title: The use of energy devices for thyroid surgical procedures. Harmonic Focus versus Biclamp 150.

text: BACKGROUND Thyroidectomy is the most frequently performed endocrine surgery, and in recent years, the surgical instruments and techniques used in this surgery have greatly evolved. New devices are created to facilitate dissection, haemostasis increasing the intraoperative cost. MATERIAL AND METHOD We prospectively examined patients undergoing to traditional thyroidectomy using reusable vs disposable devices (BiClamp 150, ERBE ® - group A vs. Harmonic Focus, ETHICON® - group B). The patients were treated for benign and malignant diseases from two experienced surgeons. The two groups were separated based on age, sex, skin-to-skin operative time, the number of parathyroid glands identified by the surgeon during the operation, preand post-operative serum calcium levels evaluated with PTH until 24 hours after surgery, the mean hospital stay, the evaluation of the content of the drainages at 6 hours and 24 hours, and the thyroid gland volume calculated via ultrasound preoperatively. The patients were asked to complete a form at 24 hours post-op to self-evaluate dysphagia to liquids and pain on a scale from 0 to 10. RESULTS The patients analysed were 80 pts. Analysis of the data showed no significant differences between the groups with respect to age, (p = 0:48), or gender, 9 males and 31 females in group A and 8 males and 32 females in group B.The thyroid volume (in ml), calculated on the basis of preoperative ultrasonography, was 43.89 ± 37.10 in group A vs. 54.54 ± 51.92 in group B (p = 0.35). The skin-to-skin operative time was equal to 50.16 ± 10.43 min.vs. 52.39 ± 11:54 min.(p = 0.36) in groups A and B, respectively. No statistically significant differences in pre e postoperative calcium levels. The amount of drainage at 6 hours after surgery was 16.63 ± 15.24ml. in group A and 23.72 ± 21.93ml. in group B (p = 0.07). At 24 hours after surgery, the amount was 57.84 ± 32.56ml. in group A and 66.79 ± 39.94ml. in group B (p = 0.28). For group A and group B, we analysed dysphagia for liquids on a scale from 0 to 10 (4.5 ± 2.35 vs. 4.18 ± 2.4, p = 0.48, respectively), alterations in patients' tone of voice (1.97 ± 2.51 vs. 1.43 ± 0:48, p = 0.29, respectively), and postoperative pain at 24 hours after surgery (2.76 ± 1.99 vs. 2.68 ± 2.12, p = 0.87, respectively). The average cost for group A was equal to € 25 × 40 = 1000 vs. € 450 × 40 = 18000 for Group B. The hospital stay in days was equal to 1.70 ± 0.46 (Group A) vs. 1.66 ± 0.53 (Group B) (p = 0.69). CONCLUSIONS One limitation of the current study is its small sample size. Both devices are effective and safe for total thyroidectomy because they have similar effects on the operative time, postoperative bleeding and patient outcomes in endocrine experienced surgical team. On the other hand, in a time of the spending review and the standardisation of surgical techniques to ensure the highest quality of services offered, the BiClamp is a viable alternative tool with a high security standard and low cost that offers significant savings to the health care system. KEY WORDS Energy devices, Health care, Thyroidectomy.


docid: nofswvni

title: Enzymatic defects of the nsP2 proteins of Semliki Forest virus temperature-sensitive mutants.

text: We have analyzed the biochemical consequences of mutations that affect viral RNA synthesis in Semliki Forest virus temperature-sensitive (ts) mutants. Of the six mutations mapping in the multifunctional replicase protein nsP2, three were located in the N-terminal helicase region and three were in the C-terminal protease domain. Wild-type and mutant nsP2s were expressed, purified, and assayed for nucleotide triphosphatase (NTPase), RNA triphosphatase (RTPase), and protease activities in vitro at 24 degrees C and 35 degrees C. The protease domain mutants (ts4, ts6, and ts11) had reduced protease activity at 35 degrees C but displayed normal NTPase and RTPase. The helicase domain mutation ts1 did not have enzymatic consequences, whereas ts13a and ts9 reduced both NTPase and protease activities but in different and mutant-specific ways. The effects of these helicase domain mutants on protease function suggest interdomain interactions within nsP2. NTPase activity was not directly required for protease activity. The similarities of the NTPase and RTPase results, as well as competition experiments, suggest that these two reactions utilize the same active site. The mutations were also studied in recombinant viruses first cultivated at the permissive temperature and then shifted up to the restrictive temperature. Processing of the nonstructural polyprotein was generally retarded in cells infected with viruses carrying the ts4, ts6, ts11, and ts13a mutations, and a specific defect appeared in ts9. All mutations except ts13a were associated with a large reduction in the production of the subgenomic 26S mRNA, indicating that both protease and helicase domains influence the recognition of the subgenomic promoter during virus replication.


Immune mechanisms in inflammatory polyneuropathy.


Coronaviruses: structure and genome expression.


title: [Respiratory tract viruses].

text: The respiratory tract is the site of entrance of many viruses. However, not all of them cause symptomatic respiratory infections. In the past the clinical significance of some viruses was underestimated. Viruses leading to population-wide epidemics like influenzavirus or to nosocomial outbreaks like respiratory syncytial virus or SARS-associated coronavirus have a great impact on public health and the respective preventive measures are of paramount importance. The advent of new diagnostic tools led to discoveries and additional information about some "banal" viruses causing severe diseases in special hosts such as infants and immunosuppressed patients. In addition new viral pathogens were discovered and found to cause respiratory infections, metapneumovirus and SARS-associated coronavirus being the most important ones.


title: Evolution of RNA viruses.

text: These arguments lead to the suggestion that four independent evolutionary lines exist within the general group of RNA viruses. These are positive strand viruses, negative strand viruses, double stranded viruses, and retroviruses. Three of the viral systems may well have shared genes but the double-stranded RNA viruses appear to represent a very different evolutionary line.


title: Is systems biology the key to preventing the next pandemic?

text: Sporadic outbreaks of epizootics including SARS coronavirus and H5N1 avian influenza remind us of the potential for communicable diseases to quickly spread into worldwide epidemics. To confront emerging viral threats, nations have implemented strategies to prepare for pandemics and to control virus spread. Despite improved surveillance and quarantine measures, we find ourselves in the midst of a H1N1 influenza pandemic. Effective therapeutics and vaccines are essential to protect against current and future pandemics. The best route to effective therapeutics and vaccines is through a detailed and global view of virus-host interactions that can be achieved using a systems biology approach. Here, we provide our perspective on the role of systems biology in deepening our understanding of virus-host interactions and in improving drug and vaccine development. We offer examples from influenza virus research, as well as from research on other pandemics of our time - HIV/AIDS and HCV - to demonstrate that systems biology offers one possible key to stopping the cycle of viral pandemics.


title: Ethical and legal challenges posed by severe acute respiratory syndrome: implications for the control of severe infectious disease threats.

text: The appearance and spread of severe acute respiratory syndrome (SARS) on a global level raised vital legal and ethical issues. National and international responses to SARS have profound implications for 3 important ethical values: privacy, liberty, and the duty to protect the public's health. This article examines, through legal and ethical lenses, various methods that countries used in reaction to the SARS outbreak: surveillance and contact tracing, isolation and quarantine, and travel restrictions. These responses, at least in some combination, succeeded in bringing the outbreak to an end. The article articulates a set of legal and ethical recommendations for responding to infectious disease threats, seeking to reconcile the tension between the public's health and individual rights to privacy, liberty, and freedom of movement. The ethical values that inform the recommendations include the precautionary principle, the least restrictive/intrusive alternative, justice, and transparency. Development of a set of legal and ethical recommendations becomes even more essential when, as was true with SARS and will undoubtedly be the case with future epidemics, scientific uncertainty is pervasive and urgent public health action is required.


title: Identification of a feline coronavirus type I strain from a cat with feline infectious peritonitis by RT-pCR and phylogenetic analysis.

text: A case of feline infectious peritonitis (FIP) in an 11-month-old European shorthair cat is reported. The infected cat displayed loss of weight, respiratory distress, ascitis, anemia and died within 15 days after the first appearance of clinical signs. Lesions typical of a mixed form (effusive and non-effusive) of FIP were observed and by RT-PCR a feline coronavirus (FCoV) type I strain was detected in several tissues. The RT-PCR results were confirmed by sequence analysis of the amplified products. Phylogeny carried out on fragments of the M and S genes showed that the FCoV strain segregates with typical type I FCoVs.


Human embryonic stem cell-derived fibroblastic and epitheloid lineages as xeno-free support?


title: Evaluation of advanced reverse transcription-PCR assays and an alternative PCR target region for detection of severe acute respiratory syndrome-associated coronavirus.

text: First-generation reverse transcription-PCR (RT-PCR) assays for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) gave false-negative results in a considerable fraction of patients. In the present study, we evaluated two second-generation, replicase (R) gene-based, real-time RT-PCR test kits--the RealArt HPA coronavirus LC kit (Artus, Hamburg, Germany) and the LightCycler SARS-CoV quantification kit (Roche, Penzberg, Germany)--and a real-time RT-PCR assay for the nucleocapsid (N) gene. Detecting the N-gene RNA might be advantageous due to its high abundance in cells. The kits achieved sensitivities of 70.8% (Artus) and 67.1% (Roche) in 66 specimens from patients with confirmed SARS (samples primarily from the upper and lower respiratory tract and stool). The sensitivity of the N-gene assay was 74.2%. The differences in all of the sensitivities were not statistically significant (P = 0.680 [analysis of variance]). Culture cells initially contained five times more N- than R-gene RNA, but the respective levels converged during 4 days of virus replication. In clinical samples the median concentrations of R- and N-gene RNA, respectively, were 1.2 x 10(6) and 2.8 x 10(6) copies/ml (sputum and endotracheal aspirates), 4.3 x 10(4) and 5.5 x 10(4) copies/ml (stool), and 5.5 x 10(2) and 5.2 x 10(2) copies/sample (throat swabs and saliva). Differences between the samples types were significant but not between the types of target RNA. All (n = 12) samples from the lower respiratory tract tested positive in all tests. In conclusion, the novel assays are more sensitive than the first-generation tests, but they still do not allow a comprehensive ruling out of SARS. Methods for the routine sampling of sputum without infection risk are needed to improve SARS RT-PCR.


title: Making better use of technological advances to meet stakeholder needs.

text: Controlling transboundary diseases requires an inclusive and collaborative international approach. Decisions should be taken (and seen to be taken) on advice from multidisciplinary teams of scientists and representatives from all groups significantly affected by the disease (the 'stakeholders'). Changes in trade and travel mean that, unless a new model is developed for disease prevention, there is a real possibility that transboundary animal diseases will become increasingly difficult to control. The traditional government approach of dealing almost exclusively with the commercial sector of the livestock industry is no longer sufficient, and new ways must be found to include all sectors, including 'grey' husbandry (fragmented, disparate groups whose involvement with animals may range from the legal and responsible to the unsanctioned and/or illegal). The increasing convergence of human and animal health issues makes it imperative to make the best possible use of new tools. The particular challenges confronting veterinary science are: preventing the introduction of disease, rapidly identifying disease and controlling epidemics. This paper focuses on the United Kingdom to investigate the inadequacies of current approaches, identify needs, offer recommendations and propose a new approach to disease control, which emphasises global considerations. The objectives are: better participation across the entire sector, better communication, better science and better decision-making, all of which should lead to better security from disease.


title: Identification of group B rotaviruses with short genome electropherotypes from adult cows with diarrhea.

text: Two field strains (BB-RVLV and KD) of group B rotaviruses from adult dairy cows with diarrhea displayed short genome electropherotypes. Gnotobiotic calves inoculated with fecal filtrates of each group B rotavirus developed diarrhea, and only group B rotaviruses or antigens were detected in the feces by immunoelectron microscopy and in intestinal epithelial cells by immunofluorescent staining, respectively. The feces or intestinal contents of the cows and inoculated calves were negative for group A and C rotaviruses by enzyme-linked immunosorbent assay, immunoelectron microscopy, or cell culture immunofluorescence assays. Comparison of the genome electropherotypes of the calf-passaged BB-RVLV and KD strains with the original samples and reference bovine group A, B, and C rotaviruses revealed conservative of their short-genome electropherotypes and double-stranded RNA migration patterns characteristics of group B rotaviruses. To our knowledge, our previous study (L.J. Saif, K.V. Brock, D.R. Redman, and E.M. Kohler, Vet. Rec. 128:447-449, 1991) and this report are the first description of bovine group B rotaviruses (in a mixed infection with bovine coronavirus or singly in fecal contents) in adult cows with diarrhea and this is the first report of short-genome electropherotypes among group B rotaviruses.


Fascination for vaccination: about achievements and challenges in the vaccine world.


title: [Preliminary report on the Covid-19 outbreak in Valle d'Aosta dialysis centers].

text: Valle d'Aosta, Italy's smallest region, faced a Covid-19 epidemic trend of absolute relevance. In line with data concerning the local general population, the predominance of the illness among uremic patients has been high. The authors report here preliminary data on the spread of this disease within the region and on the clinical trend of the infected patients who needed to be hospitalised.


docid: lrcrkjsl

title: Molecular epidemiology of infectious diseases: a case for increased surveillance.


Dengue virus serotype 3, Karachi, Pakistan.


title: Direct comparison between cerebral oximetry by INVOS(TM) and EQUANOX(TM) during cardiac surgery: a pilot study.

text: INTRODUCTION Several near-infrared spectroscopy oximeters are commercially available for clinical use, with lack of standardization among them. Accordingly, cerebral oxygen saturation thresholds for hypoxia/ischemia identified in studies conducted with INVOS(TM) models do not necessarily apply to other devices. In this study, the measurements made with both INVOS(TM) and EQUANOX(TM) oximeters on the forehead of 10 patients during conventional cardiac surgery are directly compared, in order to evaluate the interchangeability of these two devices in clinical practice. METHODS Cerebral oxygen saturation measurements were collected from both INVOS(TM) 5100C and EQUANOX(TM) 7600 before anesthetic induction (baseline), two minutes after tracheal intubation, at cardiopulmonary bypass onset/offset, at aortic cross-clamping/unclamping, at the end of surgery and whenever at least one of the two devices measured a reduction in cerebral oxygen saturation equal to or greater than 20% of the baseline value. Bland-Altman analysis was used to compare the bias and limits of agreement between the two devices. RESULTS A total of 140 paired measurements were recorded. The mean bias between INVOS(TM) and EQUANOX(TM) was -5.1%, and limits of agreement were ±16.37%. Considering the values as percent of baseline, the mean bias was -1.43% and limits of agreement were ±16.47. A proportional bias was observed for both absolute values and changes from baseline. CONCLUSIONS INVOS(TM) and EQUANOX(TM) do not seem to be interchangeable in measuring both absolute values and dynamic changes of cerebral oxygen saturation during cardiac surgery. Large investigations, with appropriate design, are needed in order to identify any device-specific threshold.


Authors' Reply. MERS-CoV, surgical mask and N95 respirators.


[BCG versus COVID-19?]


title: Asthma and viruses: is there a relationship?

text: Asthma is a multifactorial disease in which many factors play a role in its development and exacerbations. Viral infections are known to be the main cause of asthmatic exacerbations and are often the first manifestation of asthma in preschool age. However, there is much evidence suggesting a role of viral infections even in asthma development. Respiratory Syncytial Virus (RSV). has been first associated with an increased risk to develop asthma, but recently new viruses have been proposed to be involved in asthma pathogenesis. Further studies will be needed to demonstrate a causative role of viral infections in asthma development, in order to implement preventive strategies in high-risk children.


title: Evaluation of Drain Amylase Level after Pancreaticoduodenectomy with Special Reference to Delayed Pancreatic Fistula.

text: Postoperative pancreatic fistula (PF) is a relatively frequent and occasionally fatal complication of pancreatoduodenectomy (PD). Several risk factors for PF have been reported, including high drain amylase level (D-AMY). Among the 140 consecutive patients who underwent PD, we analyzed 110 cases with D-AMY measurements over time after PD. According to the D-AMY change, we divided patients into five patterns and defined delayed PF cases. We analyzed clinical characteristics, including serum amylase and D-AMY, and examined the correlation between the period of drain insertion and PF grade. In 15 delayed PF cases, 12 cases were grade B or C, pancreatic cancer was less frequent, pancreatic ducts were smaller, and soft pancreas texture was more commonly observed. The D-AMY on postoperative day (POD) 1 was higher in cases of delayed PF compared with non-PF cases (P < 0.0001). In 28 cases with drain removal before POD 7, grade B or C PF was not observed afterward. The average D-AMY on POD 1 in cases with drain removal before POD 1 was significantly lower than in delayed PF cases. Although further studies are required to determine the most appropriate timing of drain removal, it is thought that intra-abdominal drains should be removed within seven days of PD in cases without signs of PF. On the other hand, delayed PF should be considered in cases of soft pancreas texture and/or high D-AMY on POD 1, even if D-AMY levels are low on POD 3 or decreasing on POD 5.


title: Genome-wide detection of polymorphisms at nucleotide resolution with a single DNA microarray.

text: A central challenge of genomics is to detect, simply and inexpensively, all differences in sequence among the genomes of individual members of a species. We devised a system to detect all single-nucleotide differences between genomes with the use of data from a single hybridization to a whole-genome DNA microarray. This allowed us to detect a variety of spontaneous single-base pair substitutions, insertions, and deletions, and most (>90%) of the approximately 30,000 known single-nucleotide polymorphisms between two Saccharomyces cerevisiae strains. We applied this approach to elucidate the genetic basis of phenotypic variants and to identify the small number of single-base pair changes accumulated during experimental evolution of yeast.


Artificial intelligence in prediction of mental health disorders induced by the COVID-19 pandemic among health care workers.


title: Correlation of the virulence of CSFV with evolutionary patterns of E2 glycoprotein.

text: Infection with classical swine fever virus (CSFV) is costly to the livestock industry. Several genomic sequences including velogenic strains and low virulent strains have been identified. However, the reasons for the virulence of the virus have remained unclear. Based on selective pattern and pressure strength, we classified all genes of CSFV into three classes. Among these genes, the E2 gene was under the strongest positive selection. Based on the analysis of 85 representative E2 gene sequences, the location and intensity of positive selection in CSFV isolates from group one and group two were identified. These results suggest that these two groups employ evolutionary difference. Moreover, the mutations, potentially driven by positive selection, can be correlated with the virulence of CSFV by altering the conformation and function of E2 and/or changing its glycosylation pattern. Based on these results, a model for the evolution of virulence of CSFV is proposed. The results provide a link between epidemiology and the gene function of CSFV, and may shed light on the molecular mechanism underlying the variation of CSFV virulence.


title: Localization of swine influenza virus in naturally infected pigs.

text: Swine influenza virus (SIV) RNA and antigen were detected in 15 naturally infected pigs by in situ hybridization using a nonradioactive digoxigenin-labeled cDNA probe and by immunohistochemistry using an influenza virus H1N1-specific monoclonal antibody. A 582-base pair cDNA probe for viral RNA encoding the nucleocapsid protein of SIV type A H1N1 strain was generated by the reverse transcription polymerase chain reaction. In situ hybridization and immunohistochemistry gave similar results for serial sections from each of 15 lung samples. Positive cells typically exhibited a dark brown (in situ hybridization) or red (immunohistochemistry) reaction product in the nucleus and cytoplasm without background staining. A strong positive signal for both in situ hybridization and immunohistochemistry was detected mainly in the bronchial and bronchiolar epithelial cells. A less intense signal was detected in the interstitial and alveolar macrophages. Simultaneous detection of hybridization and immunohistochemical signals on serial sections provided evidence that SIV had replicated in positive cells. The in situ hybridization technique developed in this study was useful for the detection of SIV RNA in tissues taken from naturally infected pigs and may be a valuable technique for studying the pathogenesis of SIV infection.


title: Monoclonal antibodies specific to yellow-head virus (YHV) of Penaeus monodon.

text: Monoclonal antibodies specific to 22, 67 and 135 kDa proteins of yellow-head virus (YHV) were produced from a mouse immunized with partially purified YHV isolated from the haemolymph of experimentally YHV-infected Penaeus monodon. Four groups of monoclonal antibodies were identified. One group of antibodies bound only to native protein of YHV while the others were specific to 135, 67 and 22 kDa proteins in both native and denatured forms. All antibodies could be used to detect YHV infection by means of dot blot and immunohistochemistry. However, antibodies specific to the 22 kDa protein gave the best immunohistochemistry results in terms of intensity and sharpness of staining.


Intensive care ventilators.


title: Pathogen spillover in disease epidemics.

text: In field experiments manipulating generalist pathogens and host community composition, the presence of a highly susceptible reservoir species drove disease dynamics in multiple nonreservoir species, sometimes decreasing their abundance through apparent competition. The dynamics of generalist pathogens in multispecies host communities remain a major frontier for disease ecology. Of particular interest are how host community structure controls pathogen transmission and how disease spread feeds back to influence the host community. Pathogen spillover occurs when epidemics in a host population are driven not by transmission within that population but by transmission from a reservoir population. Here we review examples of spillover in pathogens infecting humans, domesticated animals, and crops, noting that most empirical evidence for spillover results from nonmanipulative, observational studies. We then present results from two field experiments utilizing an experimentally tractable model system of annual wild grasses and a generalist virus, the barley yellow dwarf virus. In these experiments, the presence of a highly susceptible reservoir species, Avena fatua (wild oats), greatly increased pathogen prevalence in several other species. This result demonstrates pathogen spillover and illustrates the crucial role of host community structure in controlling the dynamics of generalist pathogens. Further, pathogen spillover from A. fatua decreased the abundance of two other host species through pathogen-mediated apparent competition. Thus, our results provide experimental support for theoretical predictions of strong feedbacks between host community structure and generalist disease dynamics.


title: Canine myocilin is associated with lipid modified by palmitic acid.

text: PURPOSE Myocilin, the product of the GLC1A locus in humans, has been associated with primary open angle glaucoma (POAG). Mutations in myocilin exon 3 correlate with age of onset and severity of POAG. Myocilin has been under investigation in experimentally induced glaucoma in rats, mice, and monkeys, however no animal model of inherited POAG exists except in beagles. Our aim was to determine whether canine myocilin more closely resembles human myocilin than does myocilin from other species. METHODS Canine myocilin was cloned and sequenced from beagle ocular tissues and Madin-Darby Canine Kidney (MDCK) cells, a well characterized canine cell line. Immunohistochemistry was performed on beagle tissues and cultured canine ocular primary cells. RT-PCR was employed to analyze genes expressed by tissues and cells. Myocilin protein synthesized by MDCK and canine optic nerve head cells (ONH) was analyzed by metabolic radioisotope labeling. Immunoprecipitation, enzymatic digestion, and Triton X-114 phase separation were performed to determine the carbohydrate content and the hydrophobicity of canine myocilin, respectively. RESULTS Canine ONH astrocytes cultured from a beagle eye expressed myocilin and markers of type 1B astrocytes observed also in human ONH cells in culture. The sequence of canine myocilin showed close similarity with the human sequence but lacked the additional upstream coding region found only in human and rat. Myocilin was labeled with (3)H palmitic acid. This label co-eluted with (35)S label in hydroxylapatite chromatography despite purification by phase separation in Triton X-114, immunoprecipitation with myocilin-specific sera, and denaturing conditions of heat, SDS, and reducing agent. CONCLUSIONS Canine myocilin revealed no striking sequence differences from myocilin of other species. Mutations in myocilin of glaucomatous beagles may suggest a similar pattern of involvement in inherited POAG. This represents the first report of lipid associated with the myocilin protein. Many lipid-modified proteins reside in lipid rafts. This modification of myocilin with lipids supports the unusual secretion properties and may suggest a function of myocilin in sorting, cell signaling and communication between the extracellular matrix and the cell membranes.


docid: lifwohea

title: Evaluation of a new rapid molecular diagnostic system for Plasmodium falciparum combined with DNA filter paper, loop-mediated isothermal amplification, and melting curve analysis.

text: Falciparum malaria is a fatal infection without immediate diagnosability or treatment. There are shortages of clinicians and examiners skilled in the treatment of malaria in non-endemic countries, including Japan. This study was performed to evaluate a novel rapid molecular diagnostic system consisting of loop-mediated isothermal amplification (LAMP) combined with DNA filter paper (FTA card) and melting curve analysis. Combining LAMP with melting curve analysis enabled diagnosis of Plasmodium falciparum more accurately with relative ease. FTA cards could be used to clarify problems regarding storage, infectivity, and transportation. The LAMP assay was carried out at a constant temperature of 63 degrees C for 90 min. The diagnostic system (malaria-LAMP) accurately diagnosed malaria (47 samples from Thailand and 50 from Zimbabwe) with 97.8% sensitivity and 85.7% specificity as compared with microscopic methods, indicating the usefulness of this combined system.


docid: bgroulnl

title: Pancreatic Cancer During COVID-19 Pandemic: Treat or Not to Treat?

text: Pancreatic cancer is a very aggressive disease and survival remains dismal even with treatment. Currently, management of patients with pancreatic cancer has been complicated by the ongoing COVID-19 pandemic. Medical oncologists face the dilemma of whether to treat or to not treat these patients who are at high-risk of complications and even death from COVID-19. No current guidelines are available and our limited experience at this time makes it more difficult to manage these patients. Although we have general strategies available from experience in Italy, we need more treatment specific strategies to help mitigate risks of complications and toxicities from chemotherapy in order to protect our patients from COVID-19 as much as possible.


title: [Clinical experience of high-flow nasal cannula oxygen therapy in severe COVID-19 patients].

text: Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.


Outpatient Teledermatology Implementation During the COVID-19 Pandemic: Challenges and Lessons Learned.


title: Kawasaki disease.

text: Kawasaki disease (KD) is a common vasculitic disorder usually seen in children below 5 years of age. The disease can present with protean clinical manifestations which include high grade fever (for at least 5 days), rash, redness of the lips and a typical strawberry tongue, cervical lymph node enlargement (often unilateral), swelling over the hands/feet and, later a characteristic peripheral desquamation over the fingers and toes. These clinical features appear sequentially and the findings may change from day-to-day. Thus, all these features may not be seen together at any one point of time. The diagnosis rests on the recognition of this characteristic temporal sequence of clinical events, none of which are, by themselves, pathognomonic. Establishing a diagnosis of KD may be further complicated by the occurrence of several other, seemingly unrelated, clinical features. These include irritability, neck stiffness, sterile pyuria, pneumonitis, hydrops of the gallbladder and hepatitis among many others. There is no laboratory test that can help in confirming a diagnosis of KD. Left untreated, up to 20% of children with KD can develop coronary aneurysms with catastrophic long term sequelae. It is important to diagnose KD in the first 10 days of the illness so that appropriate therapy with intravenous immunoglobulin and aspirin can be Initiated. All paediatricians, and physicians looking after children, need to be aware of this condition which is now being increasingly recognized in India.


Northern Ireland disease surveillance, January to March 2012.


title: Reported HIV status of tuberculosis patients--United States, 1993-2005.

text: Knowing the human immunodeficiency virus (HIV) status of tuberculosis (TB) patients is essential to optimal patient management. TB is an acquired immunodeficiency syndrome (AIDS)-defining opportunistic condition. Patients with both TB and HIV infection are five times more likely to die during anti-TB treatment than patients who are not HIV infected (CDC, unpublished data, 2003). HIV infection is the greatest known risk factor for progression from latent TB infection to TB disease. In the United States, after TB exposure and infection, HIV-infected persons who do not receive appropriate treatment progress to TB disease over 5 years at a rate 10 times greater than that for persons not infected with HIV. In 1989, CDC recommended that all TB patients be offered HIV testing and, in 2006, called for routine HIV screening of all TB patients after the patient is notified that testing will be performed, unless the patient declines (opt-out screening). In addition to enabling optimal patient management, knowing the HIV status (i.e., positive or negative) of TB patients helps public health agencies to identify HIV-infected contacts of TB patients. Highly active antiretroviral therapy (HAART) can reduce the progression to TB disease, TB relapse, and death. To assess reported HIV status of TB patients and selected characteristics of TB patients with HIV infection, CDC analyzed data from the U.S. National TB Surveillance System for the period 1993-2005. This report summarizes the results of that analysis, which indicated that 1) reporting of HIV status among TB patients increased from 35% in 1993 to 68% in 2003, 2) HIV status of 31% of TB patients was unknown in 2005, 3) 9% of TB patients were HIV positive in 2005, and 4) groups of TB patients at greater risk for HIV infection included injection-drug users (IDUs), noninjection-drug users (NIDUs), homeless persons, non-Hispanic blacks, correctional-facility inmates, and alcohol abusers. Increased promotion of routine HIV testing and rapid HIV tests might increase acceptability of testing, which would allow health-care providers to know the HIV status of a greater percentage of TB patients and enable them to provide optimal care.


title: China's public health-care system: facing the challenges.

text: The severe acute respiratory syndrome (SARS) crisis in China revealed not only the failures of the Chinese health-care system but also some fundamental structural deficiencies. A decentralized and fragmented health system, such as the one found in China, is not well-suited to making a rapid and coordinated response to public health emergencies. The commercial orientation of the health sector on the supply-side and lack of health insurance coverage on the demand-side further exacerbate the problems of the under-provision of public services, such as health surveillance and preventive care. For the past 25 years, the Chinese Government has kept economic development at the top of the policy agenda at the expense of public health, especially in terms of access to health care for the 800 million people living in rural areas. A significant increase in government investment in the public health infrastructure, though long overdue, is not sufficient to solve the problems of the health-care system. China needs to reorganize its public health system by strengthening both the vertical and horizontal connections between its various public health organizations. China's recent policy of establishing a matching-fund financed rural health insurance system presents an exciting opportunity to improve people's access to health care.


title: Is evolutionary biology strategic science?

text: There is a profound need for the scientific community to be better aware of the policy context in which it operates. To address this need, Evolution has established a new Outlook feature section to include papers that explore the interface between society and evolutionary biology. This first paper in the series considers the strategic relevance of evolutionary biology. Support for scientific research in general is based on governmental or institutional expenditure that is an investment, and such investment is based on strategies designed to achieve particular outcomes, such as advance in particular areas of basic science or application. The scientific community can engage in the development of scientific strategies on a variety of levels, including workshops to explicitly develop research priorities and targeted funding initiatives to help define emerging scientific areas. Better understanding and communication of the scientific achievements of evolutionary biology, emphasizing immediate and potential societal relevance, are effective counters to challenges presented by the creationist agenda. Future papers in the Outlook feature section should assist the evolutionary biology community in achieving a better collective understanding of the societal relevance of their field.


title: Animal coronavirus vaccines: lessons for SARS.

text: Severe acute respiratory syndrome (SARS) emerged in China and spread globally as a human pandemic. It is caused by a new coronavirus (CoV) of suspect animal origin. The emergence of SARS stunned medical scientists, but veterinary virologists had previously recognized CoVs as causing fatal respiratory or enteric disease in animals with interspecies transmission and wildlife reservoirs. Because of its public health impact, major efforts are focused on development of SARS vaccines. Occurrence of CoV disease at mucosal surfaces necessitates the stimulation of local immunity, having an impact on the vaccine type, delivery and adjuvant needed to achieve mucosal immunity. Such immunity is often short-lived, requires frequent boosting and may not prevent re-infection, all factors complicating CoV vaccine design. SARS vaccine efforts should be enhanced by understanding the correlates of protection and reasons for the success or failure of animal CoV vaccines. This review will focus on studies of immunity and protection in swine to the enteric CoV, transmissible gastroenteritis (TGEV) versus the respiratory variant, porcine respiratory CoV (PRCV), comparing live, inactivated and subunit vaccines, various vaccine vectors, routes and adjuvants. In addition avian infectious bronchitis CoV (IBV) vaccines targeted for protection of the upper respiratory tract of chickens are discussed. Unfortunately, despite long-term efforts, effective vaccines to prevent enteric CoV infections remain elusive, and generally live, but not killed vaccines, have induced the most consistent protection against animal CoVs. Confirmation of the pathogenesis of SARS in humans or animals models that mimic SARS may further aid in vaccine design and evaluation.


title: Flooded Lung Generates a Suitable Acoustic Pathway for Transthoracic Application of High Intensity Focused Ultrasound in Liver.

text: Background: In recent years, high intensity focused ultrasound (HIFU) has gained increasing clinical interest as a non-invasive method for local therapy of liver malignancies. HIFU treatment of tumours and metastases in the liver dome is limited due to the adjacent ultrasound blocking lung. One-lung flooding (OLF) enables complete sonography of lung and adjoining organs including liver. HIFU liver ablation passing through the flooded lung could enable a direct intercostal beam path and thus improve dose deposition in liver. In this study, we evaluate the feasibility of an ultrasound guided transthoracic, transpulmonary HIFU ablation of liver using OLF. Methods: After right-side lung flooding, ultrasound guided HIFU was applied transthoracic- transpulmonary into liver to create thermal lesions in three pigs. The HIFU beam was targeted five times into liver, two times at the liver surface and three times deeper into the tissue. During autopsy examinations of lung, diaphragm and liver located in the HIFU path were performed. The focal liver lesions and lung tissue out of the beam path were examined histologically. Results: Fifteen thermal liver lesions were generated by transpulmonary HIFU sonication in all targeted regions. The lesions appeared well-demarcated in grey color with a cigar-shaped configuration. The mean length and width of the superficial and deeper lesions were 15.8 mm (range: 13-18 mm) and 5.8 mm (range: 5-7 mm), and 10.9 mm (range: 9-13 mm) and 3.3 mm (range: 2-5 mm), respectively. Histopathological, all liver lesions revealed a homogeneous thermal necrosis lacking vitality. There were no signs of damage of the overlying diaphragm and lung tissue. Conclusions: Flooded lung is a suitable pathway for applying HIFU to the liver, thus enabling a transthoracic, transpulmonary approach. The enlarged acoustic window could enhance the ablation speed for targets in the hepatic dome.


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title: The spike protein of transmissible gastroenteritis coronavirus controls the tropism of pseudorecombinant virions engineered using synthetic minigenomes.

text: The minimum sequence required for the replication and packaging of transmissible gastroenteritis virus (TGEV)-derived minigenomes has been determined. To this end, cDNAs encoding defective RNAs have been cloned and used to express heterologous spike proteins, to determine the influence of the peplomer protein in the control of TGEV tropism. A TGEV defective interfering RNA of 9.7 kb (DI-C) was isolated, and a cDNA complementary to DI-C RNA was cloned under the control of T7 promoter. In vitro transcribed DI-C RNA was replicated in trans upon transfection of helper virus-infected cells. A collection of DI-C deletion mutants (TGEV minigenomes) was generated and tested for their ability to be replicated and packaged. The size of the smallest minigenome replicated in trans was 3.3 kb. The rescue system was used to express the spike protein of an enteric TGEV isolate (C11) using as helper virus a TGEV strain (C8) that replicates very little in the gut. A mixture of two pseudorecombinant viruses containing either the helper virus genome or the minigenome was obtained. These pseudorecombinants display in the surface the S proteins from the enteric and the attenuated virus, and showed 10(4)-fold increase in their gut replication levels as compared to the helper isolate (C8). In addition, the pseudorecombinant virus increased its enteric pathogenicity as compared to the C8 isolate.


title: Salmonellosis in a free-ranging population of javelinas (Pecari tajacu) in south central Arizona.

text: The javelina, or collared peccary (Pecari tajacu), is indigenous to Arizona, New Mexico, and Texas in the United States and ranges throughout Latin America. From June 2004 to April 2005, an estimated 105 javelinas died in a mortality event that occurred in Tucson, Arizona, and neighboring areas. Clinical signs observed in sick animals included emaciation, dehydration, lethargy, and diarrhea. In addition, some animals showed labored breathing and hind limb weakness. We necropsied 34 animals, and enteritis was the most frequent clinical sign, followed by colitis, pulmonary congestion, and pneumonia. The only consistent findings were isolations of Clostridium perfringens type A and multiple Salmonella serotypes. Although it is likely that these javelinas ultimately succumbed to salmonellosis, it is unclear whether other unidentified underlying factors were involved. This is the first reported case of widespread salmonellosis in free-ranging javelinas.


title: An agent-based and spatially explicit model of pathogen dissemination in the intensive care unit.

text: OBJECTIVE To develop and disseminate a spatially explicit model of contact transmission of pathogens in the intensive care unit. DESIGN A model simulating the spread of a pathogen transmitted by direct contact (such as methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus) was constructed. The modulation of pathogen dissemination attending changes in clinically relevant pathogen- and institution-specific factors was then systematically examined. SETTING AND PATIENTS The model was configured as a hypothetical 24-bed intensive care unit. The model can be parameterized with different pathogen transmissibilities, durations of caregiver and/or patient contamination, and caregiver allocation and flow patterns. INTERVENTIONS Pathogen- and institution-specific factors examined included pathogen transmissibility, duration of caregiver contamination, regional cohorting of contaminated or infected patients, delayed detection and isolation of newly contaminated patients, reduction of the number of caregiver visits, and alteration of caregiver allocation among patients. MEASUREMENTS AND MAIN RESULTS The model predicts the probability that a given fraction of the population will become contaminated or infected with the pathogen of interest under specified spatial, initial prevalence, and dynamic conditions. Per-encounter pathogen acquisition risk and the duration of caregiver pathogen carriage most strongly affect dissemination. Regional cohorting and rapid detection and isolation of contaminated patients each markedly diminish the likelihood of dissemination even absent other interventions. Strategies reducing "crossover" between caregiver domains diminish the likelihood of more widespread dissemination. CONCLUSIONS Spatially explicit discrete element models, such as the model presented, may prove useful for analyzing the transmission of pathogens within the intensive care unit.


title: [Clinical characteristics and mechanism of liver injury in patients with severe acute respiratory syndrome].

text: OBJECTIVES To summarize the clinical features of liver injury in patients with severe acute respiratory syndrome (SARS), providing information for further mechanism and clinical study. METHODS The clinical and some laboratory data of 154 patients suffered from SARS were collected and analyzed, who were admitted to the isolation wards of Beijing You-an Hospital from March 11 to June 3, 2003. The serum samples were taken from 46 patients to detect IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-alpha, endotoxin and hepatitis related viral inclusions. In addition, 11 patients were detected ultrasonically, and 3 patients were described pathological features. Other two groups including 15 healthy care workers and 22 patients with chronic hepatitis in the same period were selected and analyzed as controls. RESULTS When being admitted to hospital, serum ALT and (or) AST levels were elevated in 37.7% SARS patients. Some of them (43.1%) were mild, and most of them (56.9%) were moderate. Abnormal liver function mainly resulted from ALT elevation (70.7%), then both ALT and AST elevation (22.4%). The aminotransferases in 75.9% SARS patients normalized within two weeks, while they elevated in four patients during the hospitalization. There was a significant difference in ALT/AST elevation rates between severe and mild clinical type (chi2=19.28, P<0.05). Serum total bilirubin values elevated in 8.4% patients. Serum albumin and prealbumin levels decreased in 24.0% and 28.6% patients, respectively. Creatine kinase (CK) and (or) creatine kinase MB (CK-MB) levels elevated in 72.7% patients when they hospitalized. The six kinds of interleukins and TNF-alpha levels during the first week of hospitalization were higher than those in the fourth week and in control groups (t>or=1.67, P<0.05). The levels of some factors, such as IL-1beta, IL-6 and IL-10 in patients with elevated ALT, were higher than those in ALT normal patients (t>or=2.36, P<0.05). In the first week, only 15.2% patients had elevated serum endotoxin level. Ultrasonic examination and pathological observation showed no special features, compared with those in common acute hepatitis patients. CONCLUSIONS All the results suggest strongly that there may be a systemic inflammatory response syndrome (SIRS) in most SARS patients in early stage, and the liver damage is only its partial signs. It may be beneficial to suppress cytokines storm in SARS patients in early stage, which will stop the progression of SIRS and release hepatic damage and improve the prognosis of SARS patients.


title: Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses.

text: This cross-sectional emergency department study of 70 wheezing children and 59 control subjects (2 mo to 16 yr of age) examined the prevalence of respiratory viruses and their relationship to age, atopic status, and eosinophil markers. Nasal washes were cultured for respiratory viruses, assayed for respiratory syncytial virus (RSV) antigen, and tested for coronavirus and rhinovirus RNA using reverse transcription-PCR (RT-PCR). Also evaluated were eosinophil numbers and eosinophil cationic protein (ECP) in both nasal washes and serum, along with total IgE and specific IgE antibody in serum. Respiratory viruses were detected in 82% (18 of 22) of wheezing infants younger than 2 yr of age and in 83% (40 of 48) of older wheezing children. The predominant pathogens were RSV in infants (detected in 68% of wheezing subjects) and rhinovirus in older wheezing children (71%), and both were strongly associated with wheezing (p < 0.005). RSV was largely limited to wheezing children younger than 24 mo of age, but rhinovirus was detected by RT-PCR in 41% of all infants and in 35% of nonwheezing control subjects older than 2 yr of age. After 2 yr of age the strongest odds for wheezing were observed among those who had a positive RT-PCR test for rhinovirus together with a positive serum radioallergosorbent testing (RAST), nasal eosinophilia, or elevated nasal ECP (odds ratios = 17, 21, and 25, respectively). Results from this study demonstrate that a large majority of emergent wheezing illnesses during childhood (2 to 16 yr of age) can be linked to infection with rhinovirus, and that these wheezing attacks are most likely in those who have rhinovirus together with evidence of atopy or eosinophilic airway inflammation.


The global epidemiology of childhood pneumonia 20 years on.


Successful drainage for life-threatening colonic perforation by a young physician on a remote island.


title: Pycnogenol, a procyanidin-rich extract from French maritime pine, inhibits intracellular replication of HIV-1 as well as its binding to host cells.

text: A procyanidin-rich extract from French maritime pine, Pycnogenol(R) (PYC), is known as an antioxidant that exerts a variety of physiological activities and is widely used in human beings. We report here that PYC inhibits not only human immunodeficiency virus type-1 (HIV-1) binding to host cells, but also its replication after entry in susceptible cells in vitro. Prominent biochemical alterations induced by PYC were the elevated expression of an intracellular antioxidant protein, manganese superoxide dismutase (Mn-SOD), and the inhibition of phosphorylation of the ribosomal S6 protein. Interestingly, ectopic expression of Mn-SOD inhibited HIV-1 replication as well. Inhibition of HIV-1 replication associated with induced expression of Mn-SOD in cells treated with PYC suggests the potential of this natural antioxidant inducer as a new anti-HIV-1 agent.


Mechanisms of viral pathogenesis. Distinct forms of reoviruses and their roles during replication in cells and host.


title: Progress towards the construction of a transmissible gastroenteritis coronavirus self-replicating RNA using a two-layer expression system.

text: Three transmissible gastroenteritis coronavirus (TGEV) defective interfering RNAs of 21, 10.6 and 9.7 kb (DI-A, DI-B and DI-C, respectively) were isolated. Dilution experiments showed that the largest DI RNA, DI-A, is a self-replicating RNA (replicon), and thus codes for a functional RNA polymerase and all the necessary replication signals. In order to engineer a cDNA encoding the RNA replicon a strategy based on the cloning of DI-C cDNA, followed by the insertion of the sequences required to complete the DI-A sequence has been developed. A cDNA complementary to DI-C RNA was cloned under the control of the CMV promoter (pDI-C-CMV) and rescued with a helper virus. In the ORF 1a of polymerase gene pDI-C-CMV contained a 10 kb deletion and in ORF 1b a 1.1 kb deletion. The consensus sequence corresponding to the deleted regions was cloned, and the deletions in pDI-C-CMV were replaced to yield a complete cDNA clone of DI-A, pDI-A-21-CMV, containing a full-length TGEV polymerase, driven by a CMV promoter. Expression of a functional TGEV polymerase is being investigated.


title: [Mucoprolassectomy with circular stapler: early results with a new device].

text: AIMS Stapled transanal mucosectomy is widely used by a lot of surgeon and in RCT, when compared to other haemorrhoidectomy techniques, it didn't show a real primacy. We describe results obtained with a new device, the EEA™ 33-mm Hemorrhoid and Prolapse Stapler Set con DST Series™ (Covidien™), used on 65 patients. PATIENTS AND METHODS Sixty-five patients underwent a stapled transanal mucosectomy for grade III (n° 20), IV (n° 15) haemorrhois and rectal prolapse (n° 30). The operation were performed by two surgeons. Results. Resected tissue had a mean width of 4.2 cm (3.3-6.1 cm) and a mean weight of 11 g (8-21 g). Surgical time were 22 min (15-35 min). Bleeding of the suture line were observed in 5 cases (7.7%) and they required a mean of 2 haemostatic stitch (1-5) in adsorbable suture 2/0. Mucoprolapsectomy was considered excellent in 55 patients (84.7%), good in 8 patients (12.3%), bad in 2 patients (3%) by surgeons. There were no early and late complications like bleeding, abscesses, anastomotic dehiscence. We report two case of perianal haematoma that don't need any treatment and one case of anal stenosis treated with dilatation therapy. Post-operative pain, estimated with VAS, emphasized an excellent response to NSAIDs in first postoperative day, in 10 cases (15.4%) we prolonged analgesic therapy for 3 days, in one case (1.5%) for one week. After 6 month all patients were revaluated with physical examination and anoscopy. Only one patient (1.5%) had an asymptomatic recurrence of rectal prolapse. CONCLUSION We conclude that the new device makes easy and standardized surgery. The new device reduce a lot of difficult in patients with tight pelvis and a small distance between ischiatic tubers.


title: Development in lipid drugs.

text: Lipopeptide lipid moieties induce dendritic cell (DC) internalization and epitopes are recognized by MHC, the major histocompatibility complex. HIV-1 (human immunodeficiency virus type 1) lipopeptide vaccine candidate elicits immune responses, and sustains HIV control after highly active antiretroviral therapy (HAART). Mp- and Dp-MART (anti-melanoma lipopeptides) induce strong CTL (cytolytic T lymphocyte) response. New BGTC, BGDA, TGKC lipoplexes mediate gene delivery, e.g., into mouse pancreatic tumor nodules. Triterpene glycyrrhizic acid (GL) inhibits SARS-CoV (severe acute respiratory syndrome associated coronavirus) replication. Compared to CDV (cidofovir), CDV ether lipid esters have enhanced activity against vaccinia (VV) and cowpox (CV) viruses in vitro. Oral treatment of VV and CV infected mice with CDV ether lipid esters, as effective as i.p. CDV, may be useful against orthopoxvirus infections in humans.


Early termination of THRILL, a prospective study of mechanical thrombectomy in patients with acute ischemic stroke ineligible for i.v. thrombolysis.


title: COVID 19: Diabetes and Obesity API-ICP Recommendations.

text: Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.


title: Severe acute respiratory syndrome: an overview.

text: Severe acute respiratory syndrome (SARS) is a severe pulmonary infection that has been identified in multiple outbreaks around the world after emerging from mainland China in early 2003. The syndrome is caused by SARS-associated coronavirus, a novel human infection. SARS-associated coronavirus is spread by multiple mechanisms, including direct contact and large-droplet aerosolization, and may be spread by droplet nuclei as well. Clinical disease is characterized by fever, dry cough, interstitial infiltrates, and variable progression to respiratory failure. No treatment has clearly been shown to be effective. Aggressive infection control measures to prevent viral spread are key to outbreak management.


title: [Assessing frailty in care practices : quick reminders in the light of the Covid-19 pandemic].

text: The Covid-19 pandemic has brought the concept of frailty back to the centre of debate, particularly for its relevance as a determinant of health outcomes. Frailty is concept that has long been a used gerontology. Today, several theoretical models of frailty are proposed in the literature, with as many tools to operationalize it. This article provides a brief outline of the three main models of frailty and the corresponding measurement instruments. The choice of the model as well as the choice of the assessment tool are discussed in the light of the clinical objectives pursued by health professionals. More generally, this article highlights the value of assessing frailty in routine practice to determine health outcomes and adapt care to individual needs.


title: [Effect of 1-year specific immunotherapy with standardized house dust mite vaccine on mild to moderate allergic asthmatic patients].

text: OBJECTIVE To evaluate the clinical efficacy and safety of specific immunotherapy (SIT) with standardized house dust mite (HDM) vaccine on allergic asthmatic patients. METHODS The investigation was a multicentre, randomized, double-blind, placebo-controlled clinical study. 132 patients with mild to moderate asthma who were allergic to HDM, recruited from three hospitals of China (The First Affiliated Hospital of Guangzhou Medical College, Shenyang General Military Hospital, Suzhou Children's Hospital), were randomly allocated to the active group (n = 66) or the control group (n = 66) respectively. The active group received SIT with a standardized depot Dermatophagoides pteronyssinus (Der p) extract absorbed to aluminium hydroxide (Alutard SQ, ALK-Abelló, Denmark), while the control group received a placebo containing histamine dihydrochloride by subcutaneous injections for 1 year. Treatment of each group was started from the initial concentration. Updosing was performed with weekly injections from four 10-fold dose-increase vials (active group: 100, 1,000, 10,000, 100,000 SQ-U/ml, control group: 0.01, 0.1, 1.0, 10 microg/ml. 100,000 SQ-U/ml of Der p extract contains 9.8 microg/ml of the majoy allergen Der p1). The single-dose was injected weekly with 0.2, 0.4, 0.8 ml of each concentration in turn from the preceding 3 vials, totally for 9 weeks. Subsequently, the dose with 0.1, 0.2, 0.4, 0.6, 0.8 ml of the highest concentration was injected weekly from the 10th-14th week and a maintenance dose with 1 ml was reached at the 15th week. The dosing interval was then gradually increased to 2, 4, 6 weeks until the end of the first 26-weeks updosing phase (phase I, H(1)). Thereafter, the dosing continued at 6-week intervals for maintenance phase (phase II, H(2)) till the end of the complete treatment. The patient was observed for at least 30 minutes in the clinic after each injection. RESULTS A total of 132 subjects were randomized and 129 subjects (64 in the active group, 65 in the control group) completed the whole study. Dropouts included three females because of poor compliance, being afraid of the epidemic of Severe Acute Respiratory Syndrome (SARS) and emigration respectively. Both groups were comparable at baseline in all clinical and laboratory parameters. The mean daily symptom scores in 4-weekly began to diverge at the 29th-32nd week with the active group showing a significant lower scores (0.17 +/- 0.33) than the control group (0.39 +/- 0.74, Z = 2.031, P < 0.05) till the end of the study. Significant difference was found in average daily symptom scores between H(1) (0.29 +/- 0.39) and H(2) (0.19 +/- 0.27) in the active group (Z = 2.923, P < 0.01), while no significant difference was found between H(1) (0.45 +/- 0.62) and H(2) (0.40 +/- 0.68) in the placebo group (Z = 1.885, P > 0.05). There were significant differences in subjective judgement of the improvement about overall asthmatic symptoms, exacerbation severity and exacerbation frequency between the active group (96.9%, 95.3%, 95.4%) and the control group (80.0%, 75.4%, 83.1%) with the self-evaluation questionnaire (chi(2) = 13.246, 11.576, 16.204, all P < 0.01). The trend line of daily medication scores in weekly intervals showed a significant decline. The mean daily medication score of phase II (0.20 +/- 0.36) was significant lower than that of phase I (0.33 +/- 0.67, Z = 3.344, P < 0.01), whereas the control group did not show a significant difference between phase II (0.35 +/- 0.96) and phase I (0.32 +/- 0.95, Z = 0.744, P > 0.05). After 1-year treatment, no significant differences were found in morning and evening peak expiratory flow of predicted value (PEF%), forced expiratory volume in one second of predicted value (FEV(1)/FVC), forced vital capacity of predicted value (FVC%), forced expiratory volume in one second to forced vital capacity ratio (FEV(1)/FVC), provoking dose decreasing FEV(1) by 20% (PD(20)-FEV(1)) between the active group [(97 +/- 17)%, (98 +/- 18)%, (91 +/- 11)%, (98 +/- 9)%, (82 +/- 10)%, 2.35 (7.9) micromol] and the control group [(99 +/- 19)%, (100 +/- 19)%, (90 +/- 14)%, (99 +/- 13)%, (82 +/- 9)%, 1.80 (7.8) micromol] (t = 0.170 - 0.630, Z = 0.264, all P > 0.05). Skin index (SI) to Der p in the active group (1.2 +/- 0.5) was significantly lower than that of the control group (1.5 +/- 0.6) after treatment (t = 2.395, P < 0.05). There was no significant difference in the level of serum sIgE against Der p between groups, which was 76.80 (97.0) kU/L in active group and 66.50 (99.3) kU/L in the control group (Z = 0.232, P > 0.05). The frequency of systemic adverse reactions graded by guidelines based on the position paper of European Academy of Allergology and Clinical Immunology (EAACI), was 5.7% and 1.8% of the total injections in the active group and the control group, respectively. Although significant difference was found in adverse reactions between groups (chi(2) = 4.705, P < 0.05), all were mild or moderate. The majority occurred within 30 minute after injection and were controlled well with symptomatic therapy. No any severe systemic adverse reaction was shown in the study. CONCLUSION One year specific immunotherapy with standardized house dust mite (HDM) vaccine significantly improved symptoms and reduced medication use in mild to moderate allergic asthmatic patients. SIT also reduced skin prick test reactivity to Der p. Complying with the EAACI immunotherapy guidelines, SIT with standardized HDM vaccine was a safe treatment.


title: Severe acute respiratory syndrome: lessons and uncertainties.

text: The outbreak of severe acute respiratory syndrome (SARS) has produced scientific and epidemiological discoveries with unprecedented speed, and this information has been spread instantaneously to the global health community through the internet. Within a few weeks, the coronavirus associated with SARS (SARS-CoV) was identified and sequenced. The source of the outbreak and the exact modes of transmission are still subjects of research. Important lessons can be learned from the SARS outbreak about both the scientific and the public health approach to emerging pathogens.


title: Antibiotic prescribing for upper respiratory tract infections in the Asia-Pacific region: A brief review.

text: This review highlights the high prevalence of antibiotic use for upper respiratory tract infections (URTIs) in a larger part of the Asia-Pacific region. Since URTIs are one of the common reasons for primary care consultations in this region, inappropriate use of antibiotic in both quantity and drug choice has greatly influenced the development of antibiotic resistance. Notwithstanding the paucity of Asia-Pacific data on the above issues, the available information suggests urgent actions needed to be taken to promote judicious antibiotic use at the point-of-care through a multi-pronged approach targeting the patients/consumers (or parents), healthcare providers and health care systems.


title: Air pollution and respiratory viral infection.

text: Despite current regulations, which limit the levels of certain air pollutants, there are still a number of adverse health effects that result from exposure to these agents. Numerous epidemiological studies have noted an association between the levels of air pollution and hospital admissions for a variety of different health reasons, including a number of respiratory diseases, as well as increased morbidity and mortality associated with various respiratory conditions and diseases. Because of the large impact respiratory virus infections have on morbidity and even mortality, it is important to understand whether and how exposure to common air pollutants could exacerbate the susceptibility to and severity of respiratory virus infections. This review focuses on current epidemiological and experimental studies, which have examined the association between and effect of air pollutants and respiratory viral infections, as well as potential mechanisms associated with these effects. Examined in this review are U.S. Environmental Protection Agency (EPA) "criteria" pollutants nitrogen dioxide (NO(2)), ozone (O(3)), and particulate matter (PM), as well as indoor pollutants such as environmental tobacco smoke (ETS) and combustion products of biomass fuels. Although a number of studies indicate associations between exposure to air pollutants and increased risk for respiratory virus infections, potential mechanisms mediating these effects are largely unexplored. Therefore, additional studies, both epidemiologic and mechanistic, are necessary to increase our understanding of how exposure to air pollutants could affect respiratory virus infections, especially in populations already at risk of developing significant morbidity/mortality after infections with respiratory viruses.


title: Recent progress in adjuvant discovery for peptide-based subunit vaccines.

text: Peptide-based subunit vaccines are of great interest in modern immunotherapy as they are safe, easy to produce and well defined. However, peptide antigens produce a relatively weak immune response, and thus require the use of immunostimulants (adjuvants) for optimal efficacy. Developing a safe and effective adjuvant remains a challenge for peptide-based vaccine design. Recent advances in immunology have allowed researchers to have a better understanding of the immunological implication of related diseases, which facilitates more rational design of adjuvant systems. Understanding the molecular structure of the adjuvants allows the establishment of their structure-activity relationships which is useful for the development of next-generation adjuvants. This review summarizes the current state of adjuvants development in the field of synthetic peptide-based vaccines. The structural, chemical and biological properties of adjuvants associated with their immunomodulatory effects are discussed.


title: Fecal rotaviruses, adenoviruses, coronavirus-like particles, and small round viruses in a cohort of rural Costa Rican children.

text: Excretion patterns of fecal viruses were studied in a cohort of 51 rural Costa Rican children. The presence of rotavirus, adenovirus, coronavirus-like particles, and small round viruses was investigated by electron microscopy (EM) in 2,516 extracts of weekly fecal specimens. Rotavirus was in addition studied with ELISA. The incidence of diarrhea was 0.7 episodes per child-year. Rotavirus was the most common virus (0.53 infection/child-year), followed by adenovirus (0.46 infection/child-year), and coronavirus-like particles (0.24 infection/child-year). However, the pathogenicity of rotavirus and adenovirus was low: only 3 of 24 rotavirus infections and 2 of 21 adenovirus infections were associated with diarrheal illness (12.5% and 9.5%, respectively). Small round viruses were detected in 23 specimens, but could not be assigned to a particular group of viruses. Children who excreted coronavirus-like particles and small round viruses were asymptomatic. Typical Norwalk-like viruses, astrovirus or calicivirus were not encountered. Rural conditions, good hygiene and prolonged breast feeding may explain the reduced exposure and pathogenicity of viral enteropathogens in rural Costa Rica.


title: Can Telehealth Ontario respiratory call volume be used as a proxy for emergency department respiratory visit surveillance by public health?

text: OBJECTIVE There is a paucity of information regarding the usefulness of non-traditional data streams for real-time syndromic surveillance systems. The objective of this paper is to examine the temporal relation between Ontario's emergency department (ED) visits and telephone health line (Telehealth) call volume for respiratory illnesses to test the feasibility of using Ontario's Telehealth system for real-time surveillance. METHODS Retrospective time-series data from the National Ambulatory Care Reporting System (NACRS) and the Telehealth Ontario program from June 1, 2004, to March 31, 2006, were analyzed. The added value of Telehealth Ontario data was determined by comparing it temporally with NACRS data, which uses the International Classification of Diseases (ICD) 10-Canadian Enhancement coding system for discharge diagnoses. RESULTS Telehealth Ontario had 216,105 calls for respiratory complaints, while 819,832 ICD-coded complaints from NACRS were identified with a comparable diagnosis of respiratory illness. Telehealth Ontario call volume was heavily weighted for the 0-4 years age group (49%), while the NACRS visits were mainly from those 18-64 years old (44%). The Spearman rank correlation coefficient was calculated to be 0.97, with the time-series analysis also resulting in significant correlations at lags (semi-monthly) 0 and 1, indicating that increases in Telehealth Ontario call volume correlate with increases in NACRS discharge diagnosis data for respiratory illnesses. CONCLUSION Telehealth Ontario call volume fluctuation reflects directly on ED respiratory visit data on a provincial basis. These call complaints are a timely, useful and representative data stream that shows promise for integration into a real-time syndromic surveillance system.


title: A novel protein polymorphism differentiates the California serotype of infectious bronchitis from other serotypes common to California.

text: The California (Cal) serotype of infectious bronchitis virus (IBV) was isolated from layer flocks in southern California in the early 1980s. Since then, it has spread to the broiler-producing regions of central California, where it has been implicated in respiratory disease outbreaks in vaccinated flocks. Lack of a procedure for quickly identifying IBV serotypes in commercial chicken flocks has prevented the causal association of the IBV Cal serotype with respiratory disease outbreaks. A protein polymorphism has been identified in the matrix protein of the Cal serotype; it appears to be unique among other common serotypes of infectious bronchitis virus found in California. This polymorphism can be identified on western blots using raw or concentrated infectious allantoic fluid as the source material. Identification of the Cal serotype and of serotypes in the Mass and Conn groups can be performed rapidly using field samples from suspect flocks. The identification of this polymorphism provides an alternative method for the rapid identification of the Cal serotype of IBV.


title: Impact of a Nationwide Training Program in Minimally Invasive Distal Pancreatectomy (LAELAPS).

text: OBJECTIVE To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). SUMMARY OF BACKGROUND DATA Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. METHODS From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005-2013) were compared with outcomes after training (2014-2015). RESULTS In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7-12] vs 7 [5-8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). CONCLUSION A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.


title: Generic detection of coronaviruses and differentiation at the prototype strain level by reverse transcription-PCR and nonfluorescent low-density microarray.

text: A nonfluorescent low-cost, low-density oligonucleotide array was designed for detecting the whole coronavirus genus after reverse transcription (RT)-PCR. The limit of detection was 15.7 copies/reaction. The clinical detection limit in patients with severe acute respiratory syndrome was 100 copies/sample. In 39 children suffering from coronavirus 229E, NL63, OC43, or HKU1, the sensitivity was equal to that of individual real-time RT-PCRs.


The fourth pillar of the Framework Convention on Tobacco Control: harm reduction and the international human right to health.


title: The amphotropic murine leukemia virus receptor gene encodes a 71-kilodalton protein that is induced by phosphate depletion.

text: The amphotropic murine leukemia virus (MuLV) can infect cells from a number of mammals, including humans, via its specific receptor. Basic knowledge of amphotropic MuLV receptor expression is likely to be useful in the development and improvement of gene therapy protocols based on amphotropic-pseudotyped vectors. To investigate the expression of the human receptor for the amphotropic MuLV (GLVR-2, newly termed Pit2), we determined its mRNA levels in several cell lines and found them to vary significantly. Induction of increased levels of mRNA after removal of phosphate from the media was observed in two osteosarcoma cell lines. The increase in GLVR-2 mRNA resulted in a concomitant rise in the levels of a 71-kDa protein specifically recognized by affinity-purified antibodies against GLVR-2. Using these antibodies, we were able to confirm the intracellular topology of the large hydrophilic domain between the proposed sixth and seventh transmembrane domains of the GLVR-2 protein. This assignment is in agreement with the fourth extracellular loop being outside the cell, consistent with the proposal that the fourth extracellular loop of GLVR-2 contains the envelope binding site.


Room to improve in government commitment to animal protection.


News and events.


title: Conservation of substrate specificities among coronavirus main proteases.

text: The key enzyme in coronavirus replicase polyprotein processing is the coronavirus main protease, 3CL(pro). The substrate specificities of five coronavirus main proteases, including the prototypic enzymes from the coronavirus groups I, II and III, were characterized. Recombinant main proteases of human coronavirus (HCoV), transmissible gastroenteritis virus (TGEV), feline infectious peritonitis virus, avian infectious bronchitis virus and mouse hepatitis virus (MHV) were tested in peptide-based trans-cleavage assays. The determination of relative rate constants for a set of corresponding HCoV, TGEV and MHV 3CL(pro) cleavage sites revealed a conserved ranking of these sites. Furthermore, a synthetic peptide representing the N-terminal HCoV 3CL(pro) cleavage site was shown to be effectively hydrolysed by noncognate main proteases. The data show that the differential cleavage kinetics of sites within pp1a/pp1ab are a conserved feature of coronavirus main proteases and lead us to predict similar processing kinetics for the replicase polyproteins of all coronaviruses.


The Struggle Against Pandemic Influenza A (H1N1) 2009.


title: Interference with virus and bacteria replication by the tissue specific expression of antibodies and interfering molecules.

text: Historically, protection against virus infections has relied on the use of vaccines, but the induction of an immune response requires several days and in certain situations, like in newborn animals that may be infected at birth and die in a few days, there is not sufficient time to elicit a protective immune response. Immediate protection in new born could be provided either by vectors that express virus-interfering molecules in a tissue specific form, or by the production of animals expressing resistance to virus replication. The mucosal surface is the largest body surface susceptible to virus infection that can serve for virus entry. Then, it is of high interest to develop strategies to prevent infections of these areas. Virus growth can be interfered intracellularly, extracellularly or both. The antibodies neutralize virus intra- and extracellularly and their molecular biology is well known. In addition, antibodies efficiently neutralize viruses in the mucosal areas. The autonomy of antibody molecules in virus neutralization makes them functional in cells different from those that produce the antibodies and in the extracellular medium. These properties have identified antibodies as very useful molecules to be expressed by vectors or in transgenic animals to provide resistance to virus infection. A similar role could be played by antimicrobial peptides in the case of bacteria. Intracellular interference with virus growth (intracellular immunity) can be mediated by molecules of very different nature: (i) full length or single chain antibodies; (ii) mutant viral proteins that strongly interfere with the replication of the wild type virus (dominant-negative mutants); (iii) antisense RNA and ribozyme sequences; and (iv) the product of antiviral genes such as the Mx proteins. All these molecules inhibiting virus replication may be used to obtain transgenic animals with resistance to viral infection built in their genomes. We have developed two strategies to target into mucosal areas either antibodies to provide immediate protection, or antigens to elicit immune responses in the enteric or respiratory surfaces in order to prevent virus infection. One strategy is based on the development of expression vectors using coronavirus derived defective RNA minigenomes, and the other relies on the development of transgenic animals providing virus neutralizing antibodies in the milk during lactation. Two types of expression vectors are being engineered based on transmissible gastroenteritis coronavirus (TGEV) defective minigenomes. The first one is a helper virus dependent expression system and the second is based on self-replicating RNAs including the information required to encode the TGEV replicase. The minigenomes expressing the heterologous gene have been improved by using a two-step amplification system based on cytomegalovirus (CMV) and viral promoters. Expression levels around 5 micrograms per 10(6) cells were obtained. The engineered minigenomes will be useful to understand the mechanism of coronavirus replication and for the tissue specific expression of antigen, antibody or virus interfering molecules. To protect from viral infections of the enteric tract, transgenic animals secreting virus neutralizing recombinant antibodies in the milk during lactation have been developed. Neutralizing antibodies with isotypes IgG1 or IgA were produced in the milk with titers of 10(6) in RIA that reduced virus infectivity by one million-fold. The recombinant antibodies recognized a conserved epitope apparently essential for virus replication. Antibody expression levels were transgene transgene copy number independent and were related to the transgene integration site. This strategy may be of general use since it could be applied to protect newborn animals against infections of the enteric tract by viruses or bacteria for which a protective MAb has been identified. Alternatively, the same strategy could be used to target the expression of antibio


title: Avian infectious bronchitis virus: a possible cause of reduced fertility in the rooster.

text: The formation of epididymal stones in the rooster epididymis is a widespread problem that has detrimental effects on sperm production and fertility. The cause of epididymal stones is unknown, but an infectious agent, the avian infectious bronchitis virus (AIBV), has been implicated. The goal of this study was to determine if administering the live attenuated AIBV vaccine to male chicks increases the incidence of stones in the epididymal region of the adult rooster. Specific pathogen free (SPF) Leghorn roosters were divided into two groups: a vaccine-free group (n = 7) and a group vaccinated with AIBV (n = 12). The vaccine was administered orally at 2, 4, 10, and 14 wk of age. Blood was drawn weekly to monitor antibodies to AIBV. At 26 wk of age, blood was obtained to determine testosterone concentrations, and reproductive tracts were removed to analyze daily sperm production and to detect epididymal stones. Nine of 12 vaccinated roosters developed stones, whereas those not given the vaccine did not develop stones. Serum testosterone concentrations were significantly (P < 0.05) reduced in vaccinated roosters with epididymal stones (3.6 +/- 0.30 ng/ml) when compared with nonvaccinated roosters that did not have epididymal stones (7.0 +/- 1.63 ng/ml). Testis weight was significantly (P < 0.05) reduced in vaccinated roosters with epididymal stones (12.1 +/- 0.76 g), as compared with nonvaccinated roosters without epididymal stones (15.2 +/- 0.81 g). Daily sperm production was significantly (P < 0.05) decreased in vaccinated roosters with epididymal stones (5.03 +/- 0.31 x 10(8) sperm/testis/day) when compared with nonvaccinated roosters without epididymal stones (7.43 +/- 0.52 x 10(8) sperm/testis/day). Comparing daily sperm production on a per gram basis, vaccinated roosters with epididymal stones had 4.38 +/- 0.14 x 10(7) sperm/g of testis, which was significantly (P < 0.05) smaller than nonvaccinated roosters without epididymal stones, which had 5.17 +/- 0.17 x 10(7) sperm/g of testis. We conclude that the use of a live attenuated AIBV vaccine increases the incidence of epididymal stones in roosters, resulting in decreased sperm production and decreased serum testosterone concentrations.


title: [Management of neurourological patients during the COVID-19 pandemic.]

text: OBJECTIVES To report the recommendations of an expert panel to reorganize Neurourology units and to prioritize examinations and both conservative and surgical treatments during the COVID-19 pandemic. MATERIALS AND METHODS: Non-systematic review of the literature and national experts' opinion summarizing the recommendations in the diagnosis, management, and follow-up of neurourological patients during the COVID-19 pandemic. A modified nominal group technique was used due to extraordinary meeting and mobility restrictions during COVID-19 pandemic. RESULTS: Neurourological patients have special physiological and pathological characteristics that make them more vulnerable to SARS-CoV-2 infection. For prioritization purposes, they encompass in Functional Urology patients and their management is considered non-urgentor delayable with no specific deadline of recovery from normality. However, it is important to identify individual situations jeopardising the upper urinary tract, urinary retention or predisposing to urinary infections/sepsis. A classification is provided prioritizing conservative/outpatient management and the surgical treatment of the events occurring in neurourological patients during the COVID-19 pandemic. CONCLUSIONS: In neurourological patients we can find exceptional clinical situations in which a delayed treatment could develop irreversible changes in the upper urinary tract, advocating a more urgent treatment inspecific scenarios.


title: Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat.

text: Human epidemiological studies have shown that low birth weight is associated with hypertension in adulthood. Rodent models of intrauterine growth retardation (IUGR) support these findings because offspring from undernourished dams develop hypertension. Angiotensin-converting enzyme 2 (ACE2) is a newly described renin-angiotensin system (RAS) component that competes with ACE for angiotensin peptide hydrolysis and therefore may modulate blood pressure. However, ACE2 potential participation in hypertension programming remains unknown, although RAS alterations were reported in IUGR models. Hence, we first investigated the tissue distribution of ACE2 and ACE in the rat and then whether hypertension programming differentially affects both enzymes. Using multiplex RT-PCR and in situ hybridization, we show that ACE2 mRNA is widely expressed and coregionalized with ACE. Moreover, tissues involved in blood pressure homeostasis (lung, heart, and kidney) express high levels of both enzymes. Enzymatic assays reveal that ACE2 and ACE are coactive in these tissues. Adult (4-month-old) offspring from 70% food-restricted dams throughout gestation (FR30 rats) present mild hypertension, impaired renal morphology, as well as elevated plasma angiotensin II and aldosterone, suggesting alterations of the systemic RAS. In FR30 rats, we show that ACE2 and ACE activities are increased only in the lung, whereas their mRNA expression is not significantly altered, showing that the enzymes display tissue-specific sensitivity to programming. Our results indicate that ACE2 and ACE are coexpressed in numerous rat tissues and that their increased activity in the lung of FR30 rats may participate in hypertension programming.


Antibody-dependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS.


title: Expression and characterization of a recombinant murine coronavirus 3C-like proteinase.

text: The replication of coronaviruses involves proteolytic processing of the gene 1 translation products, pp1a and pp1ab. One of the key enzymes in this process is predicted to be a virus-encoded 3C-like proteinase. In this report, we describe a bacterial system that has allowed us to express and characterize a recombinant murine coronavirus (MHV-JHM) 3C-like proteinase. The partially purified protein has been shown to exhibit proteolytic activity in trans and mutation analysis has been used to demonstrate the indispensability of Cys-3495 for enzymatic activity. Finally, the effect of class-specific proteinase inhibitors on the trans cleavage activity of the MHV 3C-like proteinase has been used to demonstrate the functional and structural homology of this enzyme to the picornavirus 3C proteinases.


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title: [Inflammatory bowel disease].

text: Inflammatory bowel disease (IBD) is heterogenous group of inflammatory disorders characterized by chronic immune activation and inflammation of the gastrointestinal tract, associated with numerous extraintestinal manifestations. Two most important forms are Crohn's disease and ulcerative colitis with several phenotypes. Etiopathogenesis of IBD is still unknown. Diagnostic and therapeutic approach of IBD is very complex and requires excellent knowledge of the clinical course and complications of the disease itself and therapy. The paper provides present therapeutic strategy with emphasis on the importance of mucosal healing and analysis of present knowledge of the role of biologics in the therapy of IBD.


Infection of hemagglutinating encephalomyelitis virus (HEV) at the visual pathways of rats.


Finding the cause of Kawasaki disease: a pediatric infectious diseases research priority.


Public health, preparedness and the World Health Organization response to swine flu in 2009.


May.


title: Viral respiratory disease in pregnancy.

text: PURPOSE OF REVIEW Recently there has been an increased concern over viral respiratory infections and their potential for a pandemic. This concern makes it important to review the most current guidelines for the management of viral respiratory diseases in pregnancy. RECENT FINDINGS The topics covered are influenza, avian influenza, and severe acute respiratory syndrome. SUMMARY Pregnant women have an increased susceptibility to viral respiratory diseases. The most common respiratory virus to infect pregnant women is influenza. All women who intend to become pregnant or are pregnant should receive the influenza vaccine. If a pregnant woman develops influenza she should be treated with supportive care. Antiviral medications should be reserved for cases where the benefits outweigh the risks. Avian influenza (H5N1) is a new emerging virus usually contracted from direct contact with diseased birds. There is no commercially available vaccine at this time to prevent infection. Pregnant women should be treated aggressively with supportive care and antiviral medications, as the significant risk of maternal mortality outweighs the potential fetal risks. Pregnant women diagnosed clinically with severe acute respiratory syndrome should be treated empirically, as a serologic diagnosis can take weeks to confirm. The treatment of pregnant women with severe acute respiratory syndrome should be without ribavirin.


title: HLA predictions from the bronchoalveolar lavage fluid samples of five patients at the early stage of the wuhan seafood market COVID-19 outbreak.

text: We are in the midst of a global viral pandemic, one with no cure and a high mortality rate. The Human Leukocyte Antigen (HLA) gene complex plays a critical role in host immunity. We predicted HLA class I and II alleles from the transcriptome sequencing data prepared from the bronchoalveolar lavage fluid samples of five patients at the early stage of the COVID-19 outbreak. We identified the HLA-I allele A*24:02 in four out of five patients, which is higher than the expected frequency (17.2%) in the South Han Chinese population. The difference is statistically significant with a p-value less than 10-4. Our analysis results may help provide future insights on disease susceptibility.


title: A mouse model of swine influenza virus H9N2 infection with acute lung injury.

text: UNLABELLED BALB/c mice inoculated intranasally with A/swine/HeBei/012/2008/ (H9N2) virus (SIV), showing acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), were observed for morbidity (lung histopathology, lung coefficient, lung wet/dry weight (W/D) ratio, arterial blood gas characteristics and inflammatory cells in bronchial alveolar lavage fluid (BALF)) and mortality. The results showed that, (1) on days 1-4 post infection (p.i.), mice appeared depressed and showed ruffled fur, reduced food intake, weight loss and hypoxemia with a decreased arterial partial oxygen pressure and an increased partial carbon dioxide pressure. (2) From day 4 p.i., mice began to die and showed pulmonary edema, hemorrhage and inflammatory cells in the alveolar exudate. The lung coefficient and lung W/D ratio significantly increased. (3) On days 3-8 p.i., inflammatory cells, especially alveolar macrophages and polymorphonuclears (PMNs) in BALF significantly increased. (4) The mortality rate reached 62.5%. This study established a successful animal model of ALI induced by infection with H9N2 SIV which may help in further investigations of the pathogenesis of human ALI/ARDS induced by H9N2 SIV infection. KEYWORDS wine influenza virus; H9N2 subtype; acute lung injury; mouse.


Editorial: Fifty years of health services in Tanzania: What next?


title: Using Telemedicine During the COVID-19 Pandemic.

text: Telemedicine is the delivery of health care services using information or communication technology. In the current pandemic scenario, telemedicine can supplement health-care delivery in the absence of in-person visit. The Government of India has recently launched the e-sanjeevani OPD, a National teleconsultation service, which has been adopted by many state governments as mandatory for health-care providers. With Indian Medical Association issuing an advisory against the use of telemedicine except in few situations, a lot of confusion exists in the mind of a pediatrician. Despite the uncertain situation, we have to remember that other diseases shall not stall in the face of a pandemic. Since telemedicine is an evolving subject, training of medical professionals, clear guidelines and good quality internet service systems will go a long way in increasing the acceptability of telemedicine in the Indian population. We herein discuss issues related to using telemedicine during the SARS-CoV-2 pandemic.


Haemophilus influenzae associated with acute respiratory illnesses in young children.


title: Expression of cellular oncogene Bcl-xL prevents coronavirus-induced cell death and converts acute infection to persistent infection in progenitor rat oligodendrocytes.

text: Murine coronavirus mouse hepatitis virus (MHV) causes persistent infection of the central nervous system (CNS) in rodents, which has been associated with demyelination. However, the precise mechanism of MHV persistence in the CNS remains elusive. Here we show that the progenitor oligodendrocytes (central glial 4 [CG-4] cells) derived from newborn rat brain were permissive to MHV infection, which resulted in cell death, although viral replication was restricted. Interestingly, treatment with fetal bovine serum or exogenous expression of cellular oncogene Bcl-xL prevented CG-4 cells from MHV-induced cell death. Significantly, overexpression of Bcl-xL alone was sufficient to convert acute to persistent, nonproductive infection in CG-4 cells. This finding indicates that intracellular factors rather than viral components play a critical role in establishing viral persistence in CNS cells. Although viral genomic RNAs continuously persisted in Bcl-xL-expressing CG-4 cells over 10 passages, infectious virus could no longer be isolated beyond 2 passages of the cell. Such a phenomenon resembles the persistent MHV infection in animal CNS. Thus, the establishment of a persistent, nonproductive infection in CG-4 cells may provide a useful in vitro model for studying viral persistence in animal CNS. The data also suggest that direct virus-host cell interaction is one of the underlying mechanisms that regulate viral persistence in CNS cells.


title: Severe acute respiratory syndrome (SARS) and the rhetorical construction of "bad" scientific work.

text: How are secondary accounts of "bad" scientific practice constructed? How do they engage with the primary data produced by "bad" scientists? And what happens to those primary data as generations of secondary accounts purporting to describe them accumulate? This paper addresses such questions via a case study of Dr. Hong, a microbiologist accused of "bad" scientific practice by numerous secondary accounts of the 2003 SARS outbreak. Bringing Hong's own account of his own actions into dialogue with one of the most influential secondary accounts of his actions, the paper highlights the gross disparity between the two. Having argued that the rhetorical structuring of the secondary account is, ultimately, responsible for Hong's characterisation as a "bad" scientist, it then moves to explore how subsequent accounts developed their own characterisations. What becomes clear is that as secondary accounts began feeding off one another, references to Hong's account disappeared. Aided by the concepts of the "vanishing" and the "phantasm", the paper concludes with a consideration of how this process left Hong's work with a very peculiar form of existence.