title: Clinical characteristics and outcome of ICU admitted MERS corona virus infected patients

text: Abstract Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness. Aim of the work This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection. Patients and methods This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99±13.03years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects. Results The main symptoms among the included patients were: fever (96.87%), cough (93.75%), dyspnea (90.62%), sore throat (75%), runny nose (75%), sputum (50%), headache (43.75%), myalgia (40.62%), chest pain (37.50%), hemoptysis (37.50%), nausea and vomiting (34.37%), abdominal pain (21.87%) and diarrhea (15.62%). The presence of abdominal symptoms is significantly (P <0.05) associated with bad prognosis. Out of the included 32 patients, 18 patients (56.25%) survived and 14 patients (43.75%) expired. There was a statistically significant difference in the duration of symptoms before hospitalization, mechanical ventilation and ICU and total hospital stay between the expired group and survivors (P <0.01). Current smoking and smoking severity were statistically significantly (P <0.01) higher in the expired group compared to survivors. Also, there was a statistically (P <0.05) significant positive correlation between mortality and smoking severity (r =0.640). Most of the expired patients presented with bilateral pulmonary infiltrates or unilateral infiltrates, but most of the survivors presented with normal radiology or increased bronchovascular markings, and this difference in the results was statistically highly significant (P <0.01). There were statistically highly significant (P <0.01) differences in the mean values of APACHE II score (21.11±3.70 vs 24.21±3.82), SOFA score (5.83±2.64 vs 8.85±2.17) and CPIS (7.55±1.14 vs 8.64±1.39) between the expired group and survivors respectively. Also, there was a statistically significant decrease in PH, PaO2, O2 saturation and HCO3 (P <0.05) among the expired group in comparison with the survivors, but no statistical difference regarding PaCO2 (P >0.05). There was a statistically significant positive correlation between mortality and old age (r =0.633), obesity (r =0.712), diabetes mellitus (r =0.685), renal failure (r =0.705), chronic heart diseases (0.591), COPD (r =0.523), malignancy (r =0.692), kidney transplantation (r =0.644) and liver cirrhosis (r =0.525) (P <0.05). There was a statistically (P <0.05) positive correlation between the number of associated co-morbidities and mortality (r =0.735). Conclusions Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients’ hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.


title: Persistent Humoral Immune Responses in the CNS Limit Recovery of Reactivated Murine Cytomegalovirus

text: BACKGROUND: Experimental infection of the mouse brain with murine CMV (MCMV) elicits neuroimmune responses that terminate acute infection while simultaneously preventing extensive bystander damage. Previous studies have determined that CD8(+) T lymphocytes are required to restrict acute, productive MCMV infection within the central nervous system (CNS). In this study, we investigated the contribution of humoral immune responses in control of MCMV brain infection. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing our MCMV brain infection model, we investigated B-lymphocyte-lineage cells and assessed their role in controlling the recovery of reactivated virus from latently infected brain tissue. Brain infiltrating leukocytes were first phenotyped using markers indicative of B-lymphocytes and plasma cells. Results obtained during these studies showed a steady increase in the recruitment of B-lymphocyte-lineage cells into the brain throughout the time-course of viral infection. Further, MCMV-specific antibody secreting cells (ASC) were detected within the infiltrating leukocyte population using an ELISPOT assay. Immunohistochemical studies of brain sections revealed co-localization of CD138(+) cells with either IgG or IgM. Additional immunohistochemical staining for MCMV early antigen 1 (E1, m112–113), a reported marker of viral latency in neurons, confirmed its expression in the brain during latent infection. Finally, using B-cell deficient (Jh(−/−)) mice we demonstrated that B-lymphocytes control recovery of reactivated virus from latently-infected brain tissue. A significantly higher rate of reactivated virus was recovered from the brains of Jh(−/−) mice when compared to Wt animals. CONCLUSION: Taken together, these results demonstrate that MCMV infection triggers accumulation and persistence of B-lymphocyte-lineage cells within the brain, which produce antibodies and play a significant role in controlling reactivated virus.


Migraine in the Time of COVID‐19


title: Advanced Pulmonary and Cardiac Support of COVID-19 Patients: Emerging Recommendations From ASAIO—A “Living Working Document”

text: The severe acute respiratory syndrome (SARS)-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 (COVID)-19 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of COVID-19; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from ASAIO. Of note, this is a “living document,” which will be updated periodically, as additional information and understanding emerges.


title: Coronavirus disease‐2019 in pregnancy with neurological manifestations versus pregnancy with eclampsia: Need for liberal testing to rule out the masquerades

text: We read with interest, the article by Gidlöf et al on the management of a twin pregnancy with severe preeclampsia and Coronavirus disease-2019 (Covid-19) and their call for more liberal testing guidelines in women with high-risk pregnancies, and agree with their suggestion. A severe complication of preeclampsia is eclampsia. Presentations include neurological manifestations such as headache, seizures, loss of consciousness, along with raised blood pressure.


title: Diabetes and COVID‐19: psychosocial consequences of the COVID‐19 pandemic in people with diabetes in Denmark—what characterizes people with high levels of COVID‐19‐related worries?

text: AIM: To map COVID‐19‐specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID‐19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID‐19 pandemic. METHODS: A cross‐sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID‐19‐specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes‐specific social support, diabetes distress and changes in diabetes‐specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID‐19‐specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID‐19, about one‐third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID‐19 and diabetes. CONCLUSION: People with diabetes have COVID‐19‐specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID‐19 and diabetes.


title: Digital work and organisational transformation: Emergent digital/human work configurations in modern organisations

text: Abstract Workplace technologies are more central to working in organisations than ever before. These technologies began as instrumental aids to support office work of individuals but have since also become the basis for social interactions and community building in organisations and more recently become able to perform managerial roles with the use of advanced AI capabilities. Our call for papers to this special issue invited original studies to go further and advance our thinking on the strategic implications of this layered evolution of workplace technologies on work and the structure of organisations. In this introduction, we synthesise the main themes from the special issue, and also ongoing dialogues with the growing community at the regular AIS / IFIP 9.1 workshop on the Changing Nature of Work. A key observation is that the work involved in configuring emergent Digital/Human configurations, is vastly under-reported and poorly understood. Paradoxically, this configuring work is the most demanding and critical in the shaping of modern organisations. We suggest that this type of largely invisible work requires engagement beyond the level of execution or even the meaning of work, it requires intervening with third order effects that get to the core of what an organisation is. We highlight the challenges for organisations in dealing with third order change, particularly because these effects are beyond existing frames of reference and require more dynamic and supple responses based on the values, purpose andintent dominantin the organisation – we describe this as structural digital work. Leaders that are unable or unwilling to engage with effects at this level, and this type of work, will miss identifying core opportunities and risks associated with digital transformation emerging in organisations. We also reflect on the value of current theories and methods used to research this important and emergent phenomenon.


title: Detection of porcine circovirus genotypes 2a and 2b in aborted foetuses from infected swine herds in the State of São Paulo, Brazil

text: BACKGROUND: Porcine circovirus type 2 (PCV2) has been associated with several disease complexes, including reproductive failure. The aim of this study was to identify the subtypes of PCV2 that are associated with reproductive failure in pigs from the State of São Paulo, Brazil and to investigate co-infections with other infectious organisms. FINDINGS: Samples of 168 aborted foetuses or mummified foetuses from five farrow-to-finish swine farms known to be infected with PCV2 and located in the State of São Paulo were tested for PCV2 by polymerase chain reaction (PCR). Positive samples were additionally tested for porcine parvovirus (PPV), Leptospira spp. and Brucella spp. by PCR. PCV2 was detected in 18 of the samples (10.7%). PPV, Brucella spp. and Leptospira spp were found in 2, 10 and 0 cases, respectively. Eleven PCV2 strains were sequenced and determined to be either genotype 2a (n = 1) or 2b (n = 10). CONCLUSIONS: The findings indicate that the frequency of PCV2 infections in aborted porcine foetuses from the State of São Paulo is rather low (10.7%) and that co-infection with other pathogens is common and may be involved in PCV2 associated reproductive failure. No repeatable, characteristic amino acid motifs for regions of the PCV2 capsid protein seemed to be associated with abortion in sows.


title: MicroRNA-155 enhances T cell trafficking and antiviral effector function in a model of coronavirus-induced neurologic disease

text: BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that modulate cellular gene expression, primarily at the post-transcriptional level. We sought to examine the functional role of miR-155 in a model of viral-induced neuroinflammation. METHODS: Acute encephalomyelitis and immune-mediated demyelination were induced by intracranial injection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) into C57BL/6 miR-155(+/+) wildtype (WT) mice or miR-155(−/−) mice. Morbidity and mortality, viral load and immune cell accumulation in the CNS, and spinal cord demyelination were assessed at defined points post-infection. T cells harvested from infected mice were used to examine cytolytic activity, cytokine activity, and expression of certain chemokine receptors. To determine the impact of miR-155 on trafficking, T cells from infected WT or miR-155(−/−) mice were adoptively transferred into RAG1(−/−) mice, and T cell accumulation into the CNS was assessed using flow cytometry. Statistical significance was determined using the Mantel-Cox log-rank test or Student’s T tests. RESULTS: Compared to WT mice, JHMV-infected miR-155(−/−) mice developed exacerbated disease concomitant with increased morbidity/mortality and an inability to control viral replication within the CNS. In corroboration with increased susceptibility to disease, miR-155(−/−) mice had diminished CD8(+) T cell responses in terms of numbers, cytolytic activity, IFN-γ secretion, and homing to the CNS that corresponded with reduced expression of the chemokine receptor CXCR3. Both IFN-γ secretion and trafficking were impaired in miR-155(−/−), virus-specific CD4(+) T cells; however, expression of the chemokine homing receptors analyzed on CD4(+) cells was not affected. Except for very early during infection, there were not significant differences in macrophage infiltration into the CNS between WT and miR-155(−/−) JHMV-infected mice, and the severity of demyelination was similar at 14 days p.i. between WT and miR-155(−/−) JHMV-infected mice. CONCLUSIONS: These findings support a novel role for miR-155 in host defense in a model of viral-induced encephalomyelitis. Specifically, miR-155 enhances antiviral T cell responses including cytokine secretion, cytolytic activity, and homing to the CNS in response to viral infection. Further, miR-155 can play either a host-protective or host-damaging role during neuroinflammation depending on the disease trigger.


title: Screening of Feral and Wood Pigeons for Viruses Harbouring a Conserved Mobile Viral Element: Characterization of Novel Astroviruses and Picornaviruses

text: A highly conserved RNA-motif of yet unknown function, called stem-loop-2-like motif (s2m), has been identified in the 3′ end of the genomes of viruses belonging to different RNA virus families which infect a broad range of mammal and bird species, including Astroviridae, Picornaviridae, Coronaviridae and Caliciviridae. Since s2m is such an extremely conserved motif, it is an ideal target for screening for viruses harbouring it. In this study, we have detected and characterized novel viruses harbouring this motif in pigeons by using a s2m-specific amplification. 84% and 67% of the samples from feral pigeons and wood pigeons, respectively, were found to contain a virus harbouring s2m. Four novel viruses were identified and characterized. Two of the new viruses belong to the genus Avastrovirus in the Astroviridae family. We propose two novel species to be included in this genus, Feral pigeon astrovirus and Wood pigeon astrovirus. Two other novel viruses, Pigeon picornavirus A and Pigeon picornavirus B, belong to the Picornaviridae family, presumably to the genus Sapelovirus. Both of the novel picornaviruses harboured two adjacent s2m, called (s2m)(2), suggesting a possible increased functional effect of s2m when present in two copies.


Clinical course of patients infected with SARS-CoV-2 soon after thoracoscopic lung surgery


title: Male preponderance of COVID‐19 risk

text: In this editorial, Roger Kirby, Editor‐in‐Chief on Trends in Urology and Men's Health, discusses the discusses the male preponderance of the COVID‐19 mortality risk.


title: How do we recover from COVID‐19? Helping diabetes teams foresee and prepare for the psychological harms

text: The scale of the COVID‐19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large‐scale disasters indicates that following a first wave of admissions and deaths from COVID‐19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long‐term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second‐ and third‐wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.


title: Cardiological society of India position statement on COVID-19 and heart failure

text: The COVID 19 global pandemic has engulfed humanity with a huge impact on health systems across the world. Many patients develop myocardial injury which can lead to significant cardiovascular complications including HF. This will require aggressive management strategies which are evolving. Guideline directed drug therapy including ACEI/ARB/ARNI is to be continued in patients with pre-existing HF. Long-term cardiovascular effects of COVID-19 are yet to be ascertained. Protection of health care personnel from contracting the disease should be given high priority.


title: Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan’s Experience

text: The COVID-19 outbreak has led to 80,409 diagnosed cases and 3,012 deaths in mainland China based on the data released on March 4, 2020. Approximately 3.2% of patients with COVID-19 required intubation and invasive ventilation at some point in the disease course. Providing best practices regarding intubation and ventilation for an overwhelming number of patients with COVID-19 amid an enhanced risk of cross-infection is a daunting undertaking. The authors presented the experience of caring for the critically ill patients with COVID-19 in Wuhan. It is extremely important to follow strict self-protection precautions. Timely, but not premature, intubation is crucial to counter a progressively enlarging oxygen debt despite high-flow oxygen therapy and bilevel positive airway pressure ventilation. Thorough preparation, satisfactory preoxygenation, modified rapid sequence induction, and rapid intubation using a video laryngoscope are widely used intubation strategies in Wuhan. Lung-protective ventilation, prone position ventilation, and adequate sedation and analgesia are essential components of ventilation management.


title: Genomic Sequences of two Novel Levivirus Single-Stranded RNA Coliphages (Family Leviviridae): Evidence for Recombinationin Environmental Strains

text: Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal waters 1130 km apart (North Carolina and Rhode Island, USA), these strains shared 97% nucleotide similarity and 97–100% amino acid similarity. When the novel strains were compared to nine Levivirus genogroup I strains, they shared 95–100% similarity among the maturation, capsid and lysis proteins, but only 84–85% in the RNA-dependent RNA polymerase gene. Further bioinformatic analyses suggested a recombination event occurred. To the best of our knowledge, this is the first description of viral recombinants in environmental Leviviridae ssRNA bacteriophages.


title: Community's compliance with measures for the prevention of respiratory infections in Riyadh, Saudi Arabia

text: BACKGROUND: Acute respiratory tract infections are the most common causes of both morbidity and mortality worldwid, and the management and prevention of acute respiratory infections is a global problem, especially in developing countries. This study sought to assess the community's compliance and practice of measures for the prevention of respiratory infections and discover their source of health information. MATERIALS AND METHODS: A cross-sectional study was carried out in the five biggest shopping malls in Riyadh city in July 2014. The required sample size was 980 persons aged 15 or older, with 196 from each of the five biggest shopping malls from each of the five geographic areas of Riyadh. Data was collected by face-to-face interview using standardised questionnaire, and analyzed using SPSS. RESULTS: Overall, 48.3% of the participants thought that they were susceptible to any of the respiratory infections of pandemic influenza; 59.7% always washed their hands with water and soap and 34.8% used antibacterial soap. About 29% reported avoiding touching their eyes, noses, and mouths directly with their hands; 63.5% covered their noses and mouths with tissue paper when sneezing or coughing. A substantial number said they “never” shared their personal stuff, including towels (70.5%) and utensils (49.0%) with others. Only 21.2% avoided crowded places or wore a mask (9.1%) in such a situation. A high proportion (62.8%) did not take the seasonal flu vaccine. The most common sources of health information included television/radio (47.9%), social media (29.4%), and friends/family (28.1%). CONCLUSIONS: Health authorities should seize every opportunity to prevent respiratory infections by adopting all evidence-based infection control measures to improve public awareness, attitude, and practice.


Recommandations de la Société Française de Médecine du Travail (SFMT) : Avis relatif à l’affectation, dans le contexte de l’épidémie SARS-CoV-2 (Covid-19), des professionnels exerçant en milieu de soins et travailleurs assimilés, présentant une pathologie chronique traitée par anti-inflammatoires no


title: El SRAA y el SARS-CoV-2: el acertijo a resolver

text: Resumen El 31 de diciembre de 2019 se reportó el primer caso de COVID-19 en Wuhan, China, y desde entonces ha habido un interés creciente y sin precedentes por conocer todos los aspectos vinculados con esta nueva enfermedad. Uno de los temas que ha generado debate se vincula con la asociación entre la terapia antihipertensiva con inhibidores del sistema renina-angiotensina-aldosterona (SRAA) y la infección por el virus SARS-CoV-2. Si bien muchas preguntas siguen hoy día sin poder ser respondidas, la intención de este comunicado es informar a los profesionales de la salud acerca del estado actual de conocimiento. Dado que este es un tema en constante evolución, se recomienda su actualización a medida que se presenten nuevas evidencias. A continuación, daremos revisión a los estudios preclínicos y clínicos que relacionan el coronavirus con el SRAA. Abstract The first case of COVID-19 was reported on 31 December 2019 in Wuhan, China. Ever since there has been unprecedented and growing interest in learning about all aspects of this new disease. Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection. While many questions as yet remain unanswered, the aim of this report is to inform health professionals about the current state of knowledge. Because this is an ever-evolving topic, the recommendation is that it be updated as new evidence becomes available. Below, we provide a review of pre-clinical and clinical studies that link coronavirus to the RAAS.


title: Point-of-Care Diagnostic Services as an Integral Part of Health Services during the Novel Coronavirus 2019 Era

text: Point-of-care (POC) diagnostic services are commonly associated with pathology laboratory services This issue presents a holistic approach to POC diagnostics services from a variety of disciplines including pathology, radiological and information technology as well as mobile technology and artificial intelligence This highlights the need for transdisciplinary collaboration to ensure the efficient development and implementation of point-of-care diagnostics The advent of the novel coronavirus 2019 (COVID-19) pandemic has prompted rapid advances in the development of new POC diagnostics Global private and public sector agencies have significantly increased their investment in the development of POC diagnostics There is no longer a question about the availability and accessibility of POC diagnostics The question is "how can POC diagnostic services be integrated into health services in way that is useful and acceptable in the COVID-19 era?"


Chronic cutaneous ulcers management in dermatologic department during COVID‐19 era


How to “Detronize” Virus in Crown – Questions to Current Stem Cell Therapies


docid: bxdpdjlc

title: RETRACTED: Autoadaptive ER-Associated Degradation Defines a Preemptive Unfolded Protein Response Pathway

text: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors. The study reported that expression of misfolded proteins in the ER affects the composition and stability of the dislocation machinery built around the HRD1 E3 ubiquitin ligase in the absence of UPR induction. During efforts to extend this work, the authors have been unable to replicate some of the results obtained by the first author of the paper, which describe the mechanisms regulating the rapid turnover of HERP and how the presence of misfolded proteins affects the composition and the stability of the HRD1 complex. The authors therefore wish to immediately retract the paper. The authors’ lab continues working on the regulation of the ERAD machinery aiming to publish verified data in t52/6he near future. The authors sincerely apologize for any difficulties that may have been experienced by the scientific community. The first author, R.B., declined to sign the retraction notice.


title: Nurses' Working Conditions: Implications for Infectious Disease

text: Poor working conditions are associated with risk for occupational infections.


title: Detection of coronavirus RNA and antigen in multiple sclerosis brain

text: Epidemiological studies of patients with multiple sclerosis (MS) and animal model data support the hypothesis that viruses initiate the immunopathogenic events leading to demyelination in MS. There have been no reports, however, of consistent detection of viruses in MS central nervous system tissue. We probed MS and control brain with cDNA probes specific for human, murine, porcine, and bovine coronaviruses. We report the in situ hybridization detection of coronavirus RNA in 12 of 22 MS brain samples using cloned coronavirus cDNA probes. In addition, tissue was screened for coronavirus antigen by immunohistochemical methods; antigen was detected in two patients with rapidly progressive MS. Significant amounts of coronavirus antigen and RNA were observed in active demyelinating plaques from these two patients. These findings show that coronaviruses can infect the human central nervous system and raise the possibility that these viruses may contribute to the pathogenesis of MS in some patients.


docid: auvtwmcq

title: Giardiosis and other enteropathogenic infections: a study on diarrhoeic calves in Southern Germany

text: BACKGROUND: Diarrhoea induces massive problems in the rearing of calves. The aim of the study was to obtain current data about the frequency of Giardia spp., Cryptosporidium spp. and Eimeria spp. in diarrhoeic calves in Southern Germany with the particular focus on giardiosis. RESULTS: 1564 samples were analysed for the three pathogens using microscopical methods. Giardia spp. was detectable in 112/1564 samples (7.2%). The mean age was 46.5 days and the odds of being infected with Giardia spp. increased slowly up to 8 times from about 12 days to 30 days of age. There appeared to be no seasonal influence on the frequency of Giardia spp. A mono-infection with Giardia spp. was diagnosed in 46 calves (2.9%) whereas 15 calves (1.0%) had a mixed-infection with Cryptosporidium spp. and 51 calves (3.3%) with Eimeria spp. Cryptosporidium spp. and Eimeria spp. could be detected in 646/1564 samples (41.3%) and 208/1564 samples (13.3%), respectively, with a mean age of 11.3 and 55.0 days, respectively. The odds of being infected with Cryptosporidium spp. increased up to 4.5 times until an age of 10 days. After that the odds decreased continuously and was approaching zero at about 30 days. The odds of being infected with Eimeria spp. increased continuously up to 30 times from about 20 days to 60 days of age. There appeared to be no significant seasonal influence on the frequency of Cryptosporidium spp.; but there was one for Eimeria spp.: the odds of being infected with Eimeria spp. in March and April decreased by about half and increased up to 2.3 times between July and September. Additionally, as requested by the veterinarians, 1282 of those samples were analysed for E. coli, Rota-, Coronavirus and Cryptosporidium spp. using an ELISA. Obtained frequencies for these pathogens were 0.9%, 37.8%, 3.4% and 45.3% with a mean age of 24.8 days, 12.1 days, 9.0 days and 12.1 days, respectively. CONCLUSIONS: The results indicate that in Southern Germany in addition to Eimeria spp., Giardia spp. seems to play a contributing role in diarrhoea in older calves, whereas Cryptosporidium spp. and Rotavirus are mostly relevant in young calves.


La Società Italiana di Endocrinologia (SIE) e l’epidemia COVID-19


title: Innovation During COVID-19: Improving Addiction Treatment Access

text: During the COVID-19 pandemic, many addiction treatment and harm reduction organizations have had to reduce their hours and services for people with substance use disorders, placing these individuals at increased risk of death. In order to address restricted treatment access during COVID-19, guidance from the Substance Abuse Mental Health Services Administration, the US Drug Enforcement Administration, and the US Department of Health and Human Services has allowed for use of audio-only telehealth encounters for buprenorphine induction without requiring an in-person evaluation or video interface. This has enabled innovations in order to try to meet the needs of the most vulnerable among us during the current pandemic. In this new regulatory environment, we established the Rhode Island Buprenorphine Hotline, a phone hotline which functions as a “tele-bridge” clinic where people with moderate to severe opioid use disorder can be linked with a DATA 2000 waivered provider who can provide an initial assessment and, if appropriate, prescribe buprenorphine for unobserved induction and linkage to outpatient treatment. In this correspondence we briefly share our experience developing this common sense approach to addressing the complex problem of access to treatment only now permissible due to regulatory changes during COVID-19.


title: Managing Cardiac Implantable Electronic Device Patients during a Health Care Crisis: Practical Guidance

text: Abstract Our world is faced with a global pandemic that threatens to overwhelm many national health care systems for a prolonged period. Consequently, the elective long-term CIED management of millions of patients is potentially compromised raising the likelihood of patients experiencing major adverse events due to loss of CIED therapy. This review gives practical guidance to health care providers to help promptly recognize the requirement for expert consultation for urgent interrogation and/or surgery in CIED patients.


title: A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene

text: Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to comprehensively and systematically analyze the SNPs of MBL2 gene. The present study was carried out to identify and prioritize the SNPs of MBL2 gene for further genotyping and functional studies. To predict the possible impact of SNPs on MBL structure and function SNP data obtained from dbSNP database were analyzed using various bioinformatics tools. Out of total 661 SNPs, only 37 validated SNPs having minor allele frequency ≥0.10 were considered for the present study. These 37 SNPs includes one in 3′ near gene, nine in 3′ UTR, one non-synonymous SNP (nsSNP), thirteen intronic SNPs and thirteen in 5′ near gene. From these 37 SNPs, 11 non-coding SNPs were identified to be of functional significance and evolutionary conserved. Out of these, 4 SNPs from 3′ UTR were found to play role in miRNA binding, 7 SNPs from 5′ near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. Protein structural analysis with this amino acid variant was performed by using I-TASSER, RAMPAGE, Swiss-PdbViewer, Chimera and I-mutant. Information regarding solvent accessibility, molecular dynamics and energy minimization calculations showed that this variant causes clashes with neighboring amino acids residues that must interfere in the normal triple helix formation of trimeric subunit and further with the normal assembly of MBL oligomeric form, hence decrease in stability. Thus, findings of the present study indicated 12 SNPs of MBL2 gene to be functionally important. Exploration of these variants may provide novel remedial markers for various diseases.


title: Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital, China

text: Based on the New Diagnosis and Treatment Scheme for Novel Coronavirus Infected Pneumonia (Trial Edition 5), combined with our current clinical treatment experience, we recently proposed a revision of the first edition of “Guidance for maternal and fetal management during pneumonia epidemics of novel coronavirus infection in the Wuhan Tongji Hospital”. This article focused on the issues of greatest concern of pregnant women including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnostic criteria, inspection precautions, drug treatment options, indications and methods of termination of pregnancy, postpartum fever, breastfeeding considerations, mode of mother-to-child transmission, neonatal isolation and advice on neonatal nursing, to provide valuable experience for better management of SARS-CoV-2 infection in pregnant women and newborns.


docid: gntfsqtd

title: Tourism expansion and economic development: The case of Taiwan

text: This study examines the causal relationship between tourism expansion and economic development in Taiwan. A Granger causality test is performed following the cointegration approach to reveal the direction of causality between economic growth and tourism expansion. Test results indicate a long-run equilibrium relationship and further a bi-directional causality between the two factors. In other words, in Taiwan, tourism and economic development reinforce each other. A discussion follows and managerial implications are identified based on the empirical findings.


title: Infection of SARS-CoV on juvenile and adult Brandt’s voleMicrotus brandtii

text: We studied the infectious effect of SARS-CoV virus on juvenile and adult Brandt’s Vole (Microtus brandtii) by nasal cavity spraying method (CCID(50) is 10(5.7)). SARS virus caused serious deaths in adults. The death adults demonstrated hemorrhage from mouth, nasal cavity and intestine, hemorrhageious interstitial pneumonia and gore in liver, spleen and kidney. The survival adults demonstrated local hemorrhagic spot in lung and emphysema, but the other organs showed no pathological abnormality. SARS virus caused no deaths in juveniles, but locomotion of infected juveniles became slower. In the early stage, there was local pneumonia in lung and SARS viruses were isolated from the pathological tissue. Only one control juvenile lived and the infected juvenile showed local pneumonia in lung. The results demonstrated that SARS-CoV infected Brandt’s vole seriously and adults were more susceptive to SARS-CoV than juveniles. The Brandt’s vole may be a potential animal model for SARS research.


title: Empower Women in Healthcare to move Women’s Health forward

text: Abstract Medical science and patient care have historically focused on male patients. Many diagnoses in women are still undetermined and it takes several years longer to establish comparable diagnoses in women as in men. Women live longer and have more unhealthy years with ageing than men. Sociocultural aspects vary importantly between the genders and have a different impact on health, wellbeing and many diseases. We still have a long way to go to achieve gender equality and equal rights for women worldwide. Female values, such as creativity, empathy, mutual connection and emotional skills, are eminent in healthcare. Efforts to establish more highly respected and leading positions for women working in the health sector will be a great incentive to put women’s health higher on the agenda.


Risk factors and dynamics of household transmission of respiratory syncytial virus and other respiratory viruses in rural Nepal


title: Potent and selective inhibition of pathogenic viruses by engineered ubiquitin variants

text: The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses. A variety of viral DUBs (vDUBs), including the MERS-CoV papain-like protease, are responsible for cleaving the viral replicase polyproteins during replication, and are thereby critical components of the viral replication cycle. Together, this makes vDUBs highly attractive antiviral drug targets. However, structural similarity between the catalytic cores of vDUBs and human DUBs complicates the development of selective small molecule vDUB inhibitors. We have thus developed an alternative strategy to target the vDUB activity through a rational protein design approach. Here, we report the use of phage-displayed ubiquitin variant (UbV) libraries to rapidly identify potent and highly selective protein-based inhibitors targeting the DUB domains of MERS-CoV and CCHFV. UbVs bound the vDUBs with high affinity and specificity to inhibit deubiquitination, deISGylation and in the case of MERS-CoV also viral replicative polyprotein processing. Co-crystallization studies further revealed critical molecular interactions between UbVs and MERS-CoV or CCHFV vDUBs, accounting for the observed binding specificity and high affinity. Finally, expression of UbVs during MERS-CoV infection reduced infectious progeny titers by more than four orders of magnitude, demonstrating the remarkable potency of UbVs as antiviral agents. Our results thereby establish a strategy to produce protein-based inhibitors that could protect against a diverse range of viruses by providing UbVs via mRNA or protein delivery technologies or through transgenic techniques.


title: Circulation of pantropic canine coronavirus in autochthonous and imported dogs, Italy

text: Canine coronavirus (CCoV) strains with the ability to spread to internal organs, also known as pantropic CCoVs (pCCoVs), have been detected in domestic dogs and wild carnivores. Our study focused on the detection and molecular characterization of pCCoV strains circulating in Italy during the period 2014–2017 in autochthonous dogs, in dogs imported from eastern Europe or illegally imported from an unknown country. Samples from the gut and internal organs of 352 dogs were screened for CCoV; putative pCCoV strains, belonging to subtype CCoV‐IIa, were identified in the internal organs of 35 of the examined dogs. Fifteen pCCoV strains were subjected to sequence and phylogenetic analyses, showing that three strains (98960‐1/2016, 98960‐3/2016, 98960‐4/2016) did not cluster either with Italian or European CCoVs, being more closely related to alphacoronaviruses circulating in Asia with which they displayed a 94%–96% nucleotide identity in partial spike protein gene sequences. The pCCoV‐positive samples were also tested for other canine viruses, showing co‐infections mainly with canine parvovirus.


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title: What works and what does not work in response to COVID-19 prevention and control in Africa

text: Abstract Since the emergence of the pandemic in December 2019 in Wuhan, China, as of 10:00 CEST, June 6, 2020, there have been nearly 6,663,304 confirmed cases of COVID-19 including 392,802 deaths worldwide. In Africa, as of June 2, 2020, a total of 152,442 COVID-19 cases and 4334 deaths have been reported. The five countries with the highest commutative number of cases in Africa are South Africa, Egypt, Nigeria, Algeria, and Ghana. Africa, together with the rest of world have had to swiftly undertake measures necessary to protect the continent from irreversible effects of the COVID-19 pandemic that is claiming lives and destroying livelihoods. The lower number of COVID-19 cases in most African countries is attributed to inadequate health systems, low-to-absent testing capacity, poor reporting system and insufficient number of medical staff. The COVID-19 pandemic poses a great threat to most African countries from cities to rural areas and has created a strong demand on already scarce resources and requires an intense mobilization of additional resources to implement established emergency contingency measures. Closure of borders and movements of people restrictions within the country as measures to prevent the spread of COVID-19; this has resulted in the sector being adversely affected by the loss of income. Cooperative prevention and control measures are one of the promising solutions to deplete the spread of COVID-19 on the continent.


title: Detection of Severe Acute Respiratory Syndrome Coronavirus in the Brain: Potential Role of the Chemokine Mig in Pathogenesis

text: Background. Previous studies have shown that common human coronavirus might be neurotropic, although it was first isolated as a pathogen of the respiratory tract. We noticed that a few patients with severe acute respiratory syndrome (SARS) experienced central nervous symptoms during the course of illness. In the present study, we isolated a SARS coronavirus strain from a brain tissue specimen obtained from a patient with SARS with significant central nervous symptoms. Methods. Using transmission electronic microscopy and nested reverse transcription–polymerase chain reaction, the causative pathogen was identified in cultures of a brain tissue specimen obtained from the patient with SARS. Histopathologic examination of the brain tissue was performed using the methods of immunohistochemistry analysis and double immunofluorescence staining. Fifteen cytokines and chemokines were detected in the blood of the patient with SARS by means of a bead-based multiassay system. Results. A fragment specific for SARS human coronavirus was amplified from cultures of the brain suspension, and transmission electronic microscopy revealed the presence of an enveloped virus morphologically compatible with a coronavirus isolated in the cultures. Pathologic examination of the brain tissue revealed necrosis of neuron cells and broad hyperplasia of gliocytes. Immunostaining demonstrated that monokine induced by interferon-Γ (Mig) was expressed in gliocytes with the infiltration of CD68(+) monocytes/macrophages and CD3(+) T lymphocytes in the brain mesenchyme. Cytokine/chemokine assay revealed that levels of interferon-Γ–inducible protein 10 and Mig in the blood were highly elevated, although the levels of other cytokines and chemokines were close to normal. Conclusions. This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.


title: Interfering antiviral immunity: application, subversion, hope?

text: RNA interference (RNAi), initially recognized as a natural antiviral mechanism in plants, has rapidly emerged as an invaluable tool to suppress gene expression in a sequence-specific manner in all organisms, including mammals. Its potential to inhibit the replication of a variety of viruses has been demonstrated in vitro and in vivo in mouse and monkey models. These results have generated profound interest in the use of this technology as a potential treatment strategy for viral infections for which vaccines and drugs are unavailable or inadequate. In this review, we discuss the progress made within the past 2–3 years towards harnessing the potential of RNAi for clinical application in viral infections and the hurdles that have yet to be overcome.


title: Optimal media reporting intensity on mitigating spread of an emerging infectious disease

text: Mass media reports can induce individual behaviour change during a disease outbreak, which has been found to be useful as it reduces the force of infection. We propose a compartmental model by including a new compartment of the intensity of the media reports, which extends existing models by considering a novel media function, which is dependent both on the number of infected individuals and on the intensity of mass media. The existence and stability of the equilibria are analyzed and an optimal control problem of minimizing the total number of cases and total cost is considered, using reduction or enhancement in the media reporting rate as the control. With the help of Pontryagin’s Maximum Principle, we obtain the optimal media reporting intensity. Through parameterization of the model with the 2009 A/H1N1 influenza outbreak data in the 8th Hospital of Xi’an in Shaanxi Province of China, we obtain the basic reproduction number for the formulated model with two particular media functions. The optimal media reporting intensity obtained here indicates that during the early stage of an epidemic we should quickly enhance media reporting intensity, and keep it at a maximum level until it can finally weaken when epidemic cases have decreased significantly. Numerical simulations show that media impact reduces the number of cases during an epidemic, but that the number of cases is further mitigated under the optimal reporting intensity. Sensitivity analysis implies that the outbreak severity is more sensitive to the weight α(1) (weight of media effect sensitive to infected individuals) than weight α(2) (weight of media effect sensitive to media items).


title: Antiviral therapies targeting host ER alpha-glucosidases: Current status and future directions

text: Abstract Endoplasmic reticulum (ER)-resident α-glucosidases I and II sequentially trim the three terminal glucose moieties on N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because most viral envelope glycoproteins contain N-linked glycans, inhibition of ER α-glucosidases with derivatives of 1-deoxynojirimycin (DNJ) or castanospermine (CAST), two well-studied pharmacophores of α-glucosidase inhibitors, efficiently disrupts the morphogenesis of a broad spectrum of enveloped viruses. Moreover, both DNJ and CAST derivatives have been demonstrated to prevent the death of mice infected with several distinct flaviviruses and filoviruses and suppress the multiplication of several other species of viruses in infected animals. N-Butyl derivative of DNJ (NB-DNJ) and 6 O-bytanoyl prodrug of CAST (Bu-CAST) have been evaluated in human clinical trials for their antiviral activities against human immunodeficiency virus and hepatitis C virus, and there is an ongoing trial of treating dengue patients with Bu-CAST. This article summarizes the current status of ER α-glucosidase-targeted antiviral therapy and proposes strategies for development of more efficacious and specific ER α-glucosidase inhibitors as broad-spectrum, drug resistance-refractory antiviral therapeutics. These host function-targeted, broad-spectrum antiviral agents do not rely on time-consuming etiologic diagnosis, and should therefore be particularly promising in the management of viral hemorrhagic fever and respiratory tract viral infections, medical conditions that can be caused by many different enveloped RNA viruses, with a short window for medical intervention.


title: Health Care Worker Contact with MERS Patient, Saudi Arabia

text: To investigate potential transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) to health care workers in a hospital, we serologically tested hospital contacts of the index case-patient in Saudi Arabia, 4 months after his death. None of the 48 contacts showed evidence of MERS-CoV infection.


title: Moving towards a new vision: implementation of a public health policy intervention

text: BACKGROUND: Public health systems in Canada have undergone significant policy renewal over the last decade in response to threats to the public’s health, such as severe acute respiratory syndrome. There is limited research on how public health policies have been implemented or what has influenced their implementation. This paper explores policy implementation in two exemplar public health programs -chronic disease prevention and sexually-transmitted infection prevention - in Ontario, Canada. It examines public health service providers’, managers’ and senior managements’ perspectives on the process of implementation of the Ontario Public Health Standards 2008 and factors influencing implementation. METHODS: Public health staff from six health units representing rural, remote, large and small urban settings were included. We conducted 21 focus groups and 18 interviews between 2010 (manager and staff focus groups) and 2011 (senior management interviews) involving 133 participants. Research assistants coded transcripts and researchers reviewed these; the research team discussed and resolved discrepancies. To facilitate a breadth of perspectives, several team members helped interpret the findings. An integrated knowledge translation approach was used, reflected by the inclusion of academics as well as decision-makers on the team and as co-authors. RESULTS: Front line service providers often were unaware of the new policies but managers and senior management incorporated them in operational and program planning. Some participants were involved in policy development or provided feedback prior to their launch. Implementation was influenced by many factors that aligned with Greenhalgh and colleagues’ empirically-based Diffusion of Innovations in Service Organizations Framework. Factors and related components that were most clearly linked to the OPHS policy implementation were: attributes of the innovation itself; adoption by individuals; diffusion and dissemination;the outer context – interorganizational networks and collaboration; the inner setting – implementation processes and routinization; and, linkage at the design and implementation stage. CONCLUSIONS: Multiple factors influenced public health policy implementation. Results provide empirical support for components of Greenhalgh et al’s framework and suggest two additional components – the role of external organizational collaborations and partnerships as well as planning processes in influencing implementation. These are important to consider by government and public health organizations when promoting new or revised public health policies as they evolve over time. A successful policy implementation process in Ontario has helped to move public health towards the new vision. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3056-3) contains supplementary material, which is available to authorized users.


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title: Ebola Virus Disease Epidemic: What Can the World Learn and Not Learn from West Africa?

text: With over 4,500 deaths and counting, and new cases identified in two developed countries that are struggling and faltering in their handling of the epidemic, the 2014 Ebola Virus Disease (EVD) epidemic is unlike any of its kind ever encountered. The ability of some poor, resource-limited, developing countries in sub-Saharan Africa to efficiently handle the epidemic within their shores provides some lessons learned for the global health community. Among others, the 2014 EVD epidemic teaches us that it is time to put the “P” back in public and population health around the world. The global health community must support a sustainable strategy to mitigate Ebola virus and other epidemics both within and outside their shores, even after the cameras are gone. Ebola virus must not be called the disease of the poor and developing world.


title: The Perfect Moral Storm: Diverse Ethical Considerations in the COVID-19 Pandemic

text: The COVID-19 pandemic has both exposed and created deep rifts in society. It has thrust us into deep ethical thinking to help justify the difficult decisions many will be called upon to make and to protect from decisions that lack ethical underpinnings. This paper aims to highlight ethical issues in six different areas of life highlighting the enormity of the task we are faced with globally. In the context of COVID-19, we consider health inequity, dilemmas in triage and allocation of scarce resources, ethical issues associated with research, ethical considerations relating to tracing apps, and exit strategies such as immunity passports and COVID-19 vaccines. Finally, we consider environmental issues in light of COVID-19. The paper also offers some ethical reflection on these areas as many parts of the world contemplate the recovery phase.


The Orthopaedic Trauma Service and COVID-19: Practice Considerations to Optimize Outcomes and Limit Exposure


title: COVID-19: Are we dealing with a multisystem vasculopathy in disguise of a viral infection?

text: After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic with unprecedented global response. With the expanding domain of presentations in COVID-19 patients, the full range of manifestations is yet to unfold. The classical clinical symptoms for SARS-CoV-2 affected patients are dry cough, high fever, dyspnoea, lethal pneumonia whereas many patients have also been found to be associated with a few additional signs and clinical manifestations of isolated vasculopathy. Albeit a deep and profound knowledge has been gained on the clinical features and management of COVID-19, less clear association has been provided on SARS-CoV-2 mediated direct or indirect vasculopathy and its possible correlation with disease prognosis. The accumulative evidences suggest that novel coronavirus, apart from its primary respiratory confinement, may also invade vascular endothelial cells of several systems including cerebral, cardio-pulmonary as well as renal microvasculature, modulating multiple visceral perfusion indices. Here we analyse the phylogenetic perspective of SARS-CoV-2 along with other strains of β-coronaviridae from a standpoint of vasculopathic derangements. Based on the existing case reports, literature and open data bases, we also analyse the differential pattern of vasculopathy related changes in COVID-19 positive patients. Besides, we debate the need of modulation in clinical approach from a hemodynamical point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV-2 affected patients.


title: Prenatal and childhood infections: implications for the development and treatment of childhood asthma

text: Summary Bacterial and viral infections occur early and recurrently in life and thereby impose a substantial disease burden. Besides causing clinical symptoms, a potential role of infection in the development of the asthma syndrome later in life has also been suggested. However, whether bacterial and viral infections unmask host factors in children at risk of asthma or whether they directly cause asthma remains unclear; both viewpoints could be justified, but the underlying mechanisms are complex and poorly understood. Recently, the role of the bacterial microbiome has been emphasised. But data are still sparse and future studies are needed for definitive conclusions to be made. In this Review, we discuss present knowledge of viruses and bacteria that infect and colonise the respiratory tract and mucosal surfaces, including their timepoint of action, host factors related to infection, and their effect on childhood asthma. Childhood asthma could be the result of a combination of altered host susceptibility and infectious agents.


title: The challenges of remote working

text: The exhortation to stay at home to comply with the current legal requirement for social distancing has put the delivery of healthcare services in an unusual position The Healthcare Protection (Coronavirus Restrictions) Regulations 2020, resulted in the closure of restaurants and pubs along with the limitation on individuals leaving their homes except for exercise, medical reasons, food shopping and supporting vulnerable neighbours Whilst anyone with a job was encouraged to work from home, key workers are still allowed to travel to their place of work


title: Development of a standard treatment protocol for severe acute respiratory syndrome

text: Summary A series of 31 patients with probable SARS, diagnosed from WHO criteria, were treated according to a treatment protocol consisting of antibacterials and a combination of ribavirin and methylprednisolone. Through experience with the first 11 patients, we were able to finalise standard dose regimens, including pulsed methylprednisolone. One patient recovered on antibacterial treatment alone, 17 showed rapid and sustained responses, and 13 achieved improvement with step-up or pulsed methylprednisolone. Four patients required short periods of non-invasive ventilation. No patient required intubation or mechanical ventilation. There was no mortality or treatment morbidity in this series.


title: SARS in Healthcare Facilities, Toronto and Taiwan

text: The healthcare setting was important in the early spread of severe acute respiratory syndrome (SARS) in both Toronto and Taiwan. Healthcare workers, patients, and visitors were at increased risk for infection. Nonetheless, the ability of individual SARS patients to transmit disease was quite variable. Unrecognized SARS case-patients were a primary source of transmission and early detection and intervention were important to limit spread. Strict adherence to infection control precautions was essential in containing outbreaks. In addition, grouping patients into cohorts and limiting access to SARS patients minimized exposure opportunities. Given the difficulty in implementing several of these measures, controls were frequently adapted to the acuity of SARS care and level of transmission within facilities. Although these conclusions are based only on a retrospective analysis of events, applying the experiences of Toronto and Taiwan to SARS preparedness planning efforts will likely minimize future transmission within healthcare facilities.


title: Insufficient preparedness of primary care practices for pandemic influenza and the effect of a preparedness plan in Japan: a prefecture-wide cross-sectional study

text: BACKGROUND: Cases of emerging infectious diseases, including H5N1 influenza, H7N9 influenza, and Middle East Respiratory Syndrome, have been reported in recent years, and the threat of pandemic outbreaks persists. In Japan, primary care is the frontline against emerging infectious diseases in communities. Although the importance of pandemic preparedness in primary care has been highlighted previously, few studies have thus far investigated the preparedness among primary care practices (PCPs) or differences in the preparedness of different institutional settings. We examined PCP preparedness and response to the 2009 influenza pandemic in Japan, and explored the role of a pandemic preparedness plan during the pandemic. METHODS: We used a survey questionnaire to assess how well individual PCPs in Okinawa, Japan, were prepared for the 2009 influenza pandemic. The questionnaire was mailed to all eligible PCPs (N = 465) in Okinawa, regardless of their institutional setting. In addition, we assessed the differences in the preparedness of clinics and hospitals and determined whether the national preparedness plan affected individual preparedness and response. Data were analyzed using descriptive and logistic regression analyses. RESULTS: A total of 174 (37.4%) PCPs responded to our survey. In general, high-level personal protective equipment (PPE) such as N95 masks (45.4%), gowns (30.5%), and eye protection (21.3%) was stocked at a low rate. Clinic-based PCPs were significantly less prepared than hospital-based PCPs to provide N95 masks (OR 0.34), gowns (OR 0.15), and eye protection (OR 0.18). In addition, only 32.8% of PCPs adopted an adequate business continuity plan (BCP). After controlling for institutional setting, reading the national preparedness plan was significantly associated with establishment of a BCP (OR 5.86), and with knowledge of how to transfer a swab specimen to a local medical laboratory (OR 5.60). CONCLUSIONS: With regard to PPE availability, PCPs (especially clinic-based PCPs) were not adequately prepared for the influenza pandemic. Awareness of the national pandemic preparedness plan is likely to promote prefecture-wide implementation of BCPs and surveillance activity.


title: Chapter 6 Epidemiology and Control of Viral Diseases

text: Publisher Summary Epidemiology is the study of the determinants, dynamics, and distribution of diseases in populations. The risk of infection and disease in an animal or animal population is determined by characteristics of the virus, the host and host population, and behavioral, environmental, and ecological factors that affect virus transmission from one host to another. Epidemiology, which is part of the science of population biology, attempts to meld these factors into a unified population-based perspective. The word epidemiology is widely used now no matter what host is concerned; the words endemic, epidemic, and pandemic are used to characterize disease states in human populations, and enzootic, epizootic, and panzootic are their equivalents in animal populations. By introducing quantitative measurements of disease trends, epidemiology has come to have a major role in advancing our understanding of the nature of diseases and in alerting and directing disease-control activities. Epidemiologic study is also effective in clarifying the role of viruses in the etiology of diseases, in understanding the interaction of viruses with environmental determinants of disease, in determining factors affecting host susceptibility, in unraveling modes of transmission, and in large-scale testing of vaccines and drugs. The case definition is a critical component of rates and proportions that should be standardized to allow comparison of disease occurrence in different populations and subpopulations. Criteria can be specified for confirmed, probable, and possible cases, depending on whether the selected criteria are pathognomonic for the viral disease of interest and whether laboratory results are available for all cases. Different case definitions can be specified at the individual animal and at the aggregate level.


Co-infection of MERS-CoV and SARS-CoV-2 in the same host: a silent threat


title: Encephalitis diagnosis using metagenomics: application of next generation sequencing for undiagnosed cases

text: Abstract Background Current estimates suggest that even in the most resourced settings, the aetiology of encephalitis is identified in less than half of clinical cases. It is acknowledged that filling this gap needs a combination of rigorous sampling and improved diagnostic technologies. Next generation sequencing (NGS) methods are powerful tools with the potential for comprehensive and unbiased detection of pathogens in clinical samples. We reviewed the use of this new technology for the diagnosis of suspected infectious encephalitis, and discuss the feasibility for introduction of NGS methods as a frontline diagnostic test. Methods A systematic literature review was performed, using MESH and text word searches for variants of “sequencing” and “encephalitis” in Medline and EMbase, and searching bibliographies and citations using the Web of Science database. Two authors independently reviewed, extracted and summarised data. Findings The review identified 25 articles reporting 44 case reports of patients with suspected encephalitis for whom NGS was used as a diagnostic tool. We present the data and highlight themes arising from these cases. There are no randomly controlled trials to assess the utility of NGS as a diagnostic tool. Interpretation There is increasing evidence of a role for NGS in the work-up of undiagnosed encephalitis. Lower costs and increasing accessibility of these technologies will facilitate larger studies of these patients. We recommend NGS should be considered as a front-line diagnostic test in chronic and recurring presentations and, given current sample-to-result turn-around times, as second-line in acute cases of encephalitis.


title: Molecular epidemiology of bovine noroviruses in South Korea

text: Abstract Since the prevalence of bovine norovirus (BNoV) and their genetic diversity have only been reported in the USA, England, Germany and The Netherlands, this study examined the prevalence and genetic diversity of BNoVs in diarrheic calves in South Korea using 645 diarrheic fecal specimens from calves by RT-PCR and nested PCR assays. Overall, 9.3% of the diarrheic fecal samples tested positive for BNoVs by either RT-PCR or nested PCR, of which 5.9% samples also tested positive for other enteric pathogens including the bovine coronavirus, bovine viral diarrhea virus, bovine torovirus, bovine groups A, B and C rotaviruses, bovine enteric Nebraska-like calicivirus and Escherichia coli. The genetic diversity was determined by direct sequencing of the partial RdRp region of 12 BNoVs detected from the fecal samples by nested PCR. Among the BNoVs examined, one Korean BNoV strain had the highest nucleotide (86.8%) and amino acid (99.1%) identity with the genotype 1 BNoV (GIII-1) strain, while the remaining 11 Korean BNoVs shared a higher nucleotide (88.0–90.5%) and amino acid (93.5–99.1%) identity with the genotype 2 BNoV (GIII-2) strains. The phylogenetic data for the nucleotide and amino acid sequences also demonstrated that one Korean BNoV strain clustered with GIII-1 but the remaining eleven strains clustered with GIII-2. In conclusion, BNoV infections are endemic and there are two distinct genotypes with GIII-2 being the main genotype circulating in the calf population in South Korea.


title: Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon

text: OBJECTIVE: Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI. RESULTS: Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36–100% and 98.35–100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.


The Petri-Dish Effect


title: Efficacy and immunogenicity of recombinant swinepox virus expressing the A epitope of the TGEV S protein

text: Abstract To explore the possibility of developing a vaccine against transmissible gastroenteritis virus (TGEV) infection, a recombinant swinepox virus (rSPV-SA) expressing a TGEV protective antigen has been constructed. Immune responses and protection efficacy of the vaccination vector were assessed in both mice and pig models. An indirect ELISA assay suggested that when mice were vaccinated with rSPV-SA, the level of IgG against TGEV was enhanced dramatically. The cytokine assays were employed and the results indicated that both the Th1-type and Th2-type cytokine levels raised after vaccination with rSPV-SA in mice models. Results from the passive immunity protection test of new born piglets demonstrated that the recombinant live-vector vaccine, rSPV-SA, could 100% protect piglets from the SPV infection, and there was no significant clinical symptom in the rSPV-SA treatment group during this experiment. The data suggest that the novel recombinant swinepox virus is a potential vaccine against TGEV infection.


title: Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes

text: BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment. FINDINGS: By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection. CONCLUSION: Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.


title: Pandemic March: 2019 Coronavirus Disease’s First Wave Circumnavigates the Globe

text: OBJECTIVE: March 2020 was a pivotal month for the worldwide geographic and numeric expansion of the first wave of Coronavirus Disease 2019 (COVID-19). We examined the major storylines that depicted this explosive spread of COVID-19 around the globe. METHODS: A detailed review of World Health Organization (WHO) situation reports, surveillance summaries, and online resources allowed us to quantify the increases in cases and deaths by region and by country throughout the month of March 2020. RESULTS: During March, COVID-19 was officially declared by the WHO to be a pandemic. COVID-19 emerged from a focalized outbreak in the Western Pacific Region and rapidly proliferated across all continents worldwide. Globally, cumulative numbers of confirmed cases increased by a factor of nine throughout the month. During the entire month, cases rose exponentially throughout Europe. Starting in mid-March, confirmed cases accelerated coast-to-coast throughout the United States and, on March 26, the United States surpassed all other nations to rank first in numbers of cases. COVID-19 mortality lagged several weeks behind but by month’s end, death tolls were also rising exponentially. CONCLUSION: March 2020 was a consequential month when the COVID-19 pandemic wrapped completely around the planet, with outbreaks erupting in most nations worldwide.


title: State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans

text: Background: Between September 2012 and 22 October 2013, 144 laboratory-confirmed and 17 probable MERS-CoV cases from nine countries were notified to WHO. Methods: We summarize what is known about the epidemiology, virology, phylogeny and emergence of MERS-CoV to inform public health policies. Results: The median age of patients (n=161) was 50 years (range 14 months to 94 years), 64.5% were male and 63.4% experienced severe respiratory disease. 76.0% of patients were reported to have ≥1 underlying medical condition and fatal cases, compared to recovered or asymptomatic cases were more likely to have an underlying condition (86.8% vs. 42.4%, p<0.001). Analysis of genetic sequence data suggests multiple independent introductions into human populations and modelled estimates using epidemiologic and genetic data suggest R0 is <1, though the upper range of estimates may exceed 1. Index/sporadic cases (cases with no epidemiologic-link to other cases) were more likely to be older (median 59.0 years vs. 43.0 years, p<0.001) compared to secondary cases, although these proportions have declined over time. 80.9% vs. 67.2% of index/sporadic and secondary cases, respectively, reported ≥1 underlying condition. Clinical presentation ranges from asymptomatic to severe pneumonia with acute respiratory distress syndrome and multi-organ failure. Nearly all symptomatic patients presented with respiratory symptoms and 1/3 of patients also had gastrointestinal symptoms. Conclusions: Sustained human-to-human transmission of MERS-CoV has not been observed. Outbreaks have been extinguished without overly aggressive isolation and quarantine suggesting that transmission of virus may be stopped with implementation of appropriate infection control measures.


title: A survey of the preparedness for an influenza pandemic of general practitioners in the West Midlands, UK

text: There is a lack of evidence regarding the preparedness of general practitioners (GPs) to respond to pandemic influenza. A postal questionnaire survey was conducted to explore the self-perceived pandemic preparedness of GPs in the West Midlands, United Kingdom, and to determine differences between urban and non-urban GPs. The postal questionnaire was sent out to 773 GPs in November 2005, and a reminder was sent in January 2006. In all, 427/773 (55%) questionnaires were returned, and 56% of respondents were aware of influenza pandemic preparedness plans. Approximately one-quarter of respondents (28%, 114/401) thought the response of their practice to a pandemic event would be very poor/poor. Non-urban GPs were significantly more likely to rate the response of their practice to a pandemic as likely to be poor (OR 3.01, 95%CI 1.03–8.76) and were less likely to be aware of pandemic preparedness plans (OR 0.62, 95%CI 0.39–0.99). Non-urban GPs were also significantly more likely to feel less confident in their ability to explain to their patients what to do and why during an influenza pandemic than GPs based in urban areas (OR 4.68, 95%CI 1.78–12.31). GPs rating of the odds of a pandemic affecting the United Kingdom did not differ significantly by geographic location. The results of this paper can be used to inform and influence public health policy and as evidence of a need to provide additional education and training to improve pandemic preparedness among GPs, in particular those in non-urban areas.


title: Effectiveness of Common Fabrics to Block Aqueous Aerosols of Virus-like Nanoparticles

text: [Image: see text] Layered systems of commonly available fabric materials can be used by the public and healthcare providers in face masks to reduce the risk of inhaling viruses with protection that is about equivalent to or better than the filtration and adsorption offered by 5-layer N95 respirators. Over 70 different common fabric combinations and masks were evaluated under steady-state, forced convection air flux with pulsed aerosols that simulate forceful respiration. The aerosols contain fluorescent virus-like nanoparticles to track transmission through materials that greatly assist the accuracy of detection, thus avoiding artifacts including pore flooding and the loss of aerosol due to evaporation and droplet breakup. Effective materials comprise both absorbent, hydrophilic layers and barrier, hydrophobic layers. Although the hydrophobic layers can adhere virus-like nanoparticles, they may also repel droplets from adjacent absorbent layers and prevent wicking transport across the fabric system. Effective designs are noted with absorbent layers comprising terry cloth towel, quilting cotton, and flannel. Effective designs are noted with barrier layers comprising nonwoven polypropylene, polyester, and polyaramid.


title: Between Fear and Courage: Attitudes, Beliefs, and Behavior of Liver Transplantation Recipients and Waiting List Candidates during the COVID‐19 Pandemic

text: Patients with chronic liver disease and patients after solid organ transplantation (SOT) are vulnerable to severe Coronavirus Disease 2019 (COVID‐19). We evaluated fears, attitudes, and opinions associated with COVID‐19 in 365 SOT recipients (95% liver, 5% pancreas/kidney), 112 SOT candidates, and 394 immediate household contacts in two German transplant centers. Seven (1.5%) patients and 10 (2.5%) controls had contact to confirmed COVID‐19 cases. Fear of infection with SARS‐CoV‐2 was expressed by 65% SOT recipients and by 55% SOT candidates. SOT recipients had higher levels of fear of infection and more often wore personal protective gear than household controls. Female gender, steroid treatment, and using the local newspaper as a primary source of information were independently associated with expressed fear of infection in SOT recipients. Younger age and more recent transplantation correlated with concerns of severe COVID‐19 expressed by patients and with concerns of worse medical care expressed by household controls. One third of the patients expressed fear that immunosuppression could worsen COVID‐19 but only 15% used the transplantation center as a source of information. These data show that fears associated with the SARS‐CoV‐2 pandemic are frequently expressed but measures to prevent infection are frequently followed patients before and after SOT.


title: The Pan London Emergency Cardiac Surgery service: Coordinating a response to the COVID‐19 pandemic

text: Over the last 4 months, the novel coronavirus, SARS‐CoV‐2, has caused a significant economic, political, and public health impact on a global scale. The natural history of the disease and surge in the need for invasive ventilation has required the provision of intensive care beds in London to be reallocated. NHS England have proposed the formation of a Pan‐London Emergency Cardiac surgery (PLECS) service to provide urgent and emergency cardiac surgery for the whole of London. In this initial report, we outline our experience of setting up and delivering a pan‐regional service for the delivery of urgent and emergency cardiac surgery with a focus on maintaining a COVID‐free in‐hospital environment. In doing so, we hope that other regions can use this as a starting point in developing their own region‐specific pathways if the spread of coronavirus necessitates similar measures be put in place across the United Kingdom.


title: Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes

text: In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)—the proteasome holoenzymes and a number of ubiquitin ligases—play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity. Furthermore, the replication capacity of X4- and R5-tropic HIV-1(NL4-3) in human lymphatic tissue is decreased upon treatment with these inhibitors without affecting cell viability. Most strikingly, combinatory treatment with DIs and proteasome inhibitors synergistically blocks virus replication at concentrations where mono-treatment was ineffective, indicating that DIs can boost the therapeutic effect of proteasome inhibitors. In addition, P22077 and PR-619 increase the polyubiquitination of Gag and thus its entry into the UPS and the major histocompatibility complex (MHC)-I pathway. In summary, our data point towards a model in which specific inhibitors of DUBs not only interfere with virus spread but also increase the immune recognition of HIV-1 expressing cells.


title: Reliable and Standardized Animal Models to Study the Pathogenesis of Bluetongue and Schmallenberg Viruses in Ruminant Natural Host Species with Special Emphasis on Placental Crossing

text: Starting in 2006, bluetongue virus serotype 8 (BTV8) was responsible for a major epizootic in Western and Northern Europe. The magnitude and spread of the disease were surprisingly high and the control of BTV improved significantly with the marketing of BTV8 inactivated vaccines in 2008. During late summer of 2011, a first cluster of reduced milk yield, fever, and diarrhoea was reported in the Netherlands. Congenital malformations appeared in March 2012 and Schmallenberg virus (SBV) was identified, becoming one of the very few orthobunyaviruses distributed in Europe. At the start of both epizootics, little was known about the pathogenesis and epidemiology of these viruses in the European context and most assumptions were extrapolated based on other related viruses and/or other regions of the World. Standardized and repeatable models potentially mimicking clinical signs observed in the field are required to study the pathogenesis of these infections, and to clarify their ability to cross the placental barrier. This review presents some of the latest experimental designs for infectious disease challenges with BTV or SBV. Infectious doses, routes of infection, inoculum preparation, and origin are discussed. Particular emphasis is given to the placental crossing associated with these two viruses.


COVID-19 Illness and Heart Failure A Missing Link?


title: The Effect of 13-Valent Pneumococcal Conjugate Vaccine on the Serotype Distribution and Antibiotic Resistance Profiles in Children With Invasive Pneumococcal Disease

text: BACKGROUND: Invasive pneumococcal disease (IPD) continues to be a significant burden in children despite the implementation of two generations of conjugate vaccines. Serotype replacement by nonvaccine serotypes is reported in multiple areas around the world. This study is a continuation of previous studies and describes the incidence, serotype distribution, and antibiotic resistance pattern of Streptococcus pneumoniae serotypes causing IPD at Children's Medical Center Dallas after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Streptococcus pneumoniae isolates from normally sterile sites were collected from January 1, 1999 to June 30, 2014. Demographic and clinical information was extracted for analysis. Incidence of IPD was calculated using inpatient and emergency center admissions to Children's Medical Center of Dallas as the denominator. Isolates were serotyped and penicillin/cefotaxime susceptibilities were determined. Selected nontypeable isolates were further characterized by multilocus sequence typing. A χ(2) test and the Cochran–Armitage Trend Test for trend analysis were used to evaluate change in serotype and antibiotic susceptibility patterns over time. RESULTS: Comparison of the different study periods showed a significant reduction in the incidence of IPD in PCV13 era compared with prevaccine era and PCV7 era (P < .05). Children younger than 24 months showed the largest reduction of disease incidence. More than 40% of patients with IPD had a documented comorbidity. Cases of pneumonia continued to decrease in the PCV13 era (P < .002). The most common non-PCV13 serotypes after vaccine introduction were as follows: 23B, 6C, 23A, 9N/L, and 12. Penicillin resistance by meningitis breakpoint decreased significantly in the PCV13 era. CONCLUSIONS: After introduction of PCV13 in Dallas, incidence of IPD caused by strains contained in the vaccine and penicillin resistance continued to decrease. Serotype replacement phenomena and persistence of PCV7 serotypes were documented. Patients with comorbidities represented a large percentage of patients with IPD. Concerns for geographic variation in serotype replacement phenomena arise from the present study.


title: CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV)

text: In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities. © RSNA, 2020


title: Development of allergy in children I. Association with virus infections

text: Abstract Children born into allergic families, with two allergic parents, are at high risk of developing allergy within the first 5 years of life. In order to observe possible external factors in the sensitization process, a prospective study of 13 such children was done, in which serial clinical and immunologic observations were made at 3- to 6-month intervals over a period of 1 to 4 yr. Eleven of these children are now clinically allergic; 5 have asthma. Immunologic evidence for allergic sensitization was observed in these 11 children by RAST, antigen-induced leukocyte histamine release, lymphoblastogenesis, and rise in serum IgE. Upper respiratory infections (URI) occurred in these 11 allergic children 1 to 2 months prior to the onset of allergic sensitization. In 10 of these 11 URI children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced. This coincidence suggests that certain viruses may contribute to the allergic sensitization process.


title: Cardiac dysfunction and shock in pediatric patients with COVID-19

text: Abstract The 2019 novel coronavirus (COVID-19) has been reported to cause significant morbidity in adults with reportedly a lesser impact on children. Cardiac dysfunction has only been described in adults thus far. We describe three cases of previously healthy children presenting with shock and COVID-19 related cardiac inflammation.


title: Pandemic Influenza: A Potential Role for Statins in Treatment and Prophylaxis

text: The next influenza pandemic may be imminent. Because antiviral agents and vaccines will be unavailable to people in most countries, we need to determine whether other agents could offer clinical benefits. Influenza is associated with an increase in acute cardiovascular diseases, and influenza viruses induce proinflammatory cytokines. Statins are cardioprotective and have anti-inflammatory and immunomodulatory effects, and they thus might benefit patients with influenza. This hypothesis should be evaluated by using administrative databases to search for reduced rates of hospitalization and death due to influenza-related conditions among people taking statins. These studies should be followed by laboratory studies of statins in animal and cell-based models of influenza virus infection and, later, by clinical trials. Positive results from such studies would provide physicians in all countries with something to offer patients for treatment and prophylaxis of pandemic influenza. Generic statins will be widely distributed and inexpensive. They might be the only agents that could alter the course of a global pandemic.


title: Viral Protease Inhibitors

text: This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufficiently ubiquitous that treating an acute infection would be beneficial even if the infection was ultimately self-limiting. Protease inhibitor development is most advanced for hepatitis C virus (HCV), and we also provide a review of HCV NS3/4A serine protease inhibitor development, including combination therapy and resistance. Finally, we discuss other viral proteases as potential drug targets, including those from Dengue virus, cytomegalovirus, rhinovirus, and coronavirus.


title: How Did COVID-19 Affect Firms’ Access to Public Capital Markets?

text: We find that bond issues have substantially increased since the onset of the COVID-19 crisis in calendar week 12 (March 16–20) for bonds rated A or higher, but surprisingly also for bonds rated BBB or lower. In contrast to existing evidence on bond maturities in economic downturns, we document that maturities exceed those of bonds issued before by the same firms as well as the average maturities during normal times. Determinants of corporate bond spreads substantially differ between COVID-19 and normal times. Most prominently, asset tangibility has a highly significant negative effect on spreads during normal times. During COVID-19, this is reversed, especially in industries heavily affected by lockdown measures, reflecting the inflexibility associated with fixed assets. A different picture emerges for equity issues, which slowed considerably during the first 4 weeks of the pandemic, before accelerating again. Capital raised during COVID-19 via equity issues is approximately 5% of capital raised via bond issues.


Hajj, Umrah, and the neglected tropical diseases


title: Comparative evaluation of a laboratory-developed real-time PCR assay and RealStar® Adenovirus PCR Kit for quantitative detection of human adenovirus

text: BACKGROUND: Human adenoviruses are common causes of community-acquired respiratory tract and enteric infections. Severe disseminated infections with high mortality rates may be seen in immunocompromised individuals. An accurate and cost-effective quantitative assay is essential not only for laboratory diagnosis of adenoviral infections, but also for monitoring of response to antiviral treatment. The diagnostic performance of an in-house quantitative polymerase chain reaction assay was compared to a commercial system. METHODS: The analytical sensitivity, specificity, linearity, precision and accuracy of an in-house adenovirus quantitative polymerase chain reaction assay were evaluated against the RealStar® Adenovirus PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany), using 122 clinical specimens and 18 proficiency testing samples. RESULTS: Linear regression analysis of the quantitative results by the in-house assay showed the dynamic range from 2.60 to 9 log(10) (plasma) and 2.94 to 9 log(10) (viral transport medium) copies/mL, with the coefficient of determination (R(2)) of 0.996 and 0.998, respectively. A dilution series demonstrated the limits of detection and lower limits of quantification for plasma were 2.06 log(10) and 2.60 log(10) copies/mL and those for viral transport medium were 2.31 log(10) and 2.94 log(10) copies/mL respectively. The precision of the in-house assay was highly reproducible among runs with coefficients of variance ranging from 0.07 to 3.21% for plasma and 0.17% to 2.11% for viral transport medium. A comparison of 52 matched samples showed an excellent correlation between the quantitative viral loads measured by the in-house assay and the RealStar® Adenovirus PCR Kit (R(2) = 0.984), with an average bias of − 0.16 log(10) copies/mL. CONCLUSIONS: The in-house adenovirus assay is a sensitive and reliable assay with lower cost for the detection and quantification of adenoviral DNA when compared to the RealStar® Adenovirus PCR Kit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1059-7) contains supplementary material, which is available to authorized users.


title: Cyclophilin–CD147 interactions: a new target for anti-inflammatory therapeutics

text: CD147 is a widely expressed plasma membrane protein that has been implicated in a variety of physiological and pathological activities. It is best known for its ability to function as extracellular matrix metalloproteinase inducer (hence the other name for this protein, EMMPRIN), but has also been shown to regulate lymphocyte responsiveness, monocarboxylate transporter expression and spermatogenesis. These functions reflect multiple interacting partners of CD147. Among these CD147-interacting proteins cyclophilins represent a particularly interesting class, both in terms of structural considerations and potential medical implications. CD147 has been shown to function as a signalling receptor for extracellular cyclophilins A and B and to mediate chemotactic activity of cyclophilins towards a variety of immune cells. Recent studies using in vitro and in vivo models have demonstrated a role for cyclophilin–CD147 interactions in the regulation of inflammatory responses in a number of diseases, including acute lung inflammation, rheumatoid arthritis and cardiovascular disease. Agents targeting either CD147 or cyclophilin activity showed significant anti-inflammatory effects in experimental models, suggesting CD147–cyclophilin interactions may be a good target for new anti-inflammatory therapeutics. Here, we review the recent literature on different aspects of cyclophilin–CD147 interactions and their role in inflammatory diseases.