug design strategies. Viral proteases represent attractive targets for the design of anti-infective lead compounds, as in case that a viral mRNA encoding several types of proteins is recognized as a monocistronic template by the host-cell translation machinery, the presence of protease activities is required for processing the viral polyprotein precursor into structural or non-structural components essential for the formation of new virion particles. In addition, viral proteases can be involved in further processes relevant for viral replication. Numerous efforts have been made to develop potent small-molecule inhibitors of viral proteases, however, until now only a limited number reached the market. In the present contribution, functional aspects of the target proteases, their structural properties, drug design strategies, resulting inhibitors, and resistance management are reviewed and discussed by means of the four essential representative cases of HIV, HCV, SARS coronavirus, and the flaviviruses Dengue and West Nile virus.


title: Detection of a novel strain of porcine circovirus in pigs with postweaning multisystemic wasting syndrome.

text: Swine infectious agents, especially viruses, are potential public health risks associated with the use of pig organs for xenotransplantation in humans. Therefore, there is a need for better characterization of swine viruses and for the development of diagnostic tests for their detection. We report here isolation of a novel strain of porcine circovirus (PCV) from pigs with postweaning multisystemic wasting syndrome (PMWS). Affected pigs exhibited severe interstitial pneumonia and lymphoid depletion. The complete nucleotide sequence (1,768 nucleotides) of the genome of the PCV isolate was determined and compared with the sequence of the PCV strain isolated from PK-15 cells. Sequence comparison revealed significant differences between the two PCV strains, with an overall DNA homology of 76%. Two major open reading frames (ORFs) were identified. ORF1 was more conserved between the two strains, with 83% nucleotide homology and 86% amino acid homology. ORF2 was more variable, with nucleotide homology of 67% and amino acid homology of 65%. PCR and in situ hybridization demonstrated abundant viral DNA in various organs of pigs with PMWS. In situ hybridization demonstrated that this strain of PCV targets multiple organs and infects macrophages, lymphocytes, endothelial cells, and epithelial cells.


title: Comparative susceptibility of respiratory viruses to recombinant interferons-alpha 2b and -beta.

text: Intranasal recombinant interferon-alpha 2b (rIFN-alpha 2b) protects against natural colds due to rhinoviruses, but apparently not against those caused by viruses. Because rIFN-beta serine17 (rIFN-beta ser) appears less active than rIFN-alpha 2b in preventing natural rhinovirus colds, we compared the two IFNs in two in vitro assays against selected respiratory viruses. In a yield reduction assay, both IFNs had comparable activity against rhinovirus types 39 and 1A and coronavirus 229E, which were inhibited by 90% or more at IFN concentrations of 10(-11) to 10(-10) gram of protein/ml (approximately 2-20 IU/ml). Similar activities were observed with rIFN-beta ser against rhinoviruses isolated from clinical specimens. At concentrations of 10(-9) gram protein/ml, both IFNs inhibited the growth of influenza A and parainfluenza viruses, but not of adenovirus or respiratory syncytial virus in the cell culture systems tested. Thus, the different clinical protection conferred by rIFN-alpha 2b and rIFN-beta ser in studies of natural rhinovirus colds are not accounted for by differences in their in vitro activity against these viruses, and other explanations must be found.


docid: puxbcoxl

title: Lymphoid follicular cloacal inflammation associated with a novel herpesvirus in juvenile alligators (Alligator mississippiensis).

text: Multifocal hyperemic nodules and plaques associated with the cloacal mucosa of juvenile alligators (Alligator mississippiensis) at a public aquarium were investigated. Grossly, pale pink to dark red multifocal, circular lesions of varying degrees of severity were identified on the cloacal and, in males, phallus mucosa. Cloacal mucosa biopsies were obtained from 2 of the alligators. These samples were examined histologically and by polymerase chain reaction (PCR) using consensus primers targeting a conserved region of the herpesvirus polymerase gene. Microscopically, the lesions were characterized as submucosal lymphoid follicles with hyperemia and hemorrhage. No inclusion bodies were observed. Minimal to no anisokaryosis was present, and no etiologic agents were identified. Through PCR, a band consistent in size with herpesvirus was observed. Tissues showing similar clinical, histopathologic, and PCR findings were collected from animals at an alligator farm several months later. Sequencing of the PCR amplicon resulted in a 180-base pair sequence that shared 85% sequence identity with tortoise herpesvirus-1.


title: Training Physicians toward a Dignifying Approach in Adolescents' Health Care: A Promising Simulation-Based Medical Education Program.

text: BACKGROUND Human dignity has a pivotal role within the health care system. There is little experience using simulation-based medical education (SBME) programs that focus on human dignity issues in doctor-patient relationships. OBJECTIVES To describe and assess a SBME program aimed at improving physicians' competence in a dignifying approach when encountering adolescents and their parents. METHODS A total of 97 physicians participated in 8 one-day SMBE workshops that included 7 scenarios of typical adolescent health care dilemmas. These issues could be resolved if the physician used an appropriate dignifying approach toward the patient and the parents. Debriefing discussions were based on video recordings of the scenarios. The effect of the workshops on participants' approach to adolescent health care was assessed by a feedback questionnaire and on 5-point Likert score questionnaires administered before the workshop and 3 months after. RESULTS All participants completed both the pre-workshop and the feedback questionnaires and 41 (42%) completed the post-workshop questionnaire 3 months later. Practice and competence topics received significantly higher scores in post-workshop questionnaires (P < 0.001). A score of high to very high was given by 90% of physicians to the contribution of the workshop to participants understanding the dignifying approach, and by 70% to its influence on their communicative skills. CONCLUSIONS A one-day simulation-based workshop may improve physicians' communication skills and sense of competence in addressing adolescents' health care issues which require a dignifying approach toward both the adolescent patients and their parents. This dignity-focused methodology may be expanded to improve communication skills of physicians from various disciplines.


On-site quantification of human urinary albumin by a fluorescence immunoassay.


title: Ready, aye ready? Support mechanisms for healthcare workers in emergency planning: a critical gap analysis of three hospital emergency plans.

text: BACKGROUND In response to the 2003 global outbreak of severe acute respiratory syndrome (SARS), and the threat of pandemic influenza, Canadian hospitals have been actively developing and revising their emergency plans. Healthcare workers are a particularly vulnerable group at risk of occupational exposure during infectious disease outbreaks, as seen during SARS and as documented/reported in the recent National Survey of the Work and Health of Nurses (Statistics Canada, 2006). Approximately one third of Canadian nurses identified job strain and poor health, related to their work environment. Three years after SARS, this article presents a critical analysis of the gaps of three hospital pandemic influenza plans in the context of established organizational supports for healthcare workers. METHODS Hospital pandemic influenza plans were obtained from institutional representatives in three Ontario cities. Qualitative gap analysis of these plans was conducted using a checklist of 11 support categories, developed from a review of existing literature and findings from a previous study of focus groups with emergency and critical care nurses. RESULTS Support mechanisms were identified in the plans; however, gaps were evident in preparation for personal protective equipment, education and informational support, and support during quarantine. Hospital emergency planning could be more robust by including additional organizational supports such as emotional/psychological support services, delineating management responsibilities, human resources, vaccine/anti-viral planning, recognition/compensation, media strategies, and professional development. CONCLUSIONS Since the 2003 SARS outbreak, hospitals have invested in pandemic planning, as evidenced by the comprehensive plans examined here. Organizational support mechanisms for healthcare workers were included in these hospital plans; however, the gaps identified here may have serious implications for employee health and safety, and overall response during a large scale infectious disease outbreak. The authors provide a number of recommendations for consideration in infectious disease pandemic plan development to better support the healthcare workers in their roles as first responders.


title: Multiple sclerosis attacks are associated with picornavirus infections.

text: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which often follows a relapsing-remitting (RR) course with discrete attacks. MS attacks have been associated with upper respiratory infections (URIs), but the specific viruses responsible have not been identified. We studied a cohort of 16 RRMS patients experiencing URI and followed them for clinically identifiable attacks. The viral causes of 21 separate URIs were investigated using culture and polymerase chain reaction (PCR) of nasal swab specimens, and by serology. Sibleys 'at-risk' period for MS attacks, beginning two weeks before and continuing for five weeks after a URI, was used for the analysis. Seven of the nine (78%) URIs due to picornaviruses were associated with an MS attack during the at-risk period. By contrast, only two of 12 (17%) picornavirus-negative URIs were associated with an MS attack (P = 0.01). The possible role of picornaviruses in the pathogenesis of MS deserves further study.


title: On case-fatality rate: review and hypothesis.

text: The relationship between log cumulative number of patients (X) and that of deaths (Y) in an epidemic follows the equation logY = klogX - klogN(0), where k is a constant determining the slope and N(0) is the value of X when Y = 1. Diseases with k = 1 are Ebola hemorrhagic fever, avian influenza H5N1, cholera, and hand, foot, and mouth disease; those with k > 1 are the influenza H1N1 2009 pandemic in countries other than Mexico and the SARS epidemic in some countries; and those with k < 1 include the influenza H1N1 2009 pandemic in Mexico. Epidemics with k > 1 can be simulated by postulating two subpopulations (normal population [NP] and vulnerable population [VP]), where the epidemic proceeds at higher speed and at higher mortality in VP than in NP. Epidemics with k < 1 can be simulated by postulating coexisting high virulence virus (HVV) and low virulence virus (LVV), with the former being propagated at slower speed and with a higher mortality rate than the latter. An epidemic with k > 1 was simulated using parameters that are fractions of subpopulations NP or VP from the total population (f) and NP- or VP-specific patient multiplication (M) and mortality (D) rates. An epidemic with k < 1 was simulated using parameters that are fractions of HVV- or LVV-infected human populations (f), and HVV- or LVV-specific M and D.


title: Antiviral chemotherapeutic agents against respiratory viruses: where are we now and what's in the pipeline?

text: PURPOSE OF REVIEW The emergence of severe acute respiratory syndrome in late 2002 and the recent outbreaks of avian influenza in Asia are timely reminders of the ever present risks from respiratory viral diseases. Apart from influenza, there are no vaccines and very few antiviral chemotherapeutic agents available for the prevention and treatment of respiratory viral infections-the most common cause of human illness. If the current H5N1 avian influenza outbreak ever assumes the role of a pandemic, formidable technical difficulties relating to the properties of the agent, itself, will ensure that vaccines will only become available after a significant lead time and then only to a relatively small percentage of the population. The use of existing antivirals could be critical in limiting the initial spread of a pandemic, although their use in the control of epidemics caused by nonpandemic viruses has not been evaluated. It is against this background that a review of recent developments in respiratory antivirals has been undertaken. RECENT FINDINGS The late 1990s were a period of unprecedented activity in the development of new and much superior antivirals for the treatment of influenza infections. However, during the past 2 to 3 years and largely for commercial reasons, there has been a decline in interest in their further development by major drug companies. This situation may soon change with the possible advent of new pandemic viruses, and moves are afoot in several countries to consider the stockpiling of antivirals. The neuraminidase inhibitors zanamivir and oseltamivir, and the M2 inhibitors amantadine and rimantadine, remain the only options for controlling respiratory disease caused by influenza viruses, although the latter two could not be used against very recent H5N1 strains. There are several other neuraminidase inhibitors in development. Compounds with activity against other respiratory viruses, notably rhinoviruses, are also in development, many based on a newer knowledge of viral protein structure and function (rational drug design). SUMMARY The following is an overview of recent papers on the further development of neuraminidase inhibitors against influenza viruses and on recent development of newer antivirals against RSV and rhinoviruses. Where possible, comparisons are made with existing antivirals. For considerations of space, this review has been structured around stages in the replication cycle of significant respiratory viruses that have been traditionally used as targets for inhibition.


title: Antegrade cerebral perfusion at 25 °C for arch reconstruction in newborns and children preserves perioperative cerebral oxygenation and serum creatinine.

text: BACKGROUND Antegrade cerebral perfusion (ACP) typically is used with deep hypothermia for cerebral protection during aortic arch reconstructions. The impact of ACP on cerebral oxygenation and serum creatinine at a more tepid 25 °C was studied in newborns and children. METHODS Between 2010 and 2014, 61 newborns and children (<5 years old) underwent aortic arch reconstruction using moderate hypothermia (25.0±0.9 °C) with ACP and a pH-stat blood gas management strategy. These included 44% Norwood-type operations, 30% isolated arch reconstructions, and 26% arch reconstructions with other major procedures. Median patient age at surgery was 9 days (range, 3 days-4.7 years). Cerebral oxygenation (NIRS) was monitored continuously perioperatively for 120 hours. Serum creatinine was monitored daily. RESULTS Median cardiopulmonary bypass (CPB) and cross clamp times were 181 minutes (range, 82-652 minutes) and 72 minutes (range, 10-364 minutes), respectively. ACP was performed at a mean flow rate of 46±6 mL/min/kg for a median of 48 minutes (range, 10-123 minutes). Cerebral and somatic NIRS were preserved intraoperatively and remained at baseline postoperatively during the first 120 hours. Peak postoperative serum creatinine levels averaged 0.7±0.3 mg/dL for all patients. There were 4 (6.6%) discharge mortalities. Six patients (9.8%) required ECMO support. Median postoperative length of hospital and intensive care unit (ICU) stay were 16 days(range, 4-104 days) and 9 days (range, 1-104 days), respectively. Two patients (3.3%) received short-term peritoneal dialysis for fluid removal, and none required hemodialysis. Three patients (4.9%) had an isolated seizure which resolved with medical therapy, and none had a neurologic deficit or stroke. CONCLUSIONS ACP at 25 °C preserved perioperative cerebral oxygenation and serum creatinine for newborns and children undergoing arch reconstruction. Early outcomes are encouraging, and additional study is warranted to assess the impact on late outcomes.


title: Multi-state epidemic processes on complex networks.

text: Infectious diseases are practically represented by models with multiple states and complex transition rules corresponding to, for example, birth, death, infection, recovery, disease progression, and quarantine. In addition, networks underlying infection events are often much more complex than described by meanfield equations or regular lattices. In models with simple transition rules such as the SIS and SIR models, heterogeneous contact rates are known to decrease epidemic thresholds. We analyse steady states of various multi-state disease propagation models with heterogeneous contact rates. In many models, heterogeneity simply decreases epidemic thresholds. However, in models with competing pathogens and mutation, coexistence of different pathogens for small infection rates requires network-independent conditions in addition to heterogeneity in contact rates. Furthermore, models without spontaneous neighbor-independent state transitions, such as cyclically competing species, do not show heterogeneity effects.


title: [CT imaging features of patients with different clinical types of COVID-19].

text: OBJECTIVE To investigate the CT findings of patients with different clinical types of coronavirus disease 2019 (COVID-19). METHODS A total of 67 patients diagnosed as COVID-19 by nucleic acid testing were collected and divided into 4 groups according to the clinical stages based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6). The CT imaging characteristics were analyzed among patients with different clinical types. RESULTS Among 67 patients, 3(4.5%) were mild, 35 (52.2%) were moderate, 22 (32.8%) were severe, and 7(10.4%) were critical ill. No significant abnormality in chest CT imaging in mild patients. The 35 cases of moderate type included 3 (8.6%) single lesions, the 22 cases of severe cases included 1 (4.5%) single lesion and the rest cases were with multiple lesions. CT images of moderate patients were mainly manifested by solid plaque shadow and halo sign (18/35, 51.4%); while fibrous strip shadow with ground glass shadow was more frequent in severe cases (7/22, 31.8%). Consolidation shadow as the main lesion was observed in 7 cases, and all of them were severe or critical ill patients. CONCLUSIONS CT images of patients with different clinical types of COVID-19 have characteristic manifestations, and solid shadow may predict severe and critical illness.


title: Patients' perceptions of nasopharyngeal aspiration in the emergency department of a teaching hospital in Hong Kong.

text: Nasopharyngeal aspiration (NPA) is the preferred method for collecting specimens for viral culture in patients with respiratory tract infection. As virus identification may influence admission and treatment decisions, it is important to perform NPA in the emergency department. The test may be uncomfortable and poorly tolerated. This prospective study investigated patients' perceptions of NPA. Patients in the emergency department with upper respiratory tract infection undergoing NPA between 9 March 2005 and 12 August 2005 were included. 86 patients (mean (SD) age 47 (23) years; 49 women) were recruited. 22 (26%) patients complained that NPA was very uncomfortable, 59 (69%) reported that it was mildly uncomfortable and 5 (6%) patients reported no discomfort. On a 10-point scale, the median discomfort score was 4. 29 (34%) patients stated that NPA was more uncomfortable than blood taking, 19 (22%) patients felt that both were similar and 38 (44%) patients felt that NPA was less uncomfortable (p value not significant). NPA performed in the emergency department is well tolerated and should be considered in emergency departments when results may influence patient management.


title: Environmental factors on the SARS epidemic: air temperature, passage of time and multiplicative effect of hospital infection.

text: The study sought to identify factors involved in the emergence, prevention and elimination of severe acute respiratory syndrome (SARS) in Hong Kong during 11 March to 22 May 2003. A structured multiphase regression analysis was used to estimate the potential effects of weather, time and interaction effect of hospital infection. In days with a lower air temperature during the epidemic, the risk of increased daily incidence of SARS was 18.18-fold (95% confidence interval 5.6-58.8) higher than in days with a higher temperature. The total daily new cases might naturally decrease by an average of 2.8 patients for every 10 days during the epidemic. The multiplicative effect of infected hospital staff with patients in an intensive care unit (ICU) and the proportion of SARS patients in ICUs might respectively increase the risk of a larger SARS epidemic in the community. The provision of protective gear in hospitals was also a very important factor for the prevention of SARS infection. SARS transmission appeared to be dependent on seasonal temperature changes and the multiplicative effect of hospital infection. SARS also appeared to retreat naturally over time.


title: Office pediatrics: current issues in lower respiratory infections in children.

text: PURPOSE OF REVIEW Recent estimates indicate that 1.9 million children worldwide die each year from acute respiratory illnesses, many of which are lower respiratory infections (LRIs). Global threats from indoor and outdoor air pollution, urban crowding, biologic weapons, and worldwide rapid transportation complicate our efforts to reduce the impact of LRI disease in children. As new strategies are developed to limit the spread of LRI disease in children, existing pathogens become more complex to treat and newer pathogens emerge as causes of clinical disease. Most LRI disease is managed in outpatient settings and remains a challenge to those who care for children. RECENT FINDINGS Atypical pathogens (notably mycoplasma pneumoniae) are now known to cause a wide spectrum of disease, and with more extensive complications than previously recognized. Available data suggest a rapid increase in S. pneumoniae resistance to penicillin and macrolides in many cases of community acquired pneumonia, which has resulted in shifts in outpatient (and inpatient) antibiotic treatment regimens. Human metapneumovirus (HMPV) is now recognized to cause LRI illness similar to respiratory syncytial virus (RSV) in infants and children. General strategies for the prevention of influenza infection are expanded to include many infants and young children, and are projected to significantly reduce morbidity and mortality from this key LRI pathogen. SUMMARY The spectrum of LRI pathogens--and the clinical illnesses caused by them--continues to change. Innovations in immunotherapy and vaccines will be instrumental to reducing the burden of LRI morbidity in infants and children worldwide in the future.


Lung function and low birth weight.


The health of female sex workers in Hong Kong: do we care?