title: RNA: interactions drive functionalities

text: RNA is produced from the majority of human genomic sequences, although only a relatively small portion of these transcripts has known functions. Diverse RNA species interact with RNA, DNA, proteins, lipids, and metabolites to form intricate molecular networks. In this review, we attempt to delineate diverse RNA functions by interaction types between RNA and other macromolecules. Through such interactions RNAs participate in essentially every major molecular function and process, including information flow and storage, environment sensing, signal transduction, and gene regulation at transcriptional and posttranscriptional levels. Through such interactions, RNAs promote or inhibit diverse biological processes, and act as catalyzer or quencher to modulate the pace of these progresses. Alterations and personal variations of these interactions are mechanistically coupled with disease etiology and phenotypical variations for clinical use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-019-05230-7) contains supplementary material, which is available to authorized users.


title: The Asia Pacific Academic Consortium for Global Public Health and Medicine: Stabilizing South-South Academic Collaboration

text: Developmental strategies over the last 4 decades have generally tended to transfer knowledge and technology along north–south axes as trickle-down theories in development, especially in health knowledge transfers, prevailed. Limited efforts in development assistance for health (DAH) were made to promote south-south cooperation for basic health needs. Globalization with increased educational networks and development health assistance has enhanced the potential for more effective south-south partnerships for health. The stages of development in a consortium and key catalysts in the metamorphosis to a south-south partnership are identified: leadership, resources, expertise, visibility participation, and dynamism of a critical mass of young professionals.


title: Identification of peptide domains involved in the subcellular localization of the feline coronavirus 3b protein

text: Feline coronavirus (FCoV) has been identified as the aetiological agent of feline infectious peritonitis (FIP), a highly fatal systemic disease in cats. FCoV open reading frame 3 (ORF3) encodes accessory proteins 3a, 3b and 3 c. The FCoV 3b accessory protein consists of 72 amino acid residues and localizes to nucleoli and mitochondria. The present work focused on peptide domains within FCoV 3b that drive its intracellular trafficking. Transfection of different cell types with FCoV 3b fused to enhanced green fluorescent protein (EGFP) or 3×FLAG confirmed localization of FCoV 3b in the mitochondria and nucleoli. Using serial truncated mutants, we showed that nucleolar accumulation is controlled by a joint nucleolar and nuclear localization signal (NoLS/NLS) in which the identified overlapping pat4 motifs (residues 53–57) play a critical role. Mutational analysis also revealed that mitochondrial translocation is mediated by N-terminal residues 10–35, in which a Tom20 recognition motif (residues 13–17) and two other overlapping hexamers (residues 24–30) associated with mitochondrial targeting were identified. In addition, a second Tom20 recognition motif was identified further downstream (residues 61–65), although the mitochondrial translocation evoked by these residues seemed less efficient as a diffuse cytoplasmic distribution was also observed. Assessing the spatiotemporal distribution of FCoV 3b did not provide convincing evidence of dynamic shuttling behaviour between the nucleoli and the mitochondria.


title: Co-lethality studied as an asset against viral drug escape: the HIV protease case

text: BACKGROUND: Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. RESULTS: From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. CONCLUSIONS: These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. REVIEWERS: This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.


title: Porcine Hemagglutinating Encephalomyelitis Virus: A Review

text: The porcine hemagglutinating encephalomyelitis virus (PHEV) is classified as a member of genus Betacoronavirus, family Coronaviridae, sub-family Cornavirinae, and order Nidovirales. PHEV shares the same genomic organization, replication strategy, and expression of viral proteins as other nidoviruses. PHEV produces vomiting and wasting disease (VWD) and/or encephalomyelitis, being the only known neurotropic coronavirus affecting pigs. First clinical outbreak was reported in 1957 in Ontario, Canada. Although pigs are the only species susceptible to natural PHEV infections, the virus displays neurotropism in mice and Wistar rats. Clinical disease, morbidity, and mortality is age-dependent and generally reported only in piglets under 4 weeks old. The primary site of replication of PHEV in pigs is the respiratory tract, and it can be further spread to the central nervous system through the peripheral nervous system via different pathways. The diagnosis of PHEV can be made using a combination of direct and indirect detection methods. The virus can be isolated from different tissues within the acute phase of the clinical signs using primary and secondary pig-derived cell lines. PHEV agglutinates the erythrocytes of mice, rats, chickens, and several other animals. PCR-based methods are useful to identify and subsequently isolate animals that are actively shedding the virus. The ability to detect antibodies allows producers to know the status of first-litter gilts and evaluate their risk of tier offspring to infection. PHEV is highly prevalent and circulates subclinically in most swine herds worldwide. PHEV-related disease is not clinically relevant in most of the swine-producing countries, most likely because of dams are immune to PHEV which may confer passive immunity to their offspring. However, PHEV should be considered a major source of economic loss because of the high mortality on farms with high gilt replacement rates, specific pathogen-free animals, and gnotobiotic swine herds. Thus, in the absence of current PHEV vaccines, promoting virus circulation on farms with early exposure to gilts and young sows could induce maternal immunity and prevent disease in piglets.


Origin and Evolution of the 2019 Novel Coronavirus


title: Three Taiwan's domestic family cluster infections of coronavirus disease 2019

text: Since the first case of coronavirus disease 2019 (COVID‐19) was identified in Taiwan 2020.01.21. Several family cluster infections were found later. This study aimed to report family cluster infections and observe subsequent development. We collected domestic family cluster infections among COVID‐19 confirmed cases from 21 January 2020 to 16 March 2020. There were three domestic family clusters infections in this period. The first cluster was cases 19 to 23. The infectious source was a Taiwanese passenger from Zhejiang. The second cluster was cases 24 to 26 and the third cluster was cases 27 to 32. The infectious sources of the latter clusters are currently uncertain. All contacts of three clusters have been isolated and no new confirmed cases have been identified to date. Some measures which have reduced the spread of these three clusters included: First, high suspicion of COVID‐19 for unexplained pneumonia is very important for early detection. Second, immediate epidemic investigation is taken especially COVID‐19 is infectious during the incubation period. Third, when the second and third clusters could not find infectious sources, CECC's press conference let the public know immediately the epidemic situation, so that people could raise their awareness and seek medical treatment or quarantine.


title: Analysis of the molecular mechanism of Pudilan (PDL) treatment for COVID-19 by network pharmacology tools

text: BACKGROUND: Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been clinically used as an anti-SARS-CoV-2 infectory agent in China for decades. PDL might also have therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified. METHODS: We used network pharmacology analysis and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform. RESULTS: PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It might inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C motif chemokine ligand 5 (CCL5), transforming growth factor-β1 (TGFβ1), and other proteins. PDL might moderate the immune system to shorten the course of the disease, delay disease progression, and reduce the mortality rate. CONCLUSION: PDL might have a therapeutic effect on COVID-19 through three aspects, including the moderate immune system, anti-inflammation, and anti-virus entry into cells.


title: Ultrastructural Characterization of Membrane Rearrangements Induced by Porcine Epidemic Diarrhea Virus Infection

text: The porcine epidemic diarrhea virus (PEDV) is a coronavirus (CoV) belonging to the α-CoV genus and it causes high mortality in infected sucking piglets, resulting in substantial losses in the farming industry. CoV trigger a drastic reorganization of host cell membranes to promote their replication and egression, but a detailed description of the intracellular remodeling induced by PEDV is still missing. In this study, we examined qualitatively and quantitatively, using electron microscopy, the intracellular membrane reorganization induced by PEDV over the course of an infection. With our ultrastructural approach, we reveal that, as most of CoV, PEDV initially forms double-membrane vesicles (DMVs) and convoluted membranes (CMs), which probably serve as replication/transcription platforms. Interestingly, we also found that viral particles start to form almost simultaneously in both the endoplasmic reticulum and the large virion-containing vacuoles (LVCVs), which are compartments originating from the Golgi, confirming that α-CoV assemble indistinguishably in two different organelles of the secretory pathway. Moreover, PEDV virons appear to have an immature and a mature form, similar to another α-CoV the transmissible gastroenteritis coronavirus (TGEV). Altogether, our study underlies the similarities and differences between the lifecycle of α-CoV and that of viruses belonging to other CoV subfamilies.


title: Middle East respiratory syndrome coronavirus experimental transmission using a pig model

text: Dromedary camels are the main reservoir of Middle East respiratory syndrome coronavirus (MERS‐CoV), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with MERS‐CoV. Animal‐to‐animal transmission in alpacas was reported, but evidence for transmission in other species has not been proved. This study explored pig‐to‐pig MERS‐CoV transmission experimentally. Virus was present in nasal swabs of infected animals, and limited amounts of viral RNA, but no infectious virus were detected in the direct contact pigs. No virus was detected in the indirect contact group. Furthermore, direct and indirect contact pigs did not develop specific antibodies against MERS‐CoV. Therefore, the role of pigs as reservoir is probably negligible, although it deserves further confirmation.


title: First environmental surveillance for the presence of SARS-CoV-2 RNA in wastewater and river water in Japan

text: Abstract Wastewater-based epidemiology is a powerful tool to understand the actual incidence of coronavirus disease 2019 (COVID-19) in a community because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can be shed in the feces of infected individuals regardless of their symptoms. The present study aimed to assess the presence of SARS-CoV-2 RNA in wastewater and river water in Yamanashi Prefecture, Japan, using four quantitative and two nested PCR assays. Influent and secondary-treated (before chlorination) wastewater samples and river water samples were collected five times from a wastewater treatment plant and three times from a river, respectively, between March 17 and May 7, 2020. The wastewater and river water samples (200–5000 mL) were processed by using two different methods: the electronegative membrane-vortex (EMV) method and the membrane adsorption-direct RNA extraction method. Based on the observed concentrations of indigenous pepper mild mottle virus RNA, the EMV method was found superior to the membrane adsorption-direct RNA extraction method. SARS-CoV-2 RNA was successfully detected in one of five secondary-treated wastewater samples with a concentration of 2.4 × 103 copies/L by N_Sarbeco qPCR assay following the EMV method, whereas all the influent samples were tested negative for SARS-CoV-2 RNA. This result could be attributed to higher limit of detection for influent (4.0 × 103–8.2 × 104 copies/L) with a lower filtration volume (200 mL) compared to that for secondary-treated wastewater (1.4 × 102–2.5 × 103 copies/L) with a higher filtration volume of 5000 mL. None of the river water samples tested positive for SARS-CoV-2 RNA. Comparison with the reported COVID-19 cases in Yamanashi Prefecture showed that SARS-CoV-2 RNA was detected in the secondary-treated wastewater sample when the cases peaked in the community. This is the first study reporting the detection of SARS-CoV-2 RNA in wastewater in Japan.


title: Anticipatory prescribing in community end-of-life care in the UK and Ireland during the COVID-19 pandemic: online survey

text: BACKGROUND: Anticipatory prescribing (AP) of injectable medications in advance of clinical need is established practice in community end-of-life care. Changes to prescribing guidelines and practice have been reported during the COVID-19 pandemic. AIMS AND OBJECTIVES: To investigate UK and Ireland clinicians’ experiences concerning changes in AP during the COVID-19 pandemic and their recommendations for change. METHODS: Online survey of participants at previous AP national workshops, members of the Association for Palliative Medicine of Great Britain and Ireland and other professional organisations, with snowball sampling. RESULTS: Two hundred and sixty-one replies were received between 9 and 19 April 2020 from clinicians in community, hospice and hospital settings across all areas of the UK and Ireland. Changes to AP local guidance and practice were reported: route of administration (47%), drugs prescribed (38%), total quantities prescribed (35%), doses and ranges (29%). Concerns over shortages of nurses and doctors to administer subcutaneous injections led 37% to consider drug administration by family or social caregivers, often by buccal, sublingual and transdermal routes. Clinical contact and patient assessment were more often remote via telephone or video (63%). Recommendations for regulatory changes to permit drug repurposing and easier community access were made. CONCLUSIONS: The challenges of the COVID-19 pandemic for UK community palliative care has stimulated rapid innovation in AP. The extent to which these are implemented and their clinical efficacy need further examination.


Competition law in times of crisis—tackling the COVID-19 challenge: a producer perspective


title: Genetic and biological characteristics of four novel recombinant avian infectious bronchitis viruses isolated in China

text: Abstract Infectious bronchitis viruses (IBVs) of GI-13 (793/B) and GI-19 (QX/LX4) lineages have been frequently detected in China in recent years. Naturally recombinant IBVs originating from the GI-13 and GI-19 lineages have also been isolated from chicken flocks with respiratory and renal problems in China. Thorough genetic and biological investigations of these recombinant viruses have led to speculation regarding their origin, evolution, and control. In order to confirm the previous results and further extend our understanding about the characteristics of the four recombinant IBV strains we had previously identified (I0718/17, I0722/17, I0724/17, and I0737/17), we conducted phylogenetic analysis by comparing their complete S1 gene sequences with those of 71 reference strains of different genotypes and lineages. We identified a close relationship between the S1 sequences of the four strains and those of GI-13 strains. The results of complete genome sequence analysis confirmed the previously identified recombination events in the four IBV strains and revealed additional recombination events in different genomic regions of strains I0718/17 and I0724/17, suggesting that the two strains originated from multiple recombination events between 4/91-like and YX10-like viruses. We comparatively evaluated the antigenicity, pathogenicity, and affinity of the four recombinant viruses and their deduced parental strains in the trachea and kidneys. Some of the strains showed comparable antigenic relatedness, pathogenicity, and affinity for the trachea and kidneys among each other and with their parental viruses; however, some of them showed varying biological characteristics. Point mutations observed in the receptor-binding domain and hypervariable region of the S1 subunit of the spike protein likely have an effect on these differences in biological characteristics, although the influence of other factors—such as host innate-immune responses and changes in genomic regions beyond the S1 protein—might also be responsible for such changes.


title: Real-time reverse transcription loop-mediated isothermal amplification for rapid detection of SARS-CoV-2

text: BACKGROUND: Highly sensitive real-time reverse transcription polymerase chain reaction (RT-qPCR) methods have been developed for the detection of SARS-CoV-2. However, they are costly. Loop-mediated isothermal amplification (LAMP) assay has emerged as a novel alternative isothermal amplification method for the detection of nucleic acid. METHODS: A rapid, sensitive and specific real-time reverse transcription LAMP (RT-LAMP) assay was developed for SARS-CoV-2 detection. RESULTS: This assay detected one copy/reaction of SARS-CoV-2 RNA in 30 min. Both the clinical sensitivity and specificity of this assay were 100%. The RT-LAMP showed comparable performance with RT-qPCR. Combining simplicity and cost-effectiveness, this assay is therefore recommended for use in resource resource-limited settings.


title: SARS-CoV-2 Infections in Children — Multi-Center Surveillance, United States, January–March 2020

text: Previous reports of COVID-19 among US children have been based on health jurisdiction reporting. We performed SARS-CoV-2 testing on children enrolled in active, prospective, multi-center surveillance during January–March, 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2–positive cases were identified March 20–31 despite evidence of rising community circulation.


title: COVID-19 - Working as a hygienist or therapist

text: The Coronavirus (COVID-19) global pandemic has posed significant challenges for all members of the dental team Whilst dentists are considered to be one of the most exposed and high-risk occupations, dental hygienists and dental therapists are in fact at even greater risk 1 Dental hygienists and therapists are integral members of the dental team and play a key role in preventing, treating disease and maintaining oral health Whilst we are uncertain on how the pandemic will affect the future of dentistry, we need to ensure that hygienists and therapists are kept at the forefront There are almost six times as many dentists as hygienists2 so it's important to ensure the voice of hygienists and therapists is heard just as clearly as that of dentists


title: Animal tissue culture principles and applications

text: Animal cell culture technology in today’s scenario has become indispensable in the field of life sciences, which provides a basis to study regulation, proliferation, and differentiation and to perform genetic manipulation. It requires specific technical skills to carry out successfully. This chapter describes the essential techniques of animal cell culture as well as its applications.


Re: Ventilation-perfusion Scans During the Coronavirus (COVID-19) Outbreak


title: The Australian Institute of Sport Framework for Rebooting Sport in a COVID-19 Environment

text: Abstract Sport makes an important contribution to the physical, psychological and emotional well-being of Australians. The economic contribution of sport is equivalent to 2–3% of Gross Domestic Product (GDP). The COVID-19 pandemic has had devastating effects on communities globally, leading to significant restrictions on all sectors of society, including sport. Resumption of sport can significantly contribute to the re-establishment of normality in Australian society. The Australian Institute of Sport (AIS), in consultation with sport partners (National Institute Network (NIN) Directors, NIN Chief Medical Officers (CMOs), National Sporting Organisation (NSO) Presidents, NSO Performance Directors and NSO CMOs), has developed a framework to inform the resumption of sport. National Principles for Resumption of Sport were used as a guide in the development of ‘the AIS Framework for Rebooting Sport in a COVID-19 Environment’ (the AIS Framework); and based on current best evidence, and guidelines from the Australian Federal Government, extrapolated into the sporting context by specialists in sport and exercise medicine, infectious diseases and public health. The principles outlined in this document apply to high performance/professional, community and individual passive (non-contact) sport. The AIS Framework is a timely tool of minimum baseline of standards, for ‘how’ reintroduction of sport activity will occur in a cautious and methodical manner, based on the best available evidence to optimise athlete and community safety. Decisions regarding the timing of resumption (the ‘when’ ) of sporting activity must be made in close consultation with Federal, State/Territory and Local Public Health Authorities. The priority at all times must be to preserve public health, minimising the risk of community transmission.


title: A quasi-experiment on using guided mobile learning interventions in ESL classrooms: Time use and academic performance

text: This quasi-experimental study examined a guided learning approach towards the use of mobile devices and investigated the performance of language learners who were guided in the usage. A total of 419 students from two faculties were invited to participate in this 8-week intervention, 155 participants in the control group and 264 in the experimental group. In the experimental group, the researchers incorporated guided activities Module Intervention Model (MIM) using mobile devices into the ESL lessons whereas the control group lessons were without guided activities. Participants from both groups were asked to record their daily mobile device use for activities related to English language learning using an online form. These data were compared to the results of the tests conducted pre- and post-treatment. At the end of the study, students who received guided language activities utilizing the mobile devices had significantly higher levels of language performance than control group students. However, treatment group students who spent more time using mobile devices to learn the language did not display better performance compared to those who spent minimal time. This finding re-established the importance of guided activities as intervention to facilitate students’ learning and points to the need for curricular modernization and faculty development in the instructional use of technology. Due to the increased need for online instruction precipitated by “social distancing and isolation’ required to overcome the coronavirus pandemic, the need for faculty to acquire skills in guided use of mobile devices for school-related learning is anticipated to be greater than ever.


Anti-viral surfaces could tackle COVID-19 crisis


title: Use of convalescent plasma therapy in SARS patients in Hong Kong

text: In order to evaluate the efficacy of convalescent plasma therapy in the treatment of patients with severe acute respiratory syndrome (SARS), 80 SARS patients were given convalescent plasma at Prince of Wales Hospital, Hong Kong, between 20 March and 26 May 2003. Good outcome was defined as discharge by day 22 following the onset of SARS symptoms. Poor outcome was defined as death or hospitalization beyond 22 days. A higher day-22 discharge rate was observed among patients who were given convalescent plasma before day 14 of illness (58.3% vs 15.6%; P<0.001) and among those who were PCR positive and seronegative for coronavirus at the time of plasma infusion (66.7% vs 20%; P=0.001).


title: Kidney transplantation and the lock‐down effect

text: Kidney transplantation might not be considered a life‐saving procedure as there are alternative forms of renal replacement, although it is superior in the long‐term life expectancy and overall costs. During COVID‐19 outbreak, we have to deal with the post‐immunosuppression COVID‐19 increased risk, a burden less prominent in the case of liver and heart transplant candidates, who eventually will die if not transplanted. Since kidney grafts can also be transplanted from a living donor, the suspended elective activity has had a major significant impact for this organ compared to the others.


title: Evaluation of novel coronavirus disease (COVID-19) using quantitative lung CT and clinical data: prediction of short-term outcome

text: BACKGROUND: Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. METHODS: From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. RESULTS: A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26–95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1–30) and 4.94 mg/L (range 0.1–28.3), respectively. Median VoD was 249.5 cm(3) (range 9.9–1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. CONCLUSIONS: Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.


title: Atg5 is Essential for Cellular Immunity in vivo and recruitment of a p47 GTPase to the Toxoplasma gondii Parasitophorous Vacuole in Macrophages

text: The physiologic importance of autophagy proteins for control of mammalian bacterial and parasitic infection in vivo is unknown. We show that expression of the essential autophagy protein Atg5 in granulocytes and macrophages is required for in vivo resistance to infection with L. monocytogenes and T. gondii. In primary macrophages, Atg5 was not required for IFNγ/LPS-mediated transcription, induction of nitric oxide, or inhibition of T. gondii replication. However, Atg5 was required for IFNγ/LPS-induced damage to the T. gondii parasitophorous vacuole membrane and parasite clearance. While we did not detect autophagosomes enveloping T. gondii, Atg5 was required for recruitment of the IFNγ-inducible p47 GTPase IIGP1 (Irga6) to the vacuole membrane. This work shows that Atg5 expression in phagocytic cells is essential for cellular immunity to intracellular pathogens in vivo and that an autophagy protein can participate in immunity and intracellular killing of pathogens via autophagosome-independent processes such as GTPase trafficking.


title: Physiological stress of intracellular Shigella flexneri visualized with a metabolic sensor fused to a surface-reporter system

text: Abstract When deleted of its N-terminal signal-reception domain, the broad host range σ54-dependent transcriptional regulator XylR, along with its cognate promoter Pu, becomes a sensor of the metabolic stress of the carrier bacteria. We have employed a surface reporter system to visualize the physiological status of intracellular Shigella flexneri during infection of Henle 407 cells in culture. To this end, the xylRΔA gene has been engineered adjacent to a bicistronic transcriptional fusion of Pu to a lamB variant tagged with a short viral sequence (cor) and β-galactosidase (lacZ). The accessibility of the cor epitope to the externalmost medium and the expression of Pu in the bacterial population was confirmed, respectively, with immunomagnetic beads and the sorting of Escherichia coli cells treated with a fluorescent antibody. Intracellular Shigella cells expressed the Pu–lamB/cor–lacZ reporter at high levels, suggesting that infectious cells endure a considerable metabolic constraint during the invasion process.


title: Human adenovirus infection in children with acute respiratory tract disease in Guangzhou, China

text: Acute respiratory infections (ARI) are the major worldwide health problem due to associated high morbidity and mortality rates. Adenovirus (Adv) is one of the most common causes of viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Our aims were to find out the status of Adv infection in children <14 years with ARI, analyze the epidemiology and clinical characteristics among the Adv‐infected children in Guangzhou, China, and to provide some basis for the research of Adv. The throat and pharyngeal swabs were collected among the children with acute respiratory tract infections in outpatient department from September 2006 to August 2008. The samples were analyzed by PCR and the sequences were blasted with the sequences of Adv in GenBank. Clinical data were analyzed along with virological data by using appropriate statistical methods. Adv was detected in 25 out of 512 (4.9%) children. The genome types of 23 samples were determined after analysis of the gene sequence. The most prevalent Adv type was species B type 3. Among the patients, 10 were of Ad3 (43.5%), three were of Ad1 (1.3%), five were of species C Ad2 (21.7%), and five were of species E Ad4 (21.7%). A higher incidence of positive results was found during the summer season, thus showing a pattern of seasonality. There exists Adv infection in children with acute respiratory system diseases in Guangzhou area. No significant differences were found among different age groups and gender groups. Co‐infections with other respiratory virus were detected in 64% of the Adv positive samples.


Inevitable or avoidable? Despite the lessons of history, the world is not yet ready to face the next great plague


title: The impact of skin banking and the use of its cadaveric skin allografts for severe burn victims in Singapore

text: The skin banking programme was set-up in Singapore in 1998 to provide a ready source of allografts for patients with severe burns. The process and problems in establishing a local skin bank will be described together with a retrospective review of skin allograft recipients to determine the efficacy of the programme. For the skin bank set-up, pertinent issues related to legislation, methods, logistics, quality assurance and donation rate are discussed. In this retrospective review, a comparison between patients who had early complete excision with skin allograft transplantation and those who received conventional staged excision and coverage, was analysed in terms of clinical profile and outcome using statistical methods. The former group presented a significant reduction of mortality rate and hospital stay by 29% and 10 days, respectively. The establishment of the skin bank has helped in the management of severe burn patients by facilitating early excision and allografting. In a Burn Centre, therefore, it is essential to have an ample supply of skin allograft for burn victims in readiness for mass disaster situations.


title: Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia

text: BACKGROUND: Primary ciliary dyskinesia can result from a number of different ciliary defects that adversely affect ciliary function resulting markedly reduced or absent mucociliary clearance. Improvement in diagnostic testing is an area of current research. During diagnostic evaluation of PCD we observed ciliated conical protrusions from part of the apical surface of ciliated cells in those diagnosed with PCD. The aim of this study was to investigate if this abnormality was specific to PCD. METHODS: Epithelial edges from 67 consecutively diagnosed PCD patients, 67 patients consecutively referred for PCD diagnostic testing in whom PCD was excluded, 22 with asthma and 18 with Cystic Fibrosis (CF) were studied retrospectively in a blinded manner using light microscopy. RESULTS: Forty six out of 67 patients with PCD had ciliated conical epithelial protrusions, whereas none were seen in patients where PCD was excluded, or in patients with asthma or CF. The sensitivity, specificity, positive predictive value and negative predictive value for the presence of the ciliated conical protrusions to predict a diagnosis of PCD were 76.5, 100, 100 and 77% respectively. CONCLUSIONS: Characteristic ciliated conical protrusions from ciliated epithelial cells maybe a useful pointer to the diagnosis of PCD. However, their absence does not exclude the diagnosis of PCD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0782-3) contains supplementary material, which is available to authorized users.


SARS-CoV-2-Infektion und Auge


title: Effect of selected gastrointestinal parasites and viral agents on fecal S100A12 concentrations in puppies as a potential comparative model

text: BACKGROUND: Previous data suggest that fecal S100A12 has clinical utility as a biomarker of chronic gastrointestinal inflammation (idiopathic inflammatory bowel disease) in both people and dogs, but the effect of gastrointestinal pathogens on fecal S100A12 concentrations is largely unknown. The role of S100A12 in parasite and viral infections is also difficult to study in traditional animal models due to the lack of S100A12 expression in rodents. Thus, the aim of this study was to evaluate fecal S100A12 concentrations in a cohort of puppies with intestinal parasites (Cystoisospora spp., Toxocara canis, Giardia sp.) and viral agents that are frequently encountered and known to cause gastrointestinal signs in dogs (coronavirus, parvovirus) as a comparative model. METHODS: Spot fecal samples were collected from 307 puppies [median age (range): 7 (4−13) weeks; 29 different breeds] in French breeding kennels, and fecal scores (semiquantitative system; scores 1−13) were assigned. Fecal samples were tested for Cystoisospora spp. (C. canis and C. ohioensis), Toxocara canis, Giardia sp., as well as canine coronavirus (CCV) and parvovirus (CPV). S100A12 concentrations were measured in all fecal samples using an in-house radioimmunoassay. Statistical analyses were performed using non-parametric 2-group or multiple-group comparisons, non-parametric correlation analysis, association testing between nominal variables, and construction of a multivariate mixed model. RESULTS: Fecal S100A12 concentrations ranged from < 24−14,363 ng/g. Univariate analysis only showed increased fecal S100A12 concentrations in dogs shedding Cystoisospora spp. (P = 0.0384) and in dogs infected with parvovirus (P = 0.0277), whereas dogs infected with coronavirus had decreased fecal S100A12 concentrations (P = 0.0345). However, shedding of any single enteropathogen did not affect fecal S100A12 concentrations in multivariate analysis (all P > 0.05) in this study. Only fecal score and breed size had an effect on fecal S100A12 concentrations in multivariate analysis (P < 0.0001). CONCLUSIONS: An infection with any single enteropathogen tested in this study is unlikely to alter fecal S100A12 concentrations, and these preliminary data are important for further studies evaluating fecal S100A12 concentrations in dogs or when using fecal S100A12 concentrations as a biomarker in patients with chronic idiopathic gastrointestinal inflammation.


title: FREQUENT AND PROLONGED SHEDDING OF BOCAVIRUS IN YOUNG CHILDREN ATTENDING DAYCARE

text: BACKGROUND: Little is known about HBoV persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms. METHODS: We performed HBoV testing on nasal swabs from a prospective, longitudinal study of respiratory illness in 119 children attending daycare. RESULTS: HBoV was detected in 70 children (59%), and in 106 (33%) of the 318 study illnesses. Another virus was detected in 76 HBoV+ illnesses (72%). Extended and intermittent shedding was observed, with consistent HBoV detection documented for up to 75 days. HBoV was detected in 20 of 45 asymptomatic enrollment samples (44%) and HBoV prevalence and viral load did not differ significantly between children with and without symptoms at enrollment. HBoV+ illnesses were longer than HBoV- illnesses (OR: 2.44 for symptoms > 7 days, 95% C.I. 1.41, 4.22) and illnesses with HBoV viral load ≥ 4 log-copies/mL required a visit to a health care provider more often than HBoV-illnesses (OR: 1.64, 95% C.I.: 1.02, 2.64). CONCLUSION: HBoV was more common in illnesses with greater severity. However, detection of HBoV was not associated with the presence of respiratory illness or with specific respiratory symptoms in this prospective study of infants and toddlers attending center-based daycare.


title: The probability of failing in detecting an infectious disease at entry points into a country

text: In a group of N individuals, carrying an infection with prevalence π, the exact probability P of failing in detecting the infection is evaluated when a diagnostic test of sensitivity s and specificity s′ is carried out on a sample of n individuals extracted without replacement from the group. Furthermore, the minimal number of individuals that must be tested if the probability P has to be lower than a fixed value is determined as a function of π. If all n tests result negative, confidence intervals for π are given both in the frequentistic and Bayesian approach. These results are applied to recent data for severe acute respiratory syndrome (SARS). The conclusion is that entry screening with a diagnostic test is rarely an efficacious tool for preventing importation of a disease into a country. Copyright © 2005 John Wiley & Sons, Ltd.


title: Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

text: The pandemic H1N1 2009 influenza virus has caused the first influenza pandemic of the 21st century, leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the illness. Advances in science and technology have allowed very detailed study on the pathogenesis of this novel virus, and many have already been published in less than a year after the start of the pandemic. Information generated from cell lines, animal models, and clinical data analysis has provided us with greater understanding of the behavior of this virus and the associated host response. The new knowledge will allow us to formulate scientifically sound and evidence-based management plans.


title: Spanish Influenza in Japanese Armed Forces, 1918–1920

text: With the recent outbreaks of avian influenza A (H5N1), the risk for the next influenza pandemic has increased. For effective countermeasures against the next pandemic, investigation of past pandemics is necessary. We selected cases diagnosed as influenza from medical records and hospitalization registries of Japanese army hospitals during 1918–1920, the Spanish influenza era, and investigated clinical features and circumstances of outbreaks. Admission lists showed a sudden increase in the number of inpatients with influenza in November 1918 and showed the effect of the first wave of this pandemic in Tokyo. The death rate was high (6%–8%) even though patients were otherwise healthy male adults.


title: Research in Nondomestic Species: Experiences in Reproductive Physiology Research for Conservation of Endangered Felids

text: Tremendous strides have been made in recent years to broaden our understanding of reproductive processes in nondomestic felid species and further our capacity to use this basic knowledge to control and manipulate reproduction of endangered cats. Much of that progress has culminated from detailed scientific studies conducted in nontraditional laboratory settings, frequently at collaborating zoological parks but also under more primitive conditions, including in the field. A mobile laboratory approach is described, which incorporates a diverse array of disciplines and research techniques. This approach has been extremely useful, especially for conducting gamete characterization and function studies as well as reproductive surveys, and for facilitating the development of assisted reproductive technology. With continuing advances in assisted reproduction in rare felids, more procedures are being conducted primarily as service-related activities, targeted to increase effectiveness of species propagation and population management. It can be a challenge for both investigators and institutional animal care and use committees (IACUCs) to differentiate these service-based procedures from traditional research studies (that require IACUC oversight). For research with rare cat species, multi-institutional collaboration frequently is necessary to gain access to scientifically meaningful numbers of study subjects. Similarly, for service-based efforts, the ability to perform reproductive procedures across institutions under nonstandard laboratory conditions is critical to applying reproductive sciences for managing and preserving threatened cat populations. Reproductive sciences can most effectively assist population management programs (e.g., Species Survival Plans) in addressing conservation priorities if these research and service-related procedures can be conducted "on the road" at distant national and international locales. This mobile laboratory approach has applications beyond endangered species research, notably for other scientific fields (e.g., studies of hereditary disease in domestic cat models) in which bringing the laboratory to the subject is of value.


title: Influenza virus variation in susceptibility to inactivation by pomegranate polyphenols is determined by envelope glycoproteins

text: Abstract Pomegranates have high levels of polyphenols (PPs) and may be a rich source of compounds with antiviral activity. We evaluated the direct anti-influenza activity of three commercially available pomegranate extracts: pomegranate juice (PJ), a concentrated liquid extract (POMxl), and a 93% PP powder extract (POMxp). The acidity of PJ and POMxl solutions contributed to rapid anti-influenza activity, but this was not a factor with POMxp. Studies using POMxp showed that 5min treatment at room temperature with 800μg/ml PPs resulted in at least a 3log reduction in the titers of influenza viruses PR8 (H1N1), X31 (H3N2), and a reassortant H5N1 virus derived from a human isolate. However, the antiviral activity was less against a coronavirus and reassortant H5N1 influenza viruses derived from avian isolates. The loss of influenza infectivity was frequently accompanied by loss of hemagglutinating activity. PP treatment decreased Ab binding to viral surface molecules, suggesting some coating of particles, but this did not always correlate with loss of infectivity. Electron microscopic analysis indicated that viral inactivation by PPs was primarily a consequence of virion structural damage. Our findings demonstrate that the direct anti-influenza activity of pomegranate PPs is substantially modulated by small changes in envelope glycoproteins.


title: The effects of a novel adjuvant complex/Eimeria profilin vaccine on the intestinal host immune response against live E. acervulina challenge infection

text: Abstract The effects of a novel adjuvant composed of Quil A, cholesterol, dimethyl dioctadecyl ammonium bromide, and Carbopol (QCDC) on protective immunity against avian coccidiosis following immunization with an Eimeria recombinant protein were determined. Broiler chickens were subcutaneously immunized with isotonic saline (control), Eimeria recombinant profilin alone, or profilin emulsified with QCDC at 1 and 7 days post-hatch, and orally challenged with live Eimeria acervulina at 7 days following the last immunization. Body weight gains, gut lesion scores, fecal oocyst outputs, profilin serum antibody titers, lymphocyte proliferation, and intestinal cytokine transcript levels were assessed as measures of protective immunity. Chickens immunized with profilin plus QCDC showed increased body weight gains and decreased intestinal lesion scores compared with the profilin only or control groups. However, no differences were found in fecal oocyst shedding among the three groups. Profilin serum antibody titers and antigen-induced peripheral blood lymphocyte proliferation in the profilin/QCDC group were higher compared with the profilin only and control groups. Finally, while immunization with profilin alone or profilin plus QCDC uniformly increased the levels of intestinal transcripts encoding all cytokines examined (IL-1β, IL-10, IL-12, IL-15, IL-17F, and IFN-γ) compared with the control group, transcripts for IL-10 and IL-17F were further increased in the profilin/QCDC group compared with the profilin only group. In summary, this study provides the first evidence of the immunoenhancing activities of QCDC adjuvant in poultry.


title: Displasia ectodérmica anhidrótica asociada a déficit de lectina de unión a manosa

text: Resumen La lectina de unión a la manosa (mannose-binding lectin [MBL]) es una proteína sérica perteneciente al sistema inmunitario innato. Se une a los azúcares de las membranas de múltiples microorganismos, favoreciendo su opsonización y eliminación. El déficit de MBL resulta del polimorfismo del gen MBL2 y se asocia a una amplia variedad de infecciones recurrentes, incluidas las infecciones del tracto respiratorio. Presentamos un caso de displasia ectodérmica anhidrótica asociada a un déficit de MBL, inmunodeficiencia nunca descrita en pacientes afectados de displasia ectodérmica anhidrótica. Abstract Mannose-binding lectin (MBL) is a serum protein of the innate immune system. MBL enhances opsonophagocytosis by binding to carbohydrates expressed by multiple pathogens. MBL deficiency is due to polymorphisms in the structural and promoter sequences of the MBL2 gene and is associated with variety of recurrent infections, including respiratory tract infections. We present a case of anhidrotic ectodermal dysplasia associated with severe mannose-binding lectin deficiency, never described in patients with anhidrotic ectodermal dysplasia.


title: Chloroquine: A Potential Drug in the COVID-19 Scenario

text: Today, the whole world is fighting a public health emergency called ‘COVID-19’ caused by a new infectious virus called SARS-CoV2. Any person can catch COVID-19 from an infected person via aerosol droplets when the person coughs, sneezes, or speaks. To limit such a transmission, World Health Organization (WHO) has recommended people to wear masks and physically distance themselves by staying at least 1 m (3 feet) away from others. As aerosol droplets (by cough or sneeze) land on objects and surfaces around the person such as tables, doorknobs and handrails, and remain active on these surfaces for hours to days, people are advised to use soaps for at least 20 s. and alcohol-based sanitizers as well. As the public made efforts, clinicians and researchers investigated and found that drugs which were initially used to treat other diseases may work as a treatment option for COVID-19. One of those drugs was Chloroquine and its related derivative called hydroxychloroquine. In this review article, we have systematically searched for details of COVID-19 pandemic till May 2020 and assembled few data pertaining to (i) Corona viruses; (ii) SARS-CoV2, the virus that causes COVID-19’ and (iii) How chloroquine and hydroxychloroquine mediates anti-viral effect in both prophylactic and therapeutic setting. These data have been acquired mostly from PubMed and websites of WHO and Indian Council for Medical Research (ICMR). We did a systematic search and found that the properties of chloroquine are very much essential for the COVID-19 scenario. We also bring to you some evidence that the anti-lysosomal activity of chloroquine may be increased by botanicals like betulinic acid.


title: Canine Viral Vaccines at a Turning Point—A Personal Perspective

text: The most important canine viral infections are distemper and CPV-2. Problems of variable CD vaccine safety and efficacy persist, but CD vaccines have greatly reduced the prevalence of disease and cases in vaccinated dogs are now rare. Canine hepatitis (ICH, CAV-1 infection) also has been controlled well by vaccines for more than 35 years and it is now rare; the sporadic cases seen in the 1990s have usually occurred in unvaccinated dogs. CAV-2 vaccines should, therefore, continue to be given since they have proved to be safe and effective, and prevent hepatitis as well as adenoviral tracheobronchitis. Failure to vaccinate would likely result in increase in cases of ICH, a serious disease, but never as significant as distemper and CPV infection. "Are we vaccinating too often?" The question is complex, but the dominant opinion is "yes" (Smith, 1995). The question cannot be responded to unequivocally, however, since manufacturers employ different strains that vary in their immunizing capacity and, probably, duration of immunity. This question was frequent with distemper in the 1960s. At that time, many veterinarians tested batches of the vaccine they used by providing pre- and postvaccinal sera to competent diagnostic laboratories. That practice appeared to benefit veterinarians and dogs, as well as the quality of vaccines. Unfortunately, many owners and some veterinarians seem to hold the view that infectious diseases such as parvovirus infection can be controlled by frequent vaccination alone. The common practice of dog breeders of vaccinating their animals several times each year is senseless. Revaccination for distemper and parvovirus infection is suggested at 1 year of age, but recommendations regarding the frequency of most vaccinations given after that time are unclear. Since most distemper and CPV-2 vaccines probably provide immunity that endures several years, vaccination at 3- to 5-year intervals, after the first year, seems a reasonable practice until more data on duration of immunity become available. "Are too many kinds of vaccines being promoted for dogs?" Distemper and parvovirus vaccines are essential; canine adenovirus vaccines are recommended since the few cases brought to our attention in recent years have been in unvaccinated dogs. Vaccination against respiratory infections is recommended for most dogs, especially those in kennels, or if they are to be boarded. Need has not been clearly established for coronavirus vaccines; Lyme disease vaccines (see below) are useful in preventing illness in areas where the disease exists, but are unnecessary elsewhere since dogs respond rapidly to appropriate antibiotics; current Leptospira bacterins are without benefit since they contain serovars that fail to protect in most areas (noted below). Lyme disease (LD) was not considered here, but newer recombinant (OspA) vaccines are now available that appear to be safe and effective for at least 1 year and they have not caused vaccine-induced postvaccinal lameness, which has been documented with certain whole-cell Lyme disease bacterins. Lyme disease vaccines should be restricted to dogs in, or entering, endemic areas where infested ticks reside. More than 85% of LD cases occur in the mid-Atlantic and Northeastern States, about 10% in six Midwestern states (Michigan, Minnesota, and Wisconsin), and a smaller percentage in restricted areas of northern California and the Pacific Northwest. Leptospirosis also was not discussed here, but vaccines are commonly reported as a cause of anaphylaxis and current vaccines do not contain the serovars prevalent in most regions. The vast majority of cases diagnosed at the New York State Diagnostic Lab at Cornell are grippotyphosa and pomona serovars and there have been no recent cases caused by canicola or icterohemorrhagiae serovars. Because leptospirosis is an important disease of dogs, there is an urgent need for more research and the development of safer vaccines that contain the prevalent


title: Bioluminescence technologies to detect calicivirus protease activity in cell-free system and in infected cells

text: Abstract Feline calicivirus (FCV) is an important veterinary pathogen and causes respiratory disease in cats. Because it grows well in cell culture, FCV is often used as a model virus of non-culturable caliciviruses. In this study, a cell-free and two cell culture-based biosensor assay systems were established to detect FCV protease activity. The assays utilize luciferase sensor technology or second-generation bioluminescence resonance energy transfer (BRET2). A luciferase sensor was designed to contain an FCV protease cleavage motif within the permutated luciferase (GloSensor). The BRET2-based probe contained the same cleavage motif flanked by a renilla luciferase and a variant of green fluorescent protein. To confirm the specificity of these assay systems, GloSensor or a BRET2-based probe containing a mutation in the cleavage motif was also constructed. In a cell-free assay, GloSensor showed increased luminescence in proportion to the amount of FCV protease, while no signal change was observed when the construct harboring the mutant cleavage motif was used. A feline cell line stably expressing GloSensor or the BRET2-based probe was established. Increased levels of GloSensor luminescence, and decreased levels of BRET2 signals were observed according to input FCV titers. In contrast, no significant signal change was observed in the cells stably expressing the mutant cleavage motif. GloSensor and the BRET2-based probe were capable of detecting the inhibitory activity of ribavirin in FCV-infected cells. Our results demonstrate that these biosensors are useful to detect FCV protease activity induced in infected cells, and well worth consideration for screening of anti-FCV protease compounds in cell-free system as well as anti-FCV compounds in cultured cells.


title: Clusters of COVID‐19 in long‐term care hospitals and facilities – Japan, Jan 15‐May 9, 2020

text: AIM: To clarify the association of cluster number and size of coronavirus disease 2019 (COVID‐19) in long‐term care (LTC) hospitals/facilities, general medical/welfare facilities, and non‐medical/welfare facilities, with morbidity and mortality in 47 prefectures during Jan 15 ‐ May 9, 2020 in Japan. METHODS: Information on COVID‐19 clusters (n >2) and morbidity and mortality of COVID‐19 was collected. RESULTS: A total of 381 clusters with 3,786 infected cases were collected, accounting for 23.9% of 15,852 cumulated cases on May 9, 2020. Although the cluster number (/10(7) subjects) in LTC hospitals/facilities was significantly smaller compared to those in the other two groups, the cluster size in LTC hospitals/facilities was significantly larger than that in non‐medical/welfare facilities. Cluster numbers in general medical/welfare facilities and in non‐medical/welfare facilities were significantly positively correlated with morbidity (/10(5)), indicating relatively early identification of clusters in these facilities. Unlike in these facilities, cluster size in LTC hospitals/facilities was significantly positively correlated with morbidity, indicating that clusters in LCT hospitals/facilities were finally identified after already having grown to a large size in areas where infection was prevalent. Multivariate logistic regression analysis revealed that both cluster number and cluster size only in LTC hospitals/facilities were independently associated with higher mortality (> median: 0.64/10(5) subjects) after adjustment. CONCLUSIONS: Preventive efforts against COVID‐19 outbreaks even at the early phase of the epidemic are critically important in LTC hospitals/facilities, since both larger number and size of cluster only in LTC hospitals/facilities were independently linked to higher mortality in prefectures in Japan. <248 words>


title: Techniques used for the discovery of therapeutic compounds: The case of SARS

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS disease, which has ever severely menaced humans from the end of 2002 to June 2003. To date, great efforts have been made for the discovery of therapeutic compounds by using various technologies. In this report, we present a survey of these techniques and their applications in the development of promising anti-SARS agents. Section editors: Li-he Zhang – School of Pharmaceutical Science, Peking University, Beijing, China Kaixian Chen – Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China


title: Cowpea Mosaic Virus

text: Cowpea mosaic virus (CPMV) is the type member of the genus Comovirus, which comprises one of three genera of the family Comoviridae. The genome of CPMV consists of two molecules of positive-strand RNA, which are separately encapsidated in isometric particles consisting of 60 copies each of two types of coat protein. Since its initial isolation, CPMV has been extensively studied from both a genetic and structural point of view and has become a paradigm for plant viruses that express their genome through the synthesis and processing of precursor polyproteins. In this regard, as well as in its particle structure, CPMV resembles other members of the family Picornaviridae. More recently, the virus has been used for a number of biotechnological applications.


title: Human metapneumovirus infection: Diagnostic impact of radiologic imaging

text: BACKGROUND: Human metapneumovirus (hMPV) is a recently detected virus, which can cause mild to severe respiratory tract infections. Through this study, we aimed to detail the outcomes of hMPV infections. MATERIALS/METHODS: Between January 2012 and November 2017, patients who had hMPV detected in nasopharyngeal or bronchoalveolar lavage by molecular respiratory pathogen tests were evaluated. The Food and Drug Administration cleared multiplexed‐polymerase chain reaction system (Idaho Technology, Salt Lake City, UT) was used for diagnosis. Chest radiography (CR) and computed tomography (CT) were evaluated by an expert radiologist. RESULTS: In total 100 patients were included, the mean age was 22.9 (0‐87) years, and 50% were male. The hospitalization rate was 52%. Lower respiratory system infection (LRTI) was diagnosed in 44 patients with clinical findings, and in 31 patients out of 44 the radiological findings supported the diagnosis. The LRTI rate was significantly higher in adults than children (66.7%‐32.8%; P = 0.001). In CR, peribronchovascular infiltration (PI) was the most common feature seen in 14 out of 18 patients and was generally bilateral (13 out of 18 patients). In CT imaging, ground‐glass opacity was the most common finding seen in 11 out of 16 patients and nodular consolidation in five patients. Ribavirin was given to four patients, three of whom were severe and required respiratory support. None of the patients died of hMPV infection. CONCLUSIONS: The ground‐glass opacity in CT was similar to other respiratory virus infections, and PI in CR was very common and typical; however, nodular consolidation that may mimic bacterial infection was seen in one‐fourth of CT.


COVID-19 and oral radiology


Algunas lecciones aprendidas (o no tanto) del COVID-19


title: Medicinal plants of the genus Betula—Traditional uses and a phytochemical–pharmacological review

text: Abstract Ethnopharmacological relevance Trees and shrubs of the genus Betula (Betulaceae) inhabit various ecosystems in temperate and boreal climate zones of the northern hemisphere. The healing properties of Betula bark and bark extracts have been known for a long time in traditional medicine in different parts of the world. Several species of Betula have traditionally been used for the treatment of various inflammatory diseases including arthritis. The purpose of this review is to provide updated, comprehensive and categorized information on the botany, traditional uses, phytochemistry and pharmacological and toxicological research of Betula species in order to explore their therapeutic potential and evaluate future research opportunities. Materials and methods All the available information on various species belonging to the genus Betula was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar, JCCC@INSTIRC and Web of Science) and a library search for articles published in peer-reviewed journals. Results Although over a hundred Betula species are found distributed globally, about 7 different species of Betula have been documented for their traditional uses. Phytochemical research on Betula species has led to the isolation of triterpenoids, diarylheptanoids, phenylbutanoids, lignans, phenolics and flavonoids. Crude extracts, fractions and phytochemical constituents isolated from Betula showed a wide spectrum of in vitro and in vivo pharmacological activities like immunomodulatory, anti-inflammatory, antimicrobial, antiviral, antioxidant, antidiabetic, dermatological, gastroprotective and hepatoprotective. Antiarthritic and anticancer are the two major areas of research conducted on these species. The anti-carcinogenic effects of Betula bark, betulin as well as betulinic acid have been extensively studied. Conclusions Several species belonging to the genus Betula are widely used in traditional medicine. Betula platyphylla and Betula pendula have specifically been found to be potentially useful in the treatment of degenerative joint disease. There is convincing evidence in experimental animal models in support of their anti-carcinogenic effects. However, it would be worthwhile to investigate the biochemical and physiological mechanisms as well as detailed preclinical toxicity, bioavailability, pharmacokinetics and pharmacodynamics of the different biologically active extracts as well as molecules in sufficient detail. An integrated and holistic approach is required for tapping the full potentials of this important genus.


title: A mechanism-based parameterisation scheme to investigate the association between transmission rate of COVID-19 and meteorological factors on plains in China

text: The novel coronavirus disease 2019 (COVID-19), which first emerged in Hubei province, China, has become a pandemic. However, data regarding the effects of meteorological factors on its transmission are limited and inconsistent. A mechanism-based parameterisation scheme was developed to investigate the association between the scaled transmission rate (STR) of COVID-19 and the meteorological parameters in 20 provinces/municipalities located on the plains in China. We obtained information on the scale of population migrated from Wuhan, the world epicentre of the COVID-19 outbreak, into the study provinces/municipalities using mobile-phone positioning system and big data techniques. The highest STRs were found in densely populated metropolitan areas and in cold provinces located in north-eastern China. Population density had a non-linear relationship with disease spread (linearity index, 0.9). Among various meteorological factors, only temperature was significantly associated with the STR after controlling for the effect of population density. A negative and exponential relationship was identified between the transmission rate and the temperature (correlation coefficient, −0.56; 99% confidence level). The STR increased substantially as the temperature in north-eastern China decreased below 0 °C (the STR ranged from 3.5 to 12.3 when the temperature was between −9.41 °C and −13.87 °C), whilst the STR showed less temperature dependence in the study areas with temperate weather conditions (the STR was 1.21 ± 0.57 when the temperature was above 0 °C). Therefore, a higher population density was linearly whereas a lower temperature (<0 °C) was exponentially associated with an increased transmission rate of COVID-19. These findings suggest that the mitigation of COVID-19 spread in densely populated and/or cold regions will be a great challenge.


title: Outpatient management of kidney transplant recipients with suspected COVID‐19—Single‐center experience during the New York City surge

text: Data describing the clinical progression of coronavirus disease 2019 (COVID‐19) in transplant recipients are limited. In New York City during the surge in COVID‐19 cases, a systematic approach to monitoring and triaging immunocompromised transplant patients was required in the context of strained healthcare resources, limited outpatient testing, and heightened hospital exposure risks. Public health guidance at the onset of the COVID‐19 outbreak recommended outpatient monitoring of mildly symptomatic patients without specific recommendations for special populations such as transplant recipients. We developed and implemented a systematic monitoring algorithm for kidney transplant recipients at our transplant center who reported mild symptoms suggestive of COVID‐19. We describe the outcomes of the first 44 patients monitored through this algorithm. A total of 44 kidney transplant recipients thought to be symptomatic for COVID‐19 disease were followed for a minimum of 14 days. The majority of mildly symptomatic patients (34/44) had clinical progression of disease and were referred to the emergency department where they all tested PCR positive and required hospitalization. More than half of these patients presented with hypoxia requiring supplemental oxygen, 39% were intubated within 48 hours, and 53% developed acute kidney injury but did not require dialysis. There were 6 deaths. During surge outbreaks, kidney transplant patients with even mild symptoms have a high likelihood of COVID‐19 disease and most will worsen requiring hospitalization for supportive measures. Earlier outpatient testing and hospitalization may improve COVID‐19 outcomes among transplant recipients.


title: An emerging cyberinfrastructure for biodefense pathogen and pathogen–host data

text: The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host–pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.


title: pknotsRG: RNA pseudoknot folding including near-optimal structures and sliding windows

text: RNA pseudoknots are an important structural feature of RNAs, but often neglected in computer predictions for reasons of efficiency. Here, we present the pknotsRG Web Server for single sequence RNA secondary structure prediction including pseudoknots. pknotsRG employs the newest Turner energy rules for finding the structure of minimal free energy. The algorithm has been improved in several ways recently. First, it has been reimplemented in the C programming language, resulting in a 60-fold increase in speed. Second, all suboptimal foldings up to a user-defined threshold can be enumerated. For large scale analysis, a fast sliding window mode is available. Further improvements of the Web Server are a new output visualization using the PseudoViewer Web Service or RNAmovies for a movie like animation of several suboptimal foldings. The tool is available as source code, binary executable, online tool or as Web Service. The latter alternative allows for an easy integration into bio-informatics pipelines. pknotsRG is available at the Bielefeld Bioinformatics Server (http://bibiserv.techfak.uni-bielefeld.de/pknotsrg).


title: The Lectin ERGIC-53 Goes Viral

text: The biosynthesis of fusion-competent envelope glycoproteins (GPs) is a crucial step in productive viral infection. In this issue, Klaus et al. (2013) identify the cargo receptor endoplasmic reticulum (ER)-Golgi intermediate compartment 53 kDa protein (ERGIC-53) as a binding partner for viral GPs and a crucial cellular factor required for infectious virus production.


title: Tracing New Clinical Manifestations in Patients with COVID-19 in Chile and Its Potential Relationship with the SARS-CoV-2 Divergence

text: PURPOSE OF REVIEW: In this review, we discuss the current implications of the changing genomic epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), etiological agent of the Coronavirus Disease 2019 (COVID-19) and its potential relationship with the change of clinical manifestations in patients with confirmed infection. RECENT FINDINGS: Over the course of the current pandemic, the virus has been found more diverse in new countries. Simultaneously, also new clinical manifestations are observed, particularly more prominent gastrointestinal and neurological findings. SUMMARY: SARS-CoV-2/COVID-19 is changing not only its epidemiology, but also its genomic diversity and clinical manifestations, both aspects coupled, needs to be considered in the study of this ongoing pandemic.


title: Optimizing Anti-Viral Vaccine Responses: Input from a Non-Specialist

text: Recently, the research community has had a real-world look at reasons for improving vaccine responses to emerging RNA viruses. Here, a vaccine non-specialist suggests how this might be done. I propose two alternative options and compare the primary alternative option with current practice. The basis of comparison is feasibility in achieving what we need: a safe, mass-produced, emerging virus-targeted vaccine on 2–4 week notice. The primary option is the following. (1) Start with a platform based on live viruses that infect bacteria, but not humans (bacteriophages, or phages). (2) Isolate phages (to be called pathogen homologs) that resemble and provide antigenic context for membrane-covered, pathogenic RNA viruses; coronavirus-phage homologs will probably be found if the search is correctly done. (3) Upon isolating a viral pathogen, evolve its phage homolog to bind antibodies neutralizing for the viral pathogen. Vaccinate with the evolved phage homolog by generating a local, non-hazardous infection with the phage host and then curing the infection by propagating the phage in the artificially infecting bacterial host. I discuss how this alternative option has the potential to provide what is needed after appropriate platforms are built.


title: Targeting the porcine immune system—Particulate vaccines in the 21st century

text: During the last decade, the propagation of immunological knowledge describing the critical role of dendritic cells (DC) in the induction of efficacious immune responses has promoted research and development of vaccines systematically targeting DC. Based on the promise for the rational design of vaccine platforms, the current review will provide an update on particle-based vaccines of both viral and synthetic origin, giving examples of recombinant virus carriers such as adenoviruses and biodegradable particulate carriers. The viral carriers carry pathogen-associated molecular patterns (PAMP), used by the original virus for targeting DC, and are particularly efficient and versatile gene delivery vectors. Efforts in the field of synthetic vaccine carriers are focussing on decorating the particle surface with ligands for DC receptors such as heparan sulphate glycosaminoglycan structures, integrins, Siglecs, galectins, C-type lectins and toll-like receptors. The emphasis of this review will be placed on targeting the porcine immune system, but reference will be made to advances with murine and human vaccine delivery systems where information on DC targeting is available.


title: First molecular identification of kobuviruses in wolves (Canis lupus) in Italy

text: Canine kobuviruses (CaKoVs) were first identified in diarrhoeic and asymptomatic dogs in 2011 in the USA. Subsequent studies have demonstrated a worldwide distribution of these viruses, but it is not clear if CaKoVs play a role as enteric pathogens of dogs. More recently, CaKoV RNA has been detected in wild carnivores, including red fox, golden jackal, side-striped jackal and spotted hyena. In this study, we addressed the hypothesis that wolves are susceptible to CaKoV infections. A total of 185 wolf stool samples were collected from necropsied animals and from transects in the Liguria, Piemonte and Valle D’Aosta regions of Italy, and CaKoV RNA was identified in two of these specimens. Both samples were obtained from necropsied wolves, with a prevalence rate of 4.9% (2/41). Sequence analysis of the full-length VP1 region showed that these strains displayed the highest nucleotide (nt) sequence identity (86.3-98.5%) to canine strains identified in the UK and Africa, and to kobuviruses that were previously detected in other African wild carnivores. This suggests that genetically related CaKoV strains circulate in domestic and wild carnivores, with interspecies transmission being not uncommon among carnivores of different ecosystems.


title: Up-Regulation of Hepatitis C Virus Replication and Production by Inhibition of MEK/ERK Signaling

text: BACKGROUND: Viruses interact with and exploit the host cellular machinery for their multiplication and propagation. The MEK/ERK signaling pathway positively regulates replication of many RNA viruses. However, whether and how this signaling pathway affects hepatitis C virus (HCV) replication and production is not well understood. METHODS AND RESULTS: In this study, we took advantage of two well-characterized MEK/ERK inhibitors and MEK/ERK dominant negative mutants and investigated the roles of the MEK/ERK signaling pathway in HCV gene expression and replication. We showed that inhibition of MEK/ERK signaling enhanced HCV gene expression, plus- and minus-strand RNA synthesis, and virus production. In addition, we showed that this enhancement was independent of interferon-α (IFN-α) antiviral activity and did not require prior activation of the MEK/ERK signaling pathway. Furthermore, we showed that only MEK and ERK-2 but not ERK-1 was involved in HCV replication, likely through regulation of HCV RNA translation. CONCLUSIONS: Taken together, these results demonstrate a negative regulatory role of the MEK/ERK signaling pathway in HCV replication and suggest a potential risk in targeting this signaling pathway to treat and prevent neoplastic transformation of HCV-infected liver cells.


title: COVID-19 and telemedicine: Immediate action required for maintaining healthcare providers well-being

text: Abstract The well-being of the health care workforce is the cornerstone of every well-functioning health system. As a result of the pandemic, medical healthcare providers are under an enormous amount of workload pressure along with increased total health expenditures. The overwhelming burden of COVID-19 illness could lead to caregiver burnout. Direct-to-consumer telemedicine can enable patients to connect with their healthcare provider at a distance. This virtual platform could be used by smartphones or webcam-enabled computers and allows physicians to effectively screen patients with early signs of COVID-19 before they reach to hospital.


title: Complete Genome Sequence of SARS-CoV-2 in a Tiger from a U.S. Zoological Collection

text: This report describes the identification and characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a Malayan tiger in a U.S. zoo.


title: Understanding COVID-19 transmission through Bayesian probabilistic modeling and GIS-based Voronoi approach: a policy perspective

text: Originating from Wuhan, China, COVID-19 is spreading rapidly throughout the world. The transmission rate is reported to be high for this novel strain of coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as compared to its predecessors. Major strategies in terms of clinical trials of medicines and vaccines, social distancing, use of personal protective equipment (PPE), and so on are being implemented in order to control the spread. The current study concentrates on lockdown and social distancing policy followed by the Indian Government and evaluates its effectiveness using Bayesian probability model (BPM). The change point analysis (CPA) done through the above approach suggests that the states which implemented the lockdown before the exponential rise of cases are able to control the spread of the disease in a much better and efficient way. The analysis has been done for states of Maharashtra, Gujarat, Madhya Pradesh, Rajasthan, Tamil Nadu, West Bengal, Uttar Pradesh, and Delhi as union territory. The highest value of Δ (delta) is reported for Gujarat and Madhya Pradesh with a value of 9.6 weeks, while the lowest value is 4.7, evidently for Maharashtra which is the worst affected. All of the states indicate a significant correlation (p < 0.05, tstat > tcritical) for Δ, i.e., the difference in the time period of CPA and lockdown with cases per population (CPP) and cases per unit area (CPUA), while weak correlation (p < 0.1 and tstat < tcritical) is exhibited by delta and cases per unit population density (CPD). For both CPP and CPUA, tstat > tcritical indicating a significant correlation, while Pearson’s correlation indicates the direction to be negative. Further analysis in terms of identification of high-risk areas has been studied from the Voronoi approach of GIS based on the inputs from BPM. All the states follow the above pattern of high population, high case scenario, and the boundaries of risk zones can be identified by Thiessen polygon (TP) constructed therein. The findings of the study help draw strategic and policy-driven response for India, toward tackling COVID-19 pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10668-020-00849-0) contains supplementary material, which is available to authorized users.


title: Use of Peptides for the Management of Alzheimer’s Disease: Diagnosis and Inhibition

text: Alzheimer’s disease (AD) is a form of dementia and the most common progressive neurodegenerative disease (ND). The targeting of amyloid-beta (Aβ) aggregation is one of the most widely used strategies to manage AD, and efforts are being made globally to develop peptide-based compounds for the early diagnosis and treatment of AD. Here, we briefly discuss the use of peptide-based compounds for the early diagnosis and treatment of AD and the use of peptide-based inhibitors targeting various Aβ aggregation checkpoints. In addition, we briefly discuss recent applications of peptide-based inhibitors against various AD targets including amyloid beta, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tyrosine phosphatase (TP) and potassium channel KV1.3.


title: Using the Electronic Medical Record to Correlate Kawasaki Disease Phenotypes With Clinical Outcomes

text: BACKGROUND: We sought to systematically standardize the documentation of clinical and laboratory features in Kawasaki disease (KD) on the day of initial treatment and correlate the presentation with clinical outcomes. METHODS: Kawasaki disease features and classification were documented by the attending physician using a standardized documentation tool on the day of treatment for KD, including confidence in the KD diagnosis on a 4-point scale. Incomplete KD was further classified using American Heart Association (AHA) criteria (sufficient or insufficient) and baseline echocardiogram data. We prospectively recorded intravenous immunoglobulin (IVIG) resistance, coronary artery abnormalities (CAAs), periungual peeling, and retrospectively identified subsequent diagnoses of autoimmune/inflammatory disease. RESULTS: From November 2012 to October, 2015, 162 patients were treated for KD: 105 with complete KD (Group 1), 7 with incomplete KD based on CAAs on day of KD diagnosis (Group 2), 23 with incomplete KD meeting AHA criteria (Group 3), and 27 with incomplete KD and insufficient AHA criteria (Group 4). Group 4 patients had lower baseline median C-reactive protein levels (Group 4 median 4.65 mg/dL [interquartile range {IQR}, 2.3–13.6] vs Group 1 median 8.0 mg/dL [IQR, 4.5–17], Group 2 median 13.9 mg/dL [IQR, 1.4–18.2], Group 3 median 13.3 mg/dL [IQR, 4.9–20.2]), and no coronary abnormalities developed, although 11% had IVIG resistance. Group 4 had higher rates of subsequent autoimmune/inflammatory conditions diagnosed (11.1% in Group 4 vs <5% for all others, P = .02). CONCLUSIONS: Standardized documentation and classification of KD features may be useful to correlate with clinical outcomes, including subsequent diagnosis of autoimmune/autoinflammatory disease. Among patients with incomplete KD who did not meet AHA criteria and had a normal baseline echocardiogram, the IVIG resistance rate may have been related to a lower likelihood of an accurate diagnosis of KD.


title: Widening Disparities Among Patients with Rheumatic Diseases in the COVID‐19 Era: An Urgent Call to Action

text: Recent data from multiple public health departments across the U.S. highlighting the disproportionate burden of COVID‐19 infections in vulnerable populations serve as an urgent call to action. As rheumatologists, we are acutely aware of the higher morbidity and mortality, and for a number of our diseases, the higher incidence and prevalence among racial/ethnic minorities and individuals of lower socioeconomic status (SES). Comorbidities are frequent, timely access to subspecialty care is limited, receipt of high quality care is less common, and care is more often fragmented with frequent, avoidable acute care use.


Outbreak of Middle East Respiratory Syndrome in Korea?


title: Analyzing COVID-19 pandemic for unequal distribution of tests, identified cases, deaths, and fatality rates in the top 18 countries

text: BACKGROUND AND AIMS: COVID-19 pandemic has affected various countries differently due to variance in demographics, income level, health infrastructure, government response, control and enforcement, and cultural traits of different populations. This study aims to identify significant factors behind the unequal distribution of identified cases and deaths in different countries. Our study’s objective is comparative analysis and identification of relations between the spread of COVID-19 pandemic, population characteristics, and government response. METHODS: The top 18 countries worst hit by COVID-19 cases were identified. The data metrics, such as the number of cases, deaths, fatality rates, tests, average life expectancy, and population, were collected and consolidated. RESULTS: Countries with significant percentage of the older population are vulnerable to a high number of deaths due to COVID-19. Developed countries have higher per capita testing, whereas testing is less intensive in developing/underdeveloped countries. There is a consensus among health experts that COVID-19 has higher fatality rates for people above 60, however, with further age, this increases exponentially. Countries with higher life expectancy are also high-income countries, and the best course of action would be to provide specialized support to self-isolate for people of ages 75 and above. CONCLUSION: The behaviour of disease occurring at a large scale and interaction with different populations is studied to understand and differentiate the factors and measures that successfully inhibited the pandemic. The study benchmarks different countries based on their performance and efforts against the pandemic and provides some useful insights on the efficiency of their governance and potential to improve & ramp up their programs. The economic status and existing healthcare infrastructure as they are the key factors in determining the country’s ability to contain and minimize the losses from this pandemic.


title: Analysis of Outbreak and Global Impacts of the COVID-19

text: Corona viruses are a large family of viruses that are not only restricted to causing illness in humans but also affect animals such as camels, cattle, cats, and bats, thus affecting a large group of living species The outbreak of Corona virus in late December 2019 (also known as COVID-19) raised major concerns when the outbreak started getting tremendous While the first case was discovered in Wuhan, China, it did not take long for the disease to travel across the globe and infect every continent (except Antarctica), killing thousands of people Since it has become a global concern, different countries have been working toward the treatment and generation of vaccine, leading to different speculations While some argue that the vaccine may only be a few weeks away, others believe that it may take some time to create the vaccine Given the increasing number of deaths, the COVID-19 has caused havoc worldwide and is a matter of serious concern Thus, there is a need to study how the disease has been propagating across continents by numbers as well as by regions This study incorporates a detailed description of how the COVID-19 outbreak started in China and managed to spread across the globe rapidly We take into account the COVID-19 outbreak cases (confirmed, recovered, death) in order to make some observations regarding the pandemic Given the detailed description of the outbreak, this study would be beneficial to certain industries that may be affected by the outbreak in order to take timely precautionary measures in the future Further, the study lists some industries that have witnessed the impact of the COVID-19 outbreak on a global scale


title: The effect of urbanization on carbon dioxide emissions efficiency in the Yangtze River Delta, China

text: Abstract Cities have been one of the most important areas of CO2 emissions. It is increasingly important to research the effect of urbanization on CO2 emissions, especially in large emerging and developing economies, due to the indispensable need for understanding the effect of urbanization on CO2 emissions, evaluating carbon reduction tasks and providing the scientific basis for low-carbon urbanization. Utilizing a balanced panel dataset in the Yangtze River Delta (YRD), China, during the period of 2000–2010, this paper employed data envelopment analysis (DEA) window analysis and a spatial lag panel Tobit model to investigate the effect of urbanization on CO2 emissions efficiency (the ratio of the target CO2 emissions to the actual CO2 emissions). The results show that the average CO2 emissions efficiency was 0.959 in 2010, and CO2 emissions efficiency ranged from 0.816 to 1 and exhibited spatial clustering in the region. The larger potential of CO2 emissions reduction appeared in Zhenjiang and Yangzhou, indicating that more CO2 emissions reduction tasks should be allocated to these two cities. Urbanization has negative effects on improving CO2 emissions efficiency, and there is a U-curve relation between CO2 emissions efficiency and urbanization, indicating that CO2 emissions efficiency decreases at the early stage of urbanization, then increases when urbanization reach a high level. There is spatial spillover effect among the prefecture-level cities, suggesting that different prefecture-level governments should coordinate with each other to improve CO2 emissions efficiency in the whole area. Gross domestic product (GDP) per capita also plays a markedly positive role in improving CO2 emissions efficiency. This research highlights the effect of urbanization on CO2 emissions efficiency and the importance of improving CO2 emissions efficiency in developing countries.


title: Acute systemic DNA damage in youth does not impair immune defense with aging

text: Aging‐related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age‐related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole‐body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/6 mice to sublethal WBI (0.5–4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock‐irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T‐ and B‐cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model.


title: The pandemic influenza planning process in Ontario acute care hospitals

text: BACKGROUND: There will be little time to prepare when an influenza pandemic strikes; hospitals need to develop and test pandemic influenza plans beforehand. METHODS: Acute care hospitals in Ontario were surveyed regarding their pandemic influenza preparedness plans. RESULTS: The response rate was 78.5%, and 95 of 121 hospitals participated. Three quarters (76.8%, 73 of 95) of hospitals had pandemic influenza plans. Only 16.4% (12 of 73) of hospitals with plans had tested them. Larger (χ(2) = 6.7, P = .01) and urban hospitals (χ(2) = 5.0, P = .03) were more likely to have tested their plans. 70.4% (50 of 71) Of respondents thought the pandemic influenza planning process was not adequately funded. No respondents were “very satisfied” with the completeness of their hospital's pandemic plan, and only 18.3% were “satisfied.” CONCLUSION: Important challenges were identified in pandemic planning: one quarter of hospitals did not have a plan, few plans were tested, key players were not involved, plans were frequently incomplete, funding was inadequate, and small and rural hospitals were especially disadvantaged. If these problems are not addressed, the result may be increased morbidity and mortality when a virulent influenza pandemic hits.


title: Addressing male sexual and reproductive health in the wake of COVID-19 outbreak

text: PURPOSE: The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a “cytokine storm”, which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. METHODS: A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. RESULTS: Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. CONCLUSION: COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.


Face à la COVID-19, vaccinons contre la grippe !


title: Optimal management of acute kidney injury in critically ill patients with invasive fungal infections being treated with liposomal amphotericin B

text: Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully used in the setting of AKI. The first was Aspergillus infection in a 63-year-old man with bleeding oesophageal varices related to advanced liver disease. The second was gastrointestinal mucormycosis in a 74-year-old man who developed a small bowel obstruction following an autologous stem cell transplant for mantle cell lymphoma. The third was a Fusarium infection in a 32-year-old woman on immunosuppression for a bilateral lung transplant for cystic fibrosis. In all three cases, liposomal amphotericin B was required for urgent management of the patient’s IFI. We discuss the rationale for treatment with a potentially nephrotoxic agent in this setting.


ZIMBABWE: UN Launches Virus Aid Plan