title: DIAGNOSTIC IMPACT OF BEDSIDE CHEST X-RAY FEATURES OF 2019 NOVEL CORONAVIRUS IN THE ROUTINE ADMISSION AT THE EMERGENCY DEPARTMENT: CASE SERIES FROM LOMBARDY REGION

text: PURPOSE: To evaluate the diagnostic accuracy and the imaging features of routine admission chest X-ray in patients suspected for novel Coronavirus 2019 (SARS-CoV-2) infection. METHOD: We retrospectively evaluated clinical and X-ray features in all patients referred to the emergency department for suspected SARS-CoV-2 infection between March 1(st) and March 13(th). A single radiologist with more than 15 years of experience in chest-imaging evaluated the presence and extent of alveolar opacities, reticulations, and/or pleural effusion. The percentage of lung involvement (range <25% to 75-100%) was also calculated. We stratified patients in groups according to the time interval between symptoms onset and X-ray imaging (≤ 5 and > 5 days) and according to age (≤ 50 and > 50 years old). RESULTS: A total of 518 patients were enrolled. Overall 314 patients had negative and 204 had positive RT-PCR results. Lung lesions in patients with SARS-Cov2 pneumonia primarily manifested as alveolar and interstitial opacities and were mainly bilateral (60.8%). Lung abnormalities were more frequent and more severe by symptom duration and by increasing age. The sensitivity and specificity of chest X-ray at admission in the overall cohort were 57% (95% CI = 47-67) and 89% (83-94), respectively. Sensitivity was higher for patients with symptom onset > 5 days compared to ≤ 5 days (76% [62-87] vs 37% [24-52]) and in patients > 50 years old compared to ≤ 50 years (59% [48-69] vs 47% [23-72]), at the expense of a slightly lower specificity (68% [45-86] and 82% [73-89], respectively). CONCLUSIONS: Overall chest X-ray sensitivity for SARS-CoV-2 pneumonia was 57%. Sensitivity was higher when symptoms had started more than 5 days before, at the expense of lesser specificity, while slightly higher in older patients in comparison to younger ones.


title: HIGHLIGHTS FROM THE 2016 NORTH AMERICAN CYSTIC FIBROSIS CONFERENCE

text: The 30th annual North American Cystic Fibrosis Conference (NACFC) was held in Orlando, FL, on Oct. 27-29, 2016. Abstracts were published in a supplement to Pediatric Pulmonology.(1) This review summarizes several major topic areas addressed at the conference: the pathophysiology of cystic fibrosis (CF) lung disease,clinical trials, clinical management issues, and quality improvement. We sought to provide an overview of emerging concepts in several areas of CF research and care, rather than a comprehensive review of the conference. Citations from the conference are by first author and abstract number or symposium number, as designated in the supplement.


docid: otoqejtg

title: Synergistic antiviral effect of Galanthus nivalis agglutinin and nelfinavir against feline coronavirus

text: Abstract Feline infectious peritonitis (FIP) is a fatal disease in domestic and nondomestic felids caused by feline coronavirus (FCoV). Currently, no effective vaccine is available for the prevention of this disease. In searching for agents that may prove clinically effective against FCoV infection, 16 compounds were screened for their antiviral activity against a local FCoV strain in Felis catus whole fetus-4 cells. The results showed that Galanthus nivalis agglutinin (GNA) and nelfinavir effectively inhibited FCoV replication. When the amount of virus preinoculated into the test cells was increased to mimic the high viral load present in the target cells of FIP cats, GNA and nelfinavir by themselves lost their inhibitory effect. However, when the two agents were added together to FCoV-infected cells, a synergistic antiviral effect defined by complete blockage of viral replication was observed. These results suggest that the combined use of GNA and nelfinavir has therapeutic potential in the prophylaxis and treatment of cats with early-diagnosed FIP.


Abstract 41. Herpes simplex virus infection of neuronal cells in vitro


title: Urologic Oncology Practice During COVID-19 Pandemic: A Systematic Review on What can be Deferrable vs. Nondeferrable

text: PURPOSE: To provide a review of high-risk urologic cancers and the feasibility of delaying surgery without impacting oncologic or mortality outcomes. MATERIALS AND METHODS: A thorough literature review was performed using PubMed and Google Scholar to identify articles pertaining to surgical delay and genitourinary oncology. We reviewed all relevant articles pertaining to kidney, upper tract urothelial cell (UTUC), bladder, prostate, penile, and testicular cancer in regard to diagnostic, surgical, or treatment delay. RESULTS: The majority of urologic cancers rely on surgery as primary treatment. Treatment of unfavorable intermediate or high-risk prostate cancer, can likely be delayed for 3-6 months without affecting oncologic outcomes. Muscle-invasive bladder cancer (MIBC) and testicular cancer can be treated initially with chemotherapy. Surgical management of T3 renal masses, high-grade upper tract urothelial carcinoma, and penile cancer should not be delayed. CONCLUSION: The majority of urologic oncologic surgeries can be safely deferred without impacting long-term cancer specific or overall survival. Notable exceptions are MIBC, high-grade UTUC, large renal masses, testicular and penile cancer. Joint decision making among providers and patients should be encouraged. Clinicians must manage emotional anxiety and stress when decisions around treatment delays are necessary as a result of a pandemic.


title: Effects of lockdown on human sleep and chronotype during the COVID-19 pandemic

text: COVID-19 lockdown induced severe changes in light exposure and social cues. Leone et al. show that sleep is later and longer on weekdays, with lower social jetlag during lockdown compared with a controlcondition, in the same subjects (n=1021). Sleep quality is not affected but chronotype is later, which might eventually lead to desynchronization.


title: Effects of epidermal growth factor on atrophic enteritis in piglets induced by experimental porcine epidemic diarrhoea virus

text: Abstract Epidermal growth factor (EGF) promotes gastrointestinal mucosal recovery by stimulating the mitogenic activity of intestinal crypt epithelial cells. The aim of this study was to determine the effects of EGF on atrophic enteritis induced in piglets by experimental infection with porcine epidemic diarrhoea virus (PEDV) strain Dr13. Two groups of 12 conventional, colostrum-deprived, 1-day-old, large White-Duroc cross breed piglets were inoculated orally with PEDV (3×105 50% tissue culture infective doses), with or without EGF (10μg/kg/day, intraperitoneally once daily for 4 days after infection) and compared to 12 uninfected, untreated control piglets. PEDV+EGF piglets had less severe clinical signs than PEDV only piglets at 48 and 60h post-infection (hpi). Histologically, the ratio of villous height:crypt depth of PEDV+EGF piglets was significantly higher than PEDV only piglets at 36 and 48hpi. Immunohistochemistry for Ki67 demonstrated increased proliferation in intestinal crypt epithelial cells of PEDV+EGF piglets compared to PEDV only piglets at 36, 48 and 60hpi. EGF stimulates proliferation of intestinal crypt epithelial cells and promotes recovery from atrophic enteritis in PEDV-infected piglets.


title: Pandemics, regional outbreaks, and sudden-onset disasters

text: Pandemics of influenza, cholera, and plague are part of global history. Regional epidemics and pandemics of infectious diseases, primarily influenza A, continue to cause significant morbidity and mortality while remaining unpredictable in nature. Sudden-onset disasters such as earthquakes and floods occur with little warning. The consequences of climate change and environmental degradation can only be expected to increase the incidence of some infectious diseases and weather-related crises, adding to the unpredictability of such events. Health system leaders, both in public health and healthcare, need to understand the international context and how coordination and response across or within jurisdictions will improve the likelihood of successful management of challenges. Public health emergencies respect no borders or political structures. The ability of institutions to adapt quickly can make a difference in health outcomes and a community’s trust in those institutions.


title: Portable pulsed xenon ultraviolet light disinfection in a teaching hospital animal laboratory in China

text: Abstract An animal laboratory in a teaching hospital is a possible cause of cross infection. We aimed to assess the infection control in our animal laboratory and evaluate the disinfectant effects of a portable pulsed xenon ultraviolet (PX-UV) machine. Samples were taken from the surface of research tables, other high touch places, such as doorknobs, weighing scales, and handles of trolleys, and from air in the barrier system pre- and post-manual cleaning and post-PX-UV disinfection. The bacteria types were identified. We found that routine manual cleaning significantly reduced bacterial colony form unit (CFU)/cm2 (P = .02), and the median of CFU/cm2 reduced from 0.5 pre-cleaning to zero post-cleaning. PX-UV disinfection also significantly reduced residual bacterial counts (P = .002), with the highest counts 10 pre-PX-UV disinfection and 1 afterwards. Without manual cleaning, PX-UV disinfected surfaces significantly (P < .001), median count 6 pre-PX-UV disinfection and zero afterwards. PX-UV significantly reduced bacterial colony counts in the air with the median count falling from 6 to zero (P < .001). Some of the 21 species of pathogens we identified in the current study are pathogenic, resistant to antibiotics, and able to cause nosocomial infections and zoonosis. PX-UV reduced counts of most of the pathogens. PX-UV is an effective agent against these pathogens.


Radioaerosols and the updated EANM guideline in ventilation/perfusion imaging


title: Viruses that multiply in the gut and cause endemic and epidemic gastroenteritis

text: Abstract Background: Acute infectious diarrhea in young children is a leading cause of morbidity and mortality in developing countries. Even in developed countries, infectious enteritis is second only to respiratory infections as a cause of morbidity in early childhood. Objective: To nominate the various viral agents that cause enteritis, discuss the pathogenesis, clinical features, epidemiology and diagnostic procedures employed. Study design: Pertinent literature was reviewed and the findings of investigations carried out on viral enteritis by various colleagues recalled. Results: The viruses causing gastroenteritis include: Rotaviruses; Adenoviruses-especially Ad 31, Ad 40 and Ad 41; members of the Caliciviridae, e.g. Norwalk virus, Hawaii virus, Snow Mountain virus, Taunton virus, Southampton virus, Toronto virus (formerly mini-reovirus) and others; Astrovirus; Coronavirus; Torovirus; Cytomegalovirus (CMV) and possibly Picobirnavirus. Enteritis-producing viruses replicate in columar epithelial cells in the distal parts of villi of the small intestine. Two mechanisms are addressed to explain why diarrhea occurs. Clinically, the main expression of illness is a watery diarrhea that lasts 24 h to about 7 days. Vomiting is of shorter duration and may not always accompany the diarrhea. Fever is generally ⩽ 38.5°C. Virus is shed in the stool for about 3–7 days. Diagnostic procedures employ electron microscopy (EM), immune electron microscopy (IEM), enzyme-linked immunosorbent assay (ELISA), time-resolved fluoroimmunoassay (TR-FIA), latex agglutination, polyacrylamide gel electrophoresis (PAGE) and the polymerase chain reaction (PCR). Conclusion: In developed countries viral enteritis among young children may be up to three times more common than bacterial gut disease. With the exception of CMV enteric involvement, the stool is characteristically not bloody and white blood cells are not found. Patient management may involve the employment of IV replacement therapy to counter dehydration and electrolyte imbalance. Milder cases may be managed with oral rehydration.


docid: abpromur

title: Learning important clinical skills during junior residency in Japan: A Case of Gram Stain


title: Acute asthma management during SARS-CoV2-pandemic 2020

text: Abstract Background The current COVID-19 pandemic has changed many medical practices in order to provide additional protection to both our patients and our healthcare providers. In many cases this includes seeing patients through electronic means such as telehealth or telephone rather than seeing them in person. Asthma exacerbations cannot always be treated in this way. Problem Current emergency unit asthma guidelines recommend bronchodilators be administered by metered dose inhaler (MDI) and spacer for mild-moderate asthma and include it as a choice even in severe asthma, but many emergency units continue to prefer nebulised therapy for patients who urgently require beta-agonists. The utilization of nebulised therapy potentially increases the risk of aerosolization of the coronavirus. Since nosocomial transmission of respiratory pathogens is a major threat in the context of the SARS-CoV-2 pandemic, use of nebulised therapy is of even greater concern due to the potential increased risk of infection spread to nearby patients and health-care workers. Practical implications We propose a risk stratification plan that aims to avoid nebulised therapy, when possible, by providing an algorithm to help better delineate those who require nebulised therapy. Protocols that include strategies to allow flexibility in using MDIs rather than nebulisers in all but the most severe patients should help mitigate this risk of aerosolised infection transmission to patients and health care providers. Furthermore, expedient treatment of patients with high dose MDI therapy augmented with more rapid initiation of systemic therapy may help ensure patients are less likely to deteriorate to the stage where nebulisers are required.


title: The coronavirus avian infectious bronchitis virus requires the cell nucleus and host transcriptional factors

text: Abstract Replication of avian infectious bronchitis virus in permissive BHK-21 cells is blocked when these cells are enucleated or irradiated with ultraviolet light prior to infection, or if cells are treated with α-amanitin during the virus growth cycle. This coronavirus, like influenza virus, can replicate normally in the presence of α-amanitin in Chinese hamster ovary cells which possess a drug-resistant RNA polymerase II. These findings indicate that avian infectious bronchitis virus requires the intact cell nucleus and one or more host transcriptional functions for productive infections. Preliminary data suggest that these cellular functions involve some aspect of virus-directed RNA synthesis.


title: CIRUGÍA DE LA PARED ABDOMINAL DESPUÉS DEL SARS-COV-2: ¿ES HORA DE RESTABLECER LOS PROCEDIMIENTOS NO ESENCIALES POSPUESTOS?

text: Resumen La pandemia por el COVID-19 nos ha encontrado desprotegidos ante la dificultad para dar una respuesta sanitaria adecuada y rápida. La red de hospitales del sistema sanitario público ha dispuesto la mayoría de los recursos para el tratamiento de los pacientes afectos por la infección. Las cirugías no esenciales (no prioritarias) han sido aplazadas. El reinicio optimo y proporcionado de estas cirugías no prioritarias puede representar un problema. En el presente artículo se ofrece una perspectiva técnica y no técnica del reinicio de las cirugías no prioritarias desde la óptica de la cirugía de la pared abdominal. Abstract Pandemic by the COVID-19 has found us unprotected to provide an adequate and rapid sanitary response. The hospital network of our public health system has provided most of the resources for the treatment of patients affected by the infection. Non-essential (non-priority) surgeries have been postponed. The optimal and proportionate reestablishment of these non-priority surgeries can be a problem. This article offers a technical and non-technical view of reestablishment non-priority surgeries from the perspective of abdominal wall surgery.


title: Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody

text: Abstract The presence of maternal antibodies protected suckling C57BL/6 mice from the clinical manifestations of the acute encephalomyelitis caused by mouse hepatitis virus, strain JHM (MHV-JHM), a coronavirus, even though histological evidence of encephalomyelitis was found at early times after inoculation. 100% of infected suckling mice developed a fatal disease in the absence of maternal antibody. By 14 days after inoculation, the brains of all antibody-protected mice examined were nearly normal on histological examination. At 3–8 weeks post-inoculation, approximately 40% of the antibody-protected mice developed a neurological disease characterized by hindlimb paralysis and wasting. Evidence of inflammation and demyelination was apparent in the spinal cord and brainstem. The mice that remained asymptomatic at this time showed few signs of inflammation and none developed clinical disease over the following 9 months. Viral antigen could be detected in most of the mice examined at all times after inoculation, whether symptomatic or not, and was particularly evident in the animals with hindlimb paralysis. MHV-JHM could be consistently cultured from the mice with hindlimb paralysis. These results show that maternal immune factors can completely protect susceptible mice from the acute, fatal, clinical encephalomyelitis caused by MHV-JHM, but cannot prevent the establishment of a latent state and subsequent development of virus-induced, clinically evident, demyelinating disease. This model will be useful for studying the virus and host factors important for the development of MHV-JHM latency and subsequent virus-induced demyelination.


title: Dynamically-Driven Enhancement of the Catalytic Machinery of the SARS 3C-Like Protease by the S284-T285-I286/A Mutations on the Extra Domain

text: Previously we revealed that the extra domain of SARS 3CLpro mediated the catalysis via different mechanisms. While the R298A mutation completely abolished the dimerization, thus resulting in the inactive catalytic machinery, N214A inactivated the enzyme by altering its dynamics without significantly perturbing its structure. Here we studied another mutant with S284-T285-I286 replaced by Ala (STI/A) with a 3.6-fold activity increase and slightly enhanced dimerization. We determined its crystal structure, which still adopts the dimeric structure almost identical to that of the wild-type (WT), except for slightly tighter packing between two extra-domains. We then conducted 100-ns molecular dynamics (MD) simulations for both STI/A and WT, the longest reported so far for 3CLpro. In the simulations, two STI/A extra domains become further tightly packed, leading to a significant volume reduction of the nano-channel formed by residues from both catalytic and extra domains. The enhanced packing appears to slightly increase the dynamic stability of the N-finger and the first helix residues, which subsequently triggers the redistribution of dynamics over residues directly contacting them. This ultimately enhances the dynamical stability of the residues constituting the catalytic dyad and substrate-binding pockets. Further correlation analysis reveals that a global network of the correlated motions exists in the protease, whose components include all residues identified so far to be critical for the dimerization and catalysis. Most strikingly, the N214A mutation globally decouples this network while the STI/A mutation alters the correlation pattern. Together with previous results, the present study establishes that besides the classic structural allostery, the dynamic allostery also operates in the SARS 3CLpro, which is surprisingly able to relay the perturbations on the extra domain onto the catalytic machinery to manifest opposite catalytic effects. Our results thus imply a promising avenue to design specific inhibitors for 3CL proteases by disrupting their dynamic correlation network.


title: Severe Middle East Respiratory Syndrome (MERS) Pneumonia

text: Abstract Middle East Respiratory Syndrome (MERS) is a viral respiratory infection, which ranges from asymptomatic infection to severe pneumonia and multiorgan failure, caused by a novel coronavirus named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Majority of cases have been reported from Saudi Arabia. MERS cases occur as sporadic cases or as clusters or hospital outbreaks. Dromedary camels are thought to be a host for MERS-CoV. Direct contact with dromedary camels within 14days prior to infection was identified as an independent risk factor for MERS. Diagnosis of MERS is based on a positive real-time reverse transcriptase polymerase chain reaction (rRT-PCR), obtained from a respiratory specimen. The mainstay of management of MERS-CoV infection is supportive care. There is no specific antiviral therapy for MERS-CoV infection at present, although several modalities of treatment options have been examined or are under investigation.


title: Bacterial coinfections in children with viral wheezing

text: Bacterial coinfections occur in respiratory viral infections, but the attack rates and the clinical profile are not clear. The aim of this study was to determine bacterial coinfections in children hospitalized for acute expiratory wheezing with defined viral etiology. A total of 220 children aged 3 months to 16 years were investigated. The viral etiology of wheezing was confirmed by viral culture, antigen detection, serologic investigation, and/or PCR. Specific antibodies to common respiratory bacteria were measured from acute and convalescent serum samples. All children were examined clinically for acute otitis media, and subgroups of children were examined radiologically for sinusitis and pneumonia. Rhinovirus (32%), respiratory syncytial virus (31%), and enteroviruses (31%) were the most common causative viruses. Serologic evidence of bacterial coinfection was found in 18% of the children. Streptococcus pneumoniae (8%) and Mycoplasma pneumoniae (5%) were the most common causative bacteria. Acute otitis media was diagnosed in 44% of the children. Chest radiographs showed alveolar infiltrates in 10%, and paranasal radiographs and clinical signs showed sinusitis in 17% of the older children studied. Leukocyte counts and serum C-reactive protein levels were low in a great majority of patients. Viral lower respiratory tract infection in children is often associated with bacterial-type upper respiratory tract infections. However, coexisting bacterial lower respiratory tract infections that induce systemic inflammatory response are seldom detected.


COVID-19 Pneumonia in Patients With HIV: A Case Series


title: A novel assay for detecting canine parvovirus using a quartz crystal microbalance biosensor

text: Abstract Rapid and accurate diagnosis is crucial to reduce both the shedding and clinical signs of canine parvovirus (CPV). The quartz crystal microbalance (QCM) is a new tool for measuring frequency changes associated with antigen–antibody interactions. In this study, the QCM biosensor and ProLinker™ B were used to rapidly diagnosis CPV infection. ProLinker™ B enables antibodies to be attached to a gold-coated quartz surface in a regular pattern and in the correct orientation for antigen binding. Receiver operating characteristics (ROC) curves were used to set a cut-off value using reference CPVs (two groups: one CPV-positive and one CPV-negative). The ROC curves overlapped and the point of intersection was used as the cut-off value. A QCM biosensor with a cut-off value of −205Hz showed 95.4% (104/109) sensitivity and 98.0% (149/152) specificity when used to test 261 field fecal samples compared to PCR. In conclusion, the QCM biosensor described herein is eminently suitable for the rapid diagnosis of CPV infection with high sensitivity and specificity. Therefore, it is a promising analytical tool that will be useful for clinical diagnosis, which requires rapid and reliable analyses.


title: SARS-COV-2 infection is likely to be androgen mediated

text: [Figure: see text]


title: Generation of a Broadly Useful Model for COVID-19 Pathogenesis Vaccination, and Treatment

text: Summary COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis, and to evaluate new therapies and vaccines.


title: The Impact of Severe Acute Respiratory Syndrome on Otorhinolaryngological Services at The Prince of Wales Hospital in Hong Kong

text: Objectives/Hypothesis The objective was to describe the impact of severe acute respiratory syndrome (SARS) on the services of the division of otorhinolaryngology—head and neck surgery at an academic tertiary referral hospital in Hong Kong. Study Design Descriptive. Methods Records of general and subspecialty outpatient attendance, ward admissions, ward bed occupancy, and elective and emergency surgery were obtained for the period since the SARS outbreak and for an equivalent period before the outbreak. The changes in these parameters were determined against the background of new SARS cases. Results Since the outbreak of SARS in March 2003, the weekly outpatient clinic attendance has declined by 59%, the number of operations performed by 79%, the average ward bed occupancy rate by 79% and the daily admission rate by 84%. A dramatic increase of 300% in the number of patients defaulting on their outpatient appointments was recorded. Conclusion The substantial decrease in otorhinolaryngological services at an academic tertiary referral hospital in Hong Kong has been multifaceted. The decrease in attendance at the outpatient clinics reflects the increased number of patients defaulting on their appointments. Nonessential elective surgery was suspended soon after the outbreak, accounting for the decrease in the number of surgical procedures performed and partially for the decrease in ward bed occupancy and ward admissions. The temporary closure of the accident and emergency department contributed to the decrease in ward admissions and emergency surgical procedures. The reduced service offered by the hospital is having an impact on the quality of care available to patients with non–life‐threatening otorhinolaryngological conditions.


title: Processing tissue and cells for transmission electron microscopy in diagnostic pathology and research

text: In transmission electron microscopy (TEM), electrons are transmitted through a plastic-embedded specimen, and an image is formed. TEM enables the resolution and visualization of detail not apparent via light microscopy, even when combined with immunohistochemical analysis. Ultrastructural examination of tissues, cells and microorganisms plays a vital role in diagnostic pathology and biologic research. TEM is used to study the morphology of cells and their organelles, and in the identification and characterization of viruses, bacteria, protozoa and fungi. In this protocol, we present a TEM method for preparing specimens obtained in clinical or research settings, discussing the particular requirements for tissue and cell preparation and analysis, the need for rapid fixation and the possibility of analysis of tissue already fixed in formalin or processed into paraffin blocks. Details of fixation, embedding and how to prepare thin and semi-thin sections, which can be used for analysis complementary to that performed ultimately using TEM, are also described.


docid: brrovbgj

title: Highway investment in deindustrialization: A territorial analysis of office property transactions in Hong Kong, 2002–2013

text: Abstract Transportation investment continues to grow in aid of economic competitiveness and environmental sustainability worldwide, but limited empirical research has been conducted on the changing value of highway investment in deindustrializing economies. This study examines the influences of highway proximity and traffic on office values in Hong Kong using hedonic price analysis on 13,670 transactions around highway interchanges for 2002–2013. Our hedonic regressions, controlling for unobservable district effects and incorporating instrumental variables, reveal that the associations of highway proximity and traffic with office prices appear to exhibit mixed results across Hong Kong's three territorial divisions. The negative externalities generated by excess traffic cancel out the accessibility benefits of highway proximity on Hong Kong Island, where densely built-up office districts are suited for amenity-sensitive knowledge businesses that tend to create value-added services through face-to-face communications. By contrast, highway proximity uplifts the value of office properties with lower transportation costs and higher market accessibility in Kowloon and the New Territories, where spacious workplaces near hub-port and logistics facilities are advantageous for mobility-driven trade and transportation businesses that tend to increase value-added throughput in cross-border relations with mainland China. These territorial findings are of particular importance for progressive policymakers to deploy the strategic applications of underground bypasses, greenway creation, interchange improvement, congestion charges, and smart technology to manage mobility and alleviate disamenity, accompanied by supportive public transit services and adaptive land-use rezoning, in the dynamic and complex process of deindustrialization.


title: Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study

text: BACKGROUND: There are few primary care studies of the COVID-19 pandemic. We aimed to identify demographic and clinical risk factors for testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre primary care network. METHODS: We analysed routinely collected, pseudonymised data for patients in the RCGP Research and Surveillance Centre primary care sentinel network who were tested for SARS-CoV-2 between Jan 28 and April 4, 2020. We used multivariable logistic regression models with multiple imputation to identify risk factors for positive SARS-CoV-2 tests within this surveillance network. FINDINGS: We identified 3802 SARS-CoV-2 test results, of which 587 were positive. In multivariable analysis, male sex was independently associated with testing positive for SARS-CoV-2 (296 [18·4%] of 1612 men vs 291 [13·3%] of 2190 women; adjusted odds ratio [OR] 1·55, 95% CI 1·27–1·89). Adults were at increased risk of testing positive for SARS-CoV-2 compared with children, and people aged 40–64 years were at greatest risk in the multivariable model (243 [18·5%] of 1316 adults aged 40–64 years vs 23 [4·6%] of 499 children; adjusted OR 5·36, 95% CI 3·28–8·76). Compared with white people, the adjusted odds of a positive test were greater in black people (388 [15·5%] of 2497 white people vs 36 [62·1%] of 58 black people; adjusted OR 4·75, 95% CI 2·65–8·51). People living in urban areas versus rural areas (476 [26·2%] of 1816 in urban areas vs 111 [5·6%] of 1986 in rural areas; adjusted OR 4·59, 95% CI 3·57–5·90) and in more deprived areas (197 [29·5%] of 668 in most deprived vs 143 [7·7%] of 1855 in least deprived; adjusted OR 2·03, 95% CI 1·51–2·71) were more likely to test positive. People with chronic kidney disease were more likely to test positive in the adjusted analysis (68 [32·9%] of 207 with chronic kidney disease vs 519 [14·4%] of 3595 without; adjusted OR 1·91, 95% CI 1·31–2·78), but there was no significant association with other chronic conditions in that analysis. We found increased odds of a positive test among people who are obese (142 [20·9%] of 680 people with obesity vs 171 [13·2%] of 1296 normal-weight people; adjusted OR 1·41, 95% CI 1·04–1·91). Notably, active smoking was linked with decreased odds of a positive test result (47 [11·4%] of 413 active smokers vs 201 [17·9%] of 1125 non-smokers; adjusted OR 0·49, 95% CI 0·34–0·71). INTERPRETATION: A positive SARS-CoV-2 test result in this primary care cohort was associated with similar risk factors as observed for severe outcomes of COVID-19 in hospital settings, except for smoking. We provide evidence of potential sociodemographic factors associated with a positive test, including deprivation, population density, ethnicity, and chronic kidney disease. FUNDING: Wellcome Trust.


title: Reference Genes for the Normalization of Gene Expression in Eucalyptus Species

text: Gene expression analysis is increasingly important in biological research, with reverse transcription–quantitative PCR (RT–qPCR) becoming the method of choice for high-throughput and accurate expression profiling of selected genes. Considering the increased sensitivity, reproducibility and large dynamic range of this method, the requirements for proper internal reference gene(s) for relative expression normalization have become much more stringent. Given the increasing interest in the functional genomics of Eucalyptus, we sought to identify and experimentally verify suitable reference genes for the normalization of gene expression associated with the flower, leaf and xylem of six species of the genus. We selected 50 genes that exhibited the least variation in microarrays of E. grandis leaves and xylem, and E. globulus xylem. We further performed the experimental analysis using RT–qPCR for six Eucalyptus species and three different organs/tissues. Employing algorithms geNorm and NormFinder, we assessed the gene expression stability of eight candidate new reference genes. Classic housekeeping genes were also included in the analysis. The stability profiles of candidate genes were in very good agreement. PCR results proved that the expression of novel Eucons04, Eucons08 and Eucons21 genes was the most stable in all Eucalyptus organs/tissues and species studied. We showed that the combination of these genes as references when measuring the expression of a test gene results in more reliable patterns of expression than traditional housekeeping genes. Hence, novel Eucons04, Eucons08 and Eucons21 genes are the best suitable references for the normalization of expression studies in the Eucalyptus genus.


title: An Evolving Approach to the Laboratory Assessment of COVID‐19

text: As the COVID‐19 outbreak has evolved in each country, the approach to the laboratory assessment of SARS‐CoV‐2 infection has had to evolve as well. This review addresses the evolving approach to the laboratory assessment of COVID‐19 and discusses how algorithms for testing have been driven, in part, by the demand for testing overwhelming the capacity to accomplish such testing. This review focused on testing in the United States as this testing is evolving whereas in China and other countries such as South Korea testing is widely available and includes both molecular testing for SARS‐CoV‐2 as well as serological testing using both ELISA methodology and lateral flow immunoassay methodology. Although commercial testing systems are becoming available, there will likely be insufficient numbers of such tests due to high demand. Serological testing will be the next testing issue as the COVID‐19 begins to subside. This will allow immunity testing as well as will allow the parameters of the COVID‐19 outbreak to be defined. This article is protected by copyright. All rights reserved.


title: Host responses from innate to adaptive immunity after vaccination: Molecular and cellular events

text: The availability of effective vaccines has had the most profound positive effect on improving the quality of public health by preventing infectious diseases. Despite many successful vaccines, there are still old and new emerging pathogens against which there is no vaccine available. A better understanding of how vaccines work for providing protection will help to improve current vaccines as well as to develop effective vaccines against pathogens for which we do not have a proper means to control. Recent studies have focused on innate immunity as the first line of host defense and its role in inducing adaptive immunity; such studies have been an intense area of research, which will reveal the immunological mechanisms how vaccines work for protection. Toll-like receptors (TLRs), a family of receptors for pathogen-associated molecular patterns on cells of the innate immune system, play a critical role in detecting and responding to microbial infections. Importantly, the innate immune system modulates the quantity and quality of longterm T and B cell memory and protective immune responses to pathogens. Limited studies suggest that vaccines which mimic natural infection and/or the structure of pathogens seem to be effective in inducing long-term protective immunity. A better understanding of the similarities and differences of the molecular and cellular events in host responses to vaccination and pathogen infection would enable the rationale for design of novel preventive measures against many challenging pathogens.


title: Emerging and Reemerging Virus Diseases of Vertebrates☆

text: Abstract In the last two decades, a large number of new viruses have been discovered, many of which are pathogenic in humans or other vertebrates. Among the more important causes of virus emergence have been changes in human behavior, population, and increases in travel to distant countries. In addition, the application of new molecular technologies has led to the recognition of many viruses that hitherto went undetected. Many of the new, emerging viruses have an RNA genome, and many are zoonoses. The spread of human immunodeficiency virus, causing acquired immune deficiency syndrome, and the use of immunosuppressive drugs following transplant surgery, have increased the numbers of people in the population that are highly susceptible to emerging virus infections. The threat of a new pandemic of influenza virus in the human population stresses the need for development of better methods for detection, surveillance, and control of emerging virus diseases.


title: Rapid and extraction-free detection of SARS-CoV-2 from saliva with colorimetric LAMP

text: Rapid, reliable, and widespread testing is required to curtail the ongoing COVID-19 pandemic. Current gold standard diagnostic assays are hampered by supply shortages in critical reagents including nasal swabs, RNA extraction kits, personal protective equipment (PPE), instrumentation, and labor. Here we present an approach to overcome these challenges with the development of a rapid colorimetric assay using reverse-transcription loop-mediated isothermal amplification (RT-LAMP) optimized on human saliva samples without an RNA purification step. We describe our optimizations of the LAMP reaction and saliva pre-treatment protocols that enabled rapid and sensitive detection of < 10(2) viral genomes per reaction in contrived saliva controls. We also observed high performance of this assay on a limited number of clinical saliva samples. While thorough validation on additional clinical samples will be needed before such an assay can be widely used, these preliminary results demonstrate a promising approach to overcome the current bottlenecks limiting widespread testing.


title: First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor [125I]RB 129

text: Abstract The selective and potent aminopeptidase N inhibitor [125I]RB 129 has been used for the radioautographic localization of this enzyme in rat brain, spinal cord and intestine. Brain microvessels and intestine brush-border cells were shown to present a high concentration of aminopeptidase N. Moreover, a labeling of various brain structures was observed. A very high level of binding occurred in the meninges, choroid plexus, pineal gland, paraventricular nucleus and pituitary gland. Moderate to high labeling was also observed in the cortex, caudate–putamen, subthalamic nucleus, central periaqueductal gray, thalamus, as well as in the dorsal and ventral horn of the spinal cord, which are known to contain a high concentration of enkephalins, opioid receptors and neutral endopeptidase. This co-localization confirms the physiological implication of aminopeptidase N in the inactivation of enkephalins accounting for the requirement of dual inhibition of neutral endopeptidase and aminopeptidase N to observe highly significant morphine-like effects induced by the protected endogenous opioid peptides. Aminopeptidase N was also visualized in moderate to high levels in other brain structures such as the hippocampus, nucleus accumbens, substantia nigra, hypothalamus (dorsomedial and ventromedial nuclei), raphe nucleus, pontine nucleus, inferior olive, and in high concentration in the granular layer of cerebellum. In summary, aminopeptidase N has been visualized for the first time in numerous brain areas using the selective inhibitor [125I]RB 129. This iodinated probe could allow the ex vivo and in vivo localization of aminopeptidase N in various tissues to be investigated and may also be used to evaluate quantitative changes in aminopeptidase N expression in pathological situations. Aminopeptidase N, which preferably removes NH2-terminal neutral amino acids from peptides, has probably a host of substrates. Nevertheless, a certain in vivo selectivity could be achieved by the presence of the enzyme in structures where the peptide effector and its receptors are also co-localized.


title: Influenza diagnosis and vaccination in Poland

text: Abstract In Poland between several thousand and several million cases of influenza and suspected influenza cases are registered, depending on the epidemic season. A variety of methods are available for the detection of the influenza viruses responsible for respiratory infection starting with the isolation of the virus in chick embryos or in cell lines such as MDCK, VERO, etc., and finishing with a variety of modifications of the classical PCR molecular biology such as PCR multiplex and Real-Time. The most effective way to combat influenza is through vaccination. Regular vaccination is one of the few steps that may be taken to protect individuals, especially in high-risk groups, from the potential and serious complications of influenza. In many countries, including Poland, despite the recommendations, the rate of vaccination against influenza is still low in all age groups. In the epidemic season 2011/2012, the level of distribution of the seasonal influenza vaccines was 4.5% of the population.


title: Chapter 5 John Snow, Cholera, the Broad Street Pump; Waterborne Diseases Then and Now

text: Abstract Cholera was a major global scourge in the 19th century, with frequent large-scale epidemics in European cities primarily originating in the Indian subcontinent. John Snow conducted pioneering investigations on cholera epidemics in England and particularly in London in 1854 in which he demonstrated that contaminated water was the key source of the epidemics. His thorough investigation of an epidemic in the Soho district of London led to his conclusion that contaminated water from the Broad Street pump was the source of the disease and, consequently, the removal of the handle led to cessation of the epidemic. He further studied cholera in London homes that were receiving water from two water supply systems; one from the sewage contaminated portion of the Thames River and the other that drew its water upstream from an uncontaminated part of the river. Rates of infection among clients of the distribution system drawing contaminated water far exceeded the, rates among those served by the company whose water intake was from above the contaminated section of the river. This demonstration reinforced the goals of the sanitation movement, which developed sewage drainage systems and water purification systems in cities and towns in the following decades, therewith vastly reducing the threats of cholera, typhoid and many other waterborne diseases. Despite progress being made globally, the public health problems of waterborne disease, including cholera, are by no means gone today, even in high-income countries. The tragic introduction of cholera after the earthquake devastation in Haiti in 2010 resulted in many thousands of cases and deaths from cholera indicating the still-present dangers of diseases spread into disaster situations. Cholera and other waterborne diseases remain some of the heaviest burdens of disease and death in low-income countries, especially after natural disasters or warfare as in Yemen in 2017 and are continuing challenges for global health.


docid: lwnkubnz

title: The C-Terminal Portion of the Nucleocapsid Protein Demonstrates SARS-CoV Antigenicity

text: In order to develop clinical diagnostic tools for rapid detection of SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal portion of the nucleocapsid (NC) gene was amplified using RT-PCR from the SARS-CoV genome, cloned into a yeast expression vector (pEGH), and expressed as a glutathione S-transferase (GST) and Hisx6 double-tagged fusion protein under the control of an inducible promoter. Western analysis on the purified protein confirmed the expression and purification of the NC fusion proteins from yeast. To determine its antigenicity, the fusion protein was challenged with serum samples from SARS patients and normal controls. The NC fusion protein demonstrated high antigenicity with high specificity, and therefore, it should have great potential in designing clinical diagnostic tools and provide useful information for vaccine development.


title: Canine parvovirus vaccine elicits protection from the inflammatory and clinical consequences of the disease

text: Abstract Inflammatory changes following infection are central to the clinical manifestation of disease. However, information regarding such changes in animal disease is limited. In canine parvovirus infected puppies we measured the levels of acute phase proteins and changes in leukocyte phenotypes and cell trafficking by flow cytometry. These parameters correlated with conventional assessment of clinical disease in a vaccine efficacy study. Seropositive (CPV-2) 6-week-old puppies given three doses of a CPV-2 containing vaccine developed significant antibody titers and remained healthy after experimental infection with CPV-2b. Unvaccinated controls developed clinical signs and shed virus. Importantly, acute phase proteins became elevated, and lymphopenia, neutropenia and modulation of neutrophil-CD4 were detected in controls but not in vaccinates.


title: Vaccine supply, demand, and policy: A primer

text: Objective To provide an overview of supply and demand issues in the vaccine industry and the policy options that have been implemented to resolve these issues. Data sources Medline, Policy File, and International Pharmaceutical Abstracts were searched to locate academic journal articles. Other sources reviewed included texts on the topics of vaccine history and policy, government agency reports, and reports from independent think tanks. Keywords included vaccines, immunizations, supply, demand, and policy. Study selection Search criteria were limited to English language and human studies. Articles pertaining to vaccine demand, supply, and public policy were selected and reviewed for inclusion. Data extraction By the authors. Data synthesis Vaccines are biologic medications, therefore making their development and production more difficult and costly compared with “small-molecule” drugs. Research and development costs for vaccines can exceed $800 million, and development may require 10 years or more. Strict manufacturing regulations and facility upgrades add to these costs. Policy options to increase and stabilize the supply of vaccines include those aimed at increasing supply, such as government subsidies for basic vaccine research, liability protection for manufacturers, and fast-track approval for new vaccines. Options to increase vaccine demand include advance purchase commitments, government stockpiles, and government financing for select populations. Conclusion High development costs and multiple barriers to entry have led to a decline in the number of vaccine manufacturers. Although a number of vaccine policies have met with mixed success in increasing the supply of and demand for vaccines, a variety of concerns remain, including developing vaccines for complex pathogens and increasing immunization rates with available vaccines. New policy innovations such as advance market commitments and Medicare Part D vaccine coverage have been implemented and may aid in resolving some of the problems in the vaccine industry.


title: Maternal antibody to infectious bronchitis virus: its role in protection against infection and development of active immunity to vaccine

text: Abstract Chicks hatched with high levels of maternal antibody had excellent protection (>95%) against infectious bronchitis virus (IBV) challenge at 1 day of age, but not at 7 days (<30%). This protection significantly (P<0.05) correlated with levels of local respiratory antibody and not with serum antibody. A high percentage of both maternal antibody-positive (Mab+) and maternal antibody-negative (Mab−) chicks failed to produce IBV antibody when vaccinated at 1 day of age by the intraocular route. In addition, Mab+ chickens had a weaker virus-neutralizing antibody response to a second IBV vaccination compared to Mab− birds (P<0.05). Mab+ chicks experienced a more rapid decline (P<0.01) in maternal antibody after 1-day-of-age vaccination compared to their unvaccinated counterparts. A monoclonal antibody-based blocking ELISA that measured antibody levels specific to S1 glycoprotein of IBV correlated well with virus-neutralizing antibody titers.


title: History and epidemics in modern Asia Robert Peckham Epid

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Cost-Related Antihypertensive Medication Nonadherence: Action in the Time of COVID-19 and Beyond


title: Bioengineering and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection

text: Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent, high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed non-ribosomal peptide/polyketide origin in order to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of HBV, HCV and HIV-1 replication, shows minimal inhibition of major drug transporters and has a high barrier to generation of both HCV and HIV-1 resistance.


title: Effects of Laser Texture Oxidation and High-Temperature Annealing of TiV Alloy Thin Films on Mechanical and Antibacterial Properties and Cytotoxicity

text: Titanium dioxide and vanadium oxides have been applied extensively in industrial and medical fields. The objective of this study was to develop various composite structures of titanium and vanadium oxide (Ti-V-O) coatings on pure titanium through high-temperature annealing and laser texturing oxidation, separately; additionally, surface morphologies, tribological and hydrophilic properties, and antibacterial and biocompatibility abilities of these Ti-V-O coatings were evaluated. TiV alloy thin films were deposited on pure titanium and then annealed to form Ti-V-O coatings through thermal oxidation and laser texturing oxidation. Ball-on-disc wear tests and contact angle tests were conducted to evaluate the tribological properties and wettability of the coatings, respectively. The antibacterial activity of the coatings was estimated by SYTO9 nucleic acid staining with Staphylococcus aureus (Gram-positive bacteria). The cell cytotoxicity of the coatings was analyzed following the ISO 10995-5:2009 standard with human skin fibroblast cells. The Ti-V-O coatings, subjected to annealing at 700 °C, demonstrated higher hardness (Hv 1171) and a lower friction coefficient (0.6). The highest hardness (Hv 2711) and the lowest friction coefficient (0.52) were obtained for the Ti-V-O after laser surface texturing oxidation at 100 kHz. The oxide coating obtained from 100 kHz laser texturing oxidation exhibited the lotus effect because of its systematic textured microstructures, and displayed superhydrophobic surface properties. Compared with the unannealed TiV coating, both the samples with high-temperature annealing and laser surface texturing oxidation had excellent antibacterial properties to Staphylococcus aureus. However, the Ti-V-O thin films exhibited notable cell cytotoxicity. Although the cell viability on Ti-V-O coatings were not ideal, this study confirmed improvement in surface hardness, tribology, and antibacterial performance in Ti-V-O coatings, which may have potential for use in biomedical tools, devices, and equipment.


docid: befehafo

title: Amantadine as a drug to mitigate the effects of COVID-19

text: Abstract The SARS-CoV-2 virus has spread around the world. At this time, there is no vaccine that can help people prevent the spread of coronavirus. We are proposing amantadine as a drug that can be used to mitigate the effects of the virus. It is demonstrated by docking models how amantadine can exert its action on Coronavirus viroporin E.


title: Development of a molecular assay for the general detection of tospoviruses and the distinction between tospoviral species

text: A Luminex xTAG-based assay for plant-infecting tospoviruses was developed. The test enables the detection of tospoviruses in general and the differentiation of the four important member species of this genus: Tomato spotted wilt virus, Impatiens necrotic spot virus, the proposed ‘Capsicum chlorosis virus’ and Watermelon silver mottle virus. The generic tospovirus primers used in this method are also applicable for detection of tospoviruses by basic RT-PCR. We also describe an economic alternative method for the distinction of the four tospoviruses mentioned and of additional member viruses, based on a restriction fragment length polymorphism (RFLP). The sophisticated Luminex xTAG technology allows the simultaneous detection of various targets. This study is part of a project that aims to develop a method for the simultaneous detection of various plant pathogens (viral, bacterial and fungal) in plant material.


title: The clinical impact of coronavirus infection in patients with hematologic malignancies and hematopoietic stem cell transplant recipients

text: Abstract Background Compared to other respiratory viruses, relatively little is known about the clinical impact of coronavirus (CoV) infection after hematopoietic stem cell transplant (HSCT) or in patients with hematologic malignancies. Objectives To characterize the role of CoV in respiratory tract infections among HSCT and hematologic malignancy patients. Study design We conducted a retrospective review of all cases of CoV infection documented by polymerase chain reaction, (PCR)-based testing on nasopharyngeal and bronchoalveolar lavage fluid samples between June 2010 and 2013. Cases of CoV infection occurring in HSCT and hematologic malignancy patients were identified and the clinical characteristics of these cases were compared to other respiratory viruses. Results CoV was identified in 2.6% (n =43) of all samples analyzed (n =1661) and in 6.8% of all samples testing positive for a respiratory virus (n =631). 33 of 38 (86.8%) of patients in whom CoV was identified were HSCT and hematologic malignancy patients. Among these patients, CoV was detected in 9.7% of unique infection episodes, with only rhinovirus/enterovirus (RhV/EnV) infection being more common. Group I CoV subtypes accounted for 76.3% of cases, and 57% of infections were diagnosed between December and March. CoV infection was associated with upper respiratory tract symptoms in most patients, similar to other respiratory viruses. Possible and proven lower respiratory tract disease was less common compared to other respiratory viruses except RhV/EnV. Conclusions CoV is frequently detected in HSCT and hematologic malignancy patients in whom suspicion for a respiratory viral infection exists, but is less likely to progress to lower respiratory tract disease than most other respiratory viruses.


title: Houttuynia cordata inhibits lipopolysaccharide-induced rapid pulmonary fibrosis by up-regulating IFN-γ and inhibiting the TGF-β1/Smad pathway

text: Abstract This study aimed to explore the effect and mechanism of H. cordata vapor extract on acute lung injury (ALI) and rapid pulmonary fibrosis (RPF). We applied the volatile extract of HC to an RPF rat model and analyzed the effect on ALI and RPF using hematoxylin–eosin (H&E) staining, routine blood tests, a cell count of bronchoalveolar lavage fluid (BALF), lactate dehydrogenase (LDH) content, van Gieson (VG) staining, hydroxyproline (Hyp) content and the dry/wet weight ratio. The expression of IFN-γ/STAT1, IL-4/STAT6 and TGF-β1/Smads was analyzed using ELISA, immunohistochemistry and western blotting methods. The active ingredients of the HC vapor extract were analyzed using a gas chromatograph–mass spectrometer (GC–MS), and the effects of the active ingredients of HC on the viability of NIH/3T3 and RAW264.7 cells were detected using an MTT assay. The active ingredients of the HC vapor extract included 4-terpineol, α-terpineol, l-bornyl acetate and methyl-n-nonyl ketone. The results of the lung H&E staining, Hyp content, dry/wet weight ratio and VG staining suggested that the HC vapor extract repaired lung injury and reduced RPF in a dose-dependent manner and up-regulated IFN-γ and inhibited the TGF-β1/Smad pathway in vivo. In vitro, it could inhibit the viability of RAW264.7 and NIH/3T3 cells. It also dose-dependently inhibited the expression of TGF-β1 and enhanced the expression of IFN-γ in NIH/3T3. The HC vapor extract inhibited LPS-induced RPF by up-regulating IFN-γ and inhibiting the TGF-β1/Smad pathway.


title: Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

text: Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases.


title: Impact of COVID-19 on academic activities and way forward in Indian Optometry

text: Abstract Purpose Academia is experiencing massive reforms globally amid lockdown in COVID-19 outbreak. This study is aimed to apprehend the enabling and impeding factors of these reforms, with a focus on optometry education. It brings together how the Indian optometry educational system has responded to COVID-19 disruptions with findings of the 2020 survey, in light of similar survey done in 2018. Methodology A cross-sectional survey was designed to find changes in optometry training and adaptations of Indian optometry educators amid COVID 19 lockdown. In the last week of April 2020, on the observation that the majority of optometry institutions have switched their teaching-learning activities on e-learning mode, an online survey was conducted using a validated questionnaire containing a mix of open and close-ended questions. Results Seventy-three out of 78 optometry educators (93.58%) have switched to e-learning mode in a very short time span with good confidence. Most teaching-learning and assessment activities are carried out using multi-device supporting video conferencing tools, dedicated educational portals and social media apps. Conclusion The COVID-19 pandemic is proving to be constructive disruptor, giving an opportunity for restructuring the present conventional, classroom based educational system. The quick transitions to online mode assisted in keeping continuity of optometry education programs, effectively fitting in the purpose of completion of the current academic year. The rapid transition to online education has not only benefited optometry students but also has created a momentum of continued education for practicing optometrist in the country.


title: Full-Genome Deep Sequencing and Phylogenetic Analysis of Novel Human Betacoronavirus

text: A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient’s sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events.


title: Molecular Bases and Role of Viruses in the Human Microbiome

text: Abstract Viruses are dependent biological entities that interact with the genetic material of most cells on the planet, including the trillions within the human microbiome. Their tremendous diversity renders analysis of human viral communities (“viromes”) to be highly complex. Because many of the viruses in humans are bacteriophage, their dynamic interactions with their cellular hosts add greatly to the complexities observed in examining human microbial ecosystems. We are only beginning to be able to study human viral communities on a large scale, mostly as a result of recent and continued advancements in sequencing and bioinformatic technologies. Bacteriophage community diversity in humans not only is inexorably linked to the diversity of their cellular hosts but also is due to their rapid evolution, horizontal gene transfers, and intimate interactions with host nucleic acids. There are vast numbers of observed viral genotypes on many body surfaces studied, including the oral, gastrointestinal, and respiratory tracts, and even in the human bloodstream, which previously was considered a purely sterile environment. The presence of viruses in blood suggests that virome members can traverse mucosal barriers, as indeed these communities are substantially altered when mucosal defenses are weakened. Perhaps the most interesting aspect of human viral communities is the extent to which they can carry gene functions involved in the pathogenesis of their hosts, particularly antibiotic resistance. Persons in close contact with each other have been shown to share a fraction of oral virobiota, which could potentially have important implications for the spread of antibiotic resistance to healthy individuals. Because viruses can have a large impact on ecosystem dynamics through mechanisms such as the transfers of beneficial gene functions or the lysis of certain populations of cellular hosts, they may have both beneficial and detrimental roles that affect human health, including improvements in microbial resilience to disturbances, immune evasion, maintenance of physiologic processes, and altering the microbial community in ways that promote or prevent pathogen colonization.


title: Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode

text: A 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. He was sexually disinhibited with pressured speech and grandiose ideas. His behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. Investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neuroimaging and a lumbar puncture were normal. Initial screening for SARS-CoV-2 in the cerebrospinal fluid was negative although no validated assay was available. The patient’s mental state remained abnormal following stepdown from intensive care. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid.


title: Chapter 5 Future prospects

text: Abstract Cryo-electron microscopy (cryo-EM) in combination with single-particle analysis has begun to complement crystallography in the study of large macromolecules at near-atomic resolution. Furthermore, advances in cryo-electron tomography have made possible the study of macromolecules within their cellular environment. Single-particle and tomographic studies will become even more useful when technologies for improving the signal-to-noise ratio such as direct electron detectors and phase plates become widely available. Automated image acquisition has significantly reduced the time and effort required to determine the structures of macromolecular assemblies. As a result, the number of structures determined by cryo-EM is growing exponentially. However, there is an urgent need for improved criteria for validating both the reconstruction process and the atomic models derived from cryo-EM data. Another major challenge will be mitigating the effects of anisotropy caused by the missing wedge and the excessively low signal-to-noise ratio for tomographic data. Parallels between the development of macromolecular crystallography and cryo-EM have been used to tentatively predict the future of cryo-EM.


Anti-CD20 and Covid-19 in Multiple Sclerosis and related disorders: a case series of 60 patients from Madrid, Spain


Effective health communication – a key factor in fighting the COVID-19 pandemic


title: Functional cell models of the gut and their applications in food microbiology — A review

text: Abstract Animal experimentation has a long tradition for risk assessment of new drugs before they reach the clinic. To reduce expensive animal experimentation, attempts have been made to build inexpensive and convenient intestinal functional cell models to study toxicity and bioavailability of new substances along with providing relevant models to study interactions between the host, pathogens and intestinal microflora. We review the available cell lines and models of the intestine and their potential uses. Tumor derived cell lines such as Caco-2, T84 and HT-29 are widely used despite many drawbacks, which are discussed with respect to complexity of the gut, where various cell types interact with commensal microbiota and gut-associated lymphoid tissue. To address this complexity, 3D models of human and animal gut represent a promising in vitro system to mimic in vivo situation without the use of transformed cell lines.


title: HMPV in Immunocompromised Patients: Frequency and Severity in Pediatric Oncology Patients

text: Cancer is the first cause of death by disease in childhood globally. The most frequent types of cancers in children and adolescents are leukemias, followed by brain and central nervous system tumors and lymphomas. The recovery rate of cancer in children is around 80% in developed countries and up to 30% in developing countries. Some of the main causes of complications in children and adolescents with cancer are respiratory viral infections, mainly in bone marrow-transplanted patients. Respiratory viruses have been detected in the bronchoalveolar lavage or nasal wash specimens from cancer patients with or without respiratory illness symptoms. Human metapneumovirus (HMPV) is within the ten most common viruses that are encountered in samples from pediatric patients with underlying oncology conditions. In most of cases, HMPV is found as the only viral agent, but co-infection with other viruses or with bacterial agents has also been reported. The discrepancies between the most prevalent viral agents may be due to the different populations studied or the range of viral agents tested. Some of the cases of infection with HMPV in cancer patients have been fatal, especially in those who have received a hematopoietic stem cell transplant. This review seeks to show a general view of the participation of HMPV in respiratory illness as a complication of cancer in childhood and adolescence.


title: Cerebellar Scholars’ Challenging Time in COVID-19 Pandemia

text: Novel coronavirus, SARS-CoV2, has caused pandemic of highly contagious disease called coronavirus disease 2019 (COVID-19), with epicenters in China, Italy, Spain, and the USA. Primarily affecting the human respiratory system, SARS-CoV2 has some impact on the human brain, but apparently minimal on the cerebellum, at least so far. Neurological involvement in the acute phase appears to manifest with confusion, dizziness, impaired consciousness, propensity to develop acute strokes, anosmia, hypogeusia, ataxia, epilepsy, and neuralgia. Cerebellar scholars are facing a time of uncertainty. Telemedicine has suddenly emerged as an alternative to follow patients. There is an urgent need to develop novel platforms to assess and follow ataxic patients remotely, especially because cerebellar patients often require ambulatory care to maintain their autonomy.


What Have We Learned about Nursing from the Coronovirus Pandemic


title: Study of influential factors of provincial health expenditure -analysis of panel data after the 2009 healthcare reform in China

text: BACKGROUND: Total Healthcare Expenditure (THE) has increased substantially in all countries. Since the health system reform and health policy environment differ from each country, it is necessary to analyze the motivations of THE in a specific country. METHODS: The objective of this study was to analyze the influential factors of Provincial THE (PTHE) per capita in China by using spatiotemporal panel data across 31 provinces (including provinces, autonomous regions, and municipalities, all called provinces in here) from 2009 to 2016 at the provincial and annual level. Generalized Estimating Equation (GEE) was used to identify the influential factors of PTHE per capita. RESULTS: The number of beds per 10,000 population explained most of the variation of PTHE per capita. The results also showed that health expenditure in China reacts more to mortality compared with the Gross Domestic Product (GDP) per capita. But mortality and Out-Of-Pocket Payments (OOP) as a percentage of THE were associated with PTHE per capita negatively. The rate of infectious diseases and THE as a percentage of GDP had no statistical significance. And the Proportion of the Population Aged 65 and Over (POP65) impact PTHE per capita positively. But the coefficient was small. CONCLUSIONS: In response to these findings, we conclude that the impact of the increasing percentage of OOP in THE diminishes the PTHE. Furthermore, we find that both the “baseline” health level and health provision are positively correlated with PTHE, which outweighs the effect of GDP.


title: Dental care and infection-control procedures during the COVID-19 pandemic: the experience in Taipei City Hospital, Taiwan

text: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now widely spread globally. The main transmission routes of SARS-CoV-2 comprise human-to-human droplet infection, including inhalation and contact infection of patient’s saliva, blood and other body fluids through oral mucosa, nasal mucosa, and the eyes, and orofecal transmission. Dental treatment necessitates close-proximity, face-to-face practices and can generate droplets or aerosols containing water, saliva, blood, microorganisms, and other debris during the procedure. Therefore, dental professionals are at a high risk of SARS-CoV-2 infection. To prevent nosocomial SARS-CoV-2 spread during dental procedures, Taipei City Hospital established a dental patient triage and workflow algorithm for the provision of dental services during the COVID-19 pandemic. Given the highly contagious nature of SARS-CoV-2, it is imperative to institute an appropriate standard procedural policy for patient management and recommendation of dental treatment at hospitals during the COVID-19 pandemic.


title: SHAPE analysis of the RNA secondary structure of the Mouse Hepatitis Virus 5’ untranslated region and N-terminal nsp1 coding sequences

text: Abstract SHAPE technology was used to analyze RNA secondary structure of the 5′ most 474 nts of the MHV-A59 genome encompassing the minimal 5′ cis-acting region required for defective interfering RNA replication. The structures generated were in agreement with previous characterizations of SL1 through SL4 and two recently predicted secondary structure elements, S5 and SL5A. SHAPE provided biochemical support for four additional stem–loops not previously functionally investigated in MHV. Secondary structure predictions for 5′ regions of MHV-A59, BCoV and SARS-CoV were similar despite high sequence divergence. The pattern of SHAPE reactivity of in virio genomic RNA, ex virio genomic RNA, and in vitro synthesized RNA was similar, suggesting that binding of N protein or other proteins to virion RNA fails to protect the RNA from reaction with lipid permeable SHAPE reagent. Reverse genetic experiments suggested that SL5C and SL6 within the nsp1 coding sequence are not required for viral replication.


title: Emerging Adults and COVID-19: The Role of Individualism-Collectivism on Perceived Risks and Psychological Maladjustment

text: The outbreak of the coronavirus disease 2019 (COVID-19) has dramatically changed our habits and routines. Uncertainty, insecurity, instability for the present and future, and reduced autonomy and self-directedness, are common feelings at the time of COVID-19. These aspects are very important during emerging adulthood. In spite of the fact that medical reports suggest that youth are less prone to experience COVID-19 infections, emerging adults might be at higher risk for their psychological adjustment. Emerging adults showed higher concerns about their role as a possible asymptomatic carrier than being positive with COVID-19 themselves. Both worries and concerns about COVID-19 and psychological maladjustment may be related to cultural factors. Individualism, collectivism, equality, and hierarchy seem to be meaningful perspectives to take into account. A total of 1183 Italian emerging adults were asked to fill out an online survey during the second week of the national lockdown in Italy. Results showed they reported an accurate perceived knowledge about COVID-19. At the same time, they showed higher worries and concerns about COVID-19 for their relatives, followed by more general/social worries. The lowest score included worries about COVID-19 related to themselves. State anxiety and stress levels were above the normal cutoff, confirming the challenges that emerging adults are facing during the pandemic. On one hand, emerging adults’ collectivistic orientation was related to higher perceived risks of infection; on the other hand, it predicted lower psychological maladjustment, controlling for socio-demographic variables. The study suggests that to fight the COVID-19 pandemic and decrease levels of psychological maladjustment in emerging adulthood, individuals’ cultural orientation such as the wish of sharing common goals with others, interdependence, and sociability, have to be emphasized and promoted as protective factors.


title: Preparedness and the importance of meeting the needs of healthcare workers: a qualitative study on Ebola

text: Summary Background Healthcare workers (HCWs) face specific challenges in infectious disease outbreaks, which provide unusual, new events with exposure risk. The fear of infection or new, unknown tasks in an unfamiliar setting, for example, may complicate outbreak management. Aim To gain insight into how healthcare organizations can prepare to meet the needs of their HCWs by capturing the experiences of HCWs with patients with suspected Ebola virus disease. Methods We conducted 23 in-depth interviews with HCWs, of whom 20 worked in a Dutch university hospital and three worked in a regional ambulance service. We invited HCWs who cared for patients with suspected Ebola or who were on the team preparing for admission of such patients in the period 2014–2015. Findings The HCWs were stressed and anxious, but most rated their overall experience as positive. We categorized the reported experiences in three main themes, namely, experiences related to: (i) the novelty of the threat, (ii) the risk of infection and fear of transmission, and (iii) the excessive attention. Our results underline the importance of a supportive working environment suitable for crises. Conclusion The experiences of HCWs dealing with patients with suspected Ebola can direct improvements in generic preparedness for highly transmissible diseases.


title: Transforming ophthalmic education into virtual learning during COVID-19 pandemic: a global perspective

text: OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has imposed measures of social distancing and barriers in delivery of “in person” education. Institutions, involved in training the next generation of ophthalmologists, are using alternative teaching methods to maintain the standard of education. METHODS: We conducted a worldwide survey among physicians, who are actively involved in Ophthalmology-related education, between 3 and 14 April 2020. The expert survey, developed on the basis of literature search and focus group discussions, comprised 23 questions addressing the use of e-learning in Ophthalmology during the COVID-19 pandemic. RESULTS: A total of 321 participants from both academic and non-academic institutions worldwide, with variable practice experience and expertise, completed the survey. Before the pandemic, the majority of participants used traditional training modalities, including lectures, grand rounds and journal clubs, and 48% did not use any e-learning. There was a statistically significant increase in the use of all e-learning alternatives during the pandemic (p < 0.001), associated mainly with the availability of e-learning facilities (p < 0.001) and the academic character of institutions (p < 0.001). Zoom® was recognized as the mostly used platform for virtual teaching. Although theoretical teaching may take place, the surgical training of residents/fellows was dramatically reduced. The latter was significantly associated with participants’ perspectives about teaching practices (p < 0.001). CONCLUSION: COVID-19 pandemic imposed great challenges in the educational field of Ophthalmology. The experience related to virtual training in Ophthalmology, gained during the pandemic, may change the traditional teaching practices in the world and provide new educational opportunities.


title: Global dynamics for an SIR patchy model with susceptibles dispersal

text: An [Formula: see text] epidemiological model with suscptibles dispersal between two patches is addressed and discussed. The basic reproduction numbers [Formula: see text] and [Formula: see text] are defined as the threshold parameters. It shows that if both [Formula: see text] and [Formula: see text] are below unity, the disease-free equilibrium is shown to be globally asymptotically stable by using the comparison principle of the cooperative systems. If [Formula: see text] is above unity and [Formula: see text] is below unity, the disease persists in the first patch provided [Formula: see text]. If [Formula: see text] is above unity, [Formula: see text] is below unity, and [Formula: see text], the disease persists in the second patch. And if [Formula: see text] and [Formula: see text] are above unity, and further [Formula: see text] and [Formula: see text] are satisfied, the unique endemic equilibrium is globally asymptotically stable by constructing the Lyapunov function. Furthermore, it follows that the susceptibles dispersal in the population does not alter the qualitative behavior of the epidemiological model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1687-1847-2012-131) contains supplementary material, which is available to authorized users.


title: Cervical lymphoid tissue but not the central nervous system supports proliferation of virus-specific T lymphocytes during coronavirus-induced encephalitis in rats

text: Abstract The CD4+ T lymphocyte response in the central nervous system (CNS) and cervical lymph nodes (CLNs) of rats with different susceptibility to coronavirus-induced encephalitis was investigated. The majority of CD4+ T lymphocytes entering the virus-infected CNS in the course of the infection are primed cells that neither proliferate ex vivo nor can be stimulated to proliferation by viral antigens or mitogen in vitro. In contrast, T lymphocytes taken from CLNs of the same animals revealed a strong proliferative response. Restimulation of CLN lymphocytes by viral antigens disclosed a striking difference between the disease-resistant rat strain Brown Norway (BN) and the susceptible Lewis (LEW) strain. Whereas BN lymphocytes responded as early as 5 days post infection, it took more than 11 days until a comparable proliferation was detectable in LEW lymphocytes. From these data we postulate that the majority of T lymphocytes entering the virus-infected brain after sensitisation and expansion in cervical lymph nodes is unresponsive to further proliferation signals and that the kinetics and magnitude of T lymphocyte stimulation in CLNs play an important role in the clinical course of the infection.


title: Inhibition of the PI3K/Akt pathway by Ly294002 does not prevent establishment of persistent Junín virus infection in Vero cells

text: In previous work, we demonstrated that the arenavirus Junín virus (JUNV) is able to activate Akt by means of the phosphatidylinositol-3-kinase (PI3K) survival pathway during virus entry. This work extends our study, emphasizing the relevance of this pathway in the establishment and maintenance of persistent infection in vitro. During the course of infection, JUNV-infected Vero cells showed a typical cytopathic effect that may be ascribed to apoptotic cell death. Treatment of infected cultures with Ly294002, an inhibitor of the PI3K/Akt pathway, produced an apoptotic response similar to that observed for uninfected cells treated with the drug. This result suggests that virus-induced activation of the PI3K/Akt pathway does not deliver a strong enough anti-apoptotic signal to explain the low proportion of apoptotic cells observed during infection. Also, inhibition of the PI3K/Akt pathway during the acute stage of infection did not prevent the establishment of persistence. Furthermore, treatment of persistently JUNV-infected cells with Ly294002 did not alter viral protein expression. These findings indicate that despite the positive modulation of the PI3/Akt pathway during Junín virus entry, this would not play a critical role in the establishment and maintenance of JUNV persistence in Vero cells.


title: A simple and compact smartphone-based device for the quantitative readout of colloidal gold lateral flow immunoassay strips

text: Abstract Colloidal gold lateral flow immunoassay strips (AuNPs-LFIS) have been widely applied as qualitative diagnostic tools for point-of-care tests (POCT). If strip readers were incorporated, their use could be extended to quantitative analysis. However, their cost and non-portability render commercial strip readers unavailable for use in either home testing, community or rural hospital diagnosis. This is particularly true for on-site testing. Here, a smartphone-based reader was designed and 3D-printed for quantitatively assess AuNPs-LFIS. The basic principle of the devise was relying on a smartphone’s ambient light sensor (SPALS). This sensor was harnessed to measure the transmitted light intensities originating from the T-lines on the strips, the transmitted light intensities vary with concentration of AuNP on the T-lines. To validate this approach, our newly developed smartphone’s ambient light sensor-based reader (SPALS-reader) was used to readout AuNPs-LFIS of three analytical targets: cadmium ion (Cd2+; limit of detection (LOD) was 0.16 ng/mL), clenbuterol (CL; LOD was 0.046 ng/mL), and porcine epidemic diarrhea virus (PEDV; LOD was 0.055 μg/mL). The result showed good consistency with the results of conventional image analysis approaches, indicating that the smartphone-based device is appropriate for use in AuNPs-LFIS readouts. Compared with the traditional analysis method, the developed AuNPs-LFIS reader is easier operated, lower cost and more portable, which provided an on-site quantitative analysis tool for AuNPs-LFIS and enhances the applied range of AuNPs-LFIS.


title: Human Streptococcus suis Outbreak, Sichuan, China

text: From mid-July to the end of August 2005, a total of 215 cases of human Streptococcus suis infections, 66 of which were laboratory confirmed, were reported in Sichuan, China. All infections occurred in backyard farmers who were directly exposed to infection during the slaughtering process of pigs that had died of unknown causes or been killed for food because they were ill. Sixty-one (28%) of the farmers had streptococcal toxic shock syndrome; 38 (62%) of them died. The other illnesses reported were sepsis (24%) and meningitis (48%) or both. All isolates tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef, and sly. A single strain of S. suis caused the outbreak, as shown by the identification of a single ribotype. The high death ratio was of concern; prohibiting backyard slaughtering ended the outbreak.


title: Assessment of putative protein targets derived from the SARS genome

text: The ability to rapidly and reliably develop hypotheses on the function of newly discovered protein sequences requires systematic and comprehensive analysis. Such an analysis, embodied within the DS GeneAtlas™ pipeline, has been used to critically evaluate the severe acute respiratory syndrome (SARS) genome with the goal of identifying new potential targets for viral therapeutic intervention. This paper discusses several new functional hypotheses on the roles played by the constituent gene products of SARS, and will serve as an example of how such assignments can be developed or extended on other systems of interest.


title: Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16–December 28, 2013

text: Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010–July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial collaboration are crucial to achieve the goal of rabies-free status in Taiwan.


title: Comparisons of viral shedding time of SARS-CoV-2 of different samples in ICU and non-ICU patients

text: • Dynamic RT-PCR test samples of nasal swabs, blood, fecal, urine, saliva and tears. • Nasal swab had a longer viral shedding time of SARS-CoV-2 than blood and saliva. • Viral shedding time of SARS-CoV-2 in ICU was longer than non-ICU patients.


COVID-19 and Pneumocystis jirovecii pneumonia: a diagnostic dilemma in HIV


docid: crabuenz

title: Protective effect of theaflavin on glycoprotein components and TCA cycle enzymes in high-fat diet and streptozotocin-induced diabetic rats

text: BACKGROUND: Theaflavins are major polyphenols in black tea which is the most widely consumed tea in the world. They possess a broad spectrum of biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardio-protective effects. The present study was aimed to evaluate the protective effect of theaflavin on glycoprotein content and tricorboxylic acid cycle enzymes in high-fat diet and streptozotocin-induced diabetic rats as there was no study on this aspect. Diabetes was induced in male albino Wistar rats by feeding them with high-fat diet and injecting them intraperitoneally with streptozotocin (40 mg/kg b.wt). RESULTS: Different doses of theaflavin (25, 50, and 100 mg/kg b.wt /day) were administered orally to high-fat diet and streptozotocin-induced diabetic rats for 30 days for fixing the glucose lowering dose. However, the dose at 100 mg/kg b.wt showed a significant reduction in the levels of plasma glucose and Homeostatic Model Assessment of Insulin Resistance with concomitant elevation of insulin when compared to the other two doses (25 and 50 mg/kg b.wt). Hence, 100 mg/kg b.wt was fixed as an effective dose and used for further analysis. Theaflavin administration restored the altered glycosylated hemoglobin, hemoglobin and glycoproteins (Hexose, hexosamine, fucose, and sialic acid) and TCA cycle enzymes (isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase) near the normal levels by correcting hyperglycemia. Improved histological changes were observed in the pancreas of diabetic rats upon treatment with theaflavin which supported the biochemicals investigated. CONCLUSION: The effect produced by the theaflavin on various parameters was comparable to that of metformin—a reference antidiabetic drug. These findings suggest that theaflavin can replace the commercial drugs which could lead to reduction in toxicity and side effect caused by the later as well as reduce the secondary completions.


Use of US to expedite diagnosis of PE in COVID-19 Patient


title: How do we assess hospital cleaning? A proposal for microbiological standards for surface hygiene in hospitals

text: Abstract Increasing numbers of hospital-acquired infections have generated much attention over the last decade. The public has linked the so-called ‘superbugs’ with their experience of dirty hospitals, but the precise role of cleaning in the control of these organisms in unknown. Hence the importance of a clean environment is likely to remain speculative unless it becomes an evidence-based science. This proposal is a call for bacteriological standards with which to assess clinical surface hygiene in hospitals, based on those used by the food industry. The first standard concerns any finding of a specific ‘indicator’ organism, the presence of which suggests a requirement for increased cleaning. Indicators would include Staphylococcus aureus, including methicillin-resistant S. aureus, Clostridium difficile, vancomycin-resistant enterococci and various Gram-negative bacilli. The second standard concerns a quantitative aerobic colony count of <5cfu/cm2 on frequent hand touch surfaces in hospitals. The principle relates to modern risk management systems such as HACCP, and reflects the fact that pathogens of concern are widespread. Further work is required to evaluate and refine these standards and define the infection risk from the hospital environment.


title: Chikungunya Fever in Travelers Returning to Europe from the Indian Ocean Region, 2006

text: Chikungunya fever has spread through several Indian Ocean islands and India, including popular travel destinations. To compare usefulness of diagnostic tests and to understand reasons for the magnitude and severity of an outbreak, we used 3 diagnostic methods to test 720 samples from 680 patients returning to Europe from the Indian Ocean region in 2006. Chikungunya infection was confirmed for 24.4% patients in the first half of the year and for 9.9% in the second half. Reverse transcription–PCR was positive for all samples taken up to day 4 after symptom onset. Immunofluorescence detected immunoglobulin (Ig) M on day 1 and IgG on day 2 for some patients, and in all patients from day 5 onward. Soon after onset of symptoms, patients had IgG and IgM and high viral loads (some >10(9) copies/mL plasma). These data will help healthcare providers select diagnostic tests for returning travelers.


title: Cholesteryl Pullulan Encapsulated TNF-α Nanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus

text: We encapsulated tumor necrosis factor-α (TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG(1) as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.


title: Exacerbated Pathology of Viral Encephalitis in Mice with Central Nervous System-Specific Autoantibodies

text: We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler’s encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C′-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.