title: Knowledge and attitude of healthcare workers about middle east respiratory syndrome in multispecialty hospitals of Qassim, Saudi Arabia

text: BACKGROUND: With the increase in prevalence of Middle East Respiratory Syndrome (MERS), healthcare workers (HCWs) are at risk of acquiring and subsequently transmitting this lethal virus. In view of this, HCWs were evaluated for their knowledge of and attitude towards MERS in Saudi Arabia. METHODS: A cross sectional study was performed in two hospitals of Qassim region in Saudi Arabia. A total of 280 healthcare workers were selected to participate in this study. Knowledge and attitude were assessed by using self-administered and pretested questionnaire. Descriptive statistics were carried out to express participants’ demographic information, mean knowledge score and mean attitude score of HCWs. Inferential statistics (Mann–Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Chi squares tests were used to assess the association between study variables and attitude questions. Spearman’s rho correlation was used to identify the association between the knowledge, attitude scores. RESULT: Participants demonstrated good knowledge and positive attitude towards MERS. The mean scores of knowledge and attitude were 9.45 ± 1.69 (based on 13 knowledge questions) and 1.82 ± 0.72 (based on 7 attitude questions). The correlation between knowledge and attitude was significant (correlation coefficient: 0.12; P <0.001). HCWs were less educated about the management (42.4%), source (66%) and consequences of MERS (67.3%), while a majority of them were well aware of the hallmark symptoms (96%), precautionary measures (96%) and hygiene issues (94%). Although the majority of respondents showed positive attitude towards the use of protective measures (1.52 ± 0.84), their attitude was negative towards their active participation in infection control program (2.03 ± 0.97). Gender and experience were significantly associated with knowledge and attitude (P < 0.05). CONCLUSIONS: The findings of this study showed that healthcare workers in Qassim region of Saudi Arabia have good knowledge and positive attitude towards MERS. Yet there are areas where low knowledge and negative attitude of HCWs was observed. However, studies are required to assess the knowledge and attitude of HCWs at national level so that effective interventions could be designed as surveillance and infection control measures are critical to global public health.


title: Pattern formation in multiplex networks

text: The advances in understanding complex networks have generated increasing interest in dynamical processes occurring on them. Pattern formation in activator-inhibitor systems has been studied in networks, revealing differences from the classical continuous media. Here we study pattern formation in a new framework, namely multiplex networks. These are systems where activator and inhibitor species occupy separate nodes in different layers. Species react across layers but diffuse only within their own layer of distinct network topology. This multiplicity generates heterogeneous patterns with significant differences from those observed in single-layer networks. Remarkably, diffusion-induced instability can occur even if the two species have the same mobility rates; condition which can never destabilize single-layer networks. The instability condition is revealed using perturbation theory and expressed by a combination of degrees in the different layers. Our theory demonstrates that the existence of such topology-driven instabilities is generic in multiplex networks, providing a new mechanism of pattern formation.


title: Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012–2015

text: Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1–4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3–5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.


Canakinumab in a subgroup of patients with COVID-19


title: Management of Allergic Patients During the COVID-19 Pandemic in Asia

text: Although a viral infection is a major triggering factor of asthma and allergic diseases, asthma is suggested to be not a predisposing condition for coronavirus disease 2019 (COVID-19) infection However, patients with severe asthma/allergic disease requiring systemic corticosteroids or immunosuppressive agents may be at higher risk of more severe clinical course of this infectious disease For allergic patients who have been followed up at an allergy clinic in our region, it is recommended that they (patients with asthma, rhinitis, atopic dermatitis or chronic urticaria) continue to receive maintenance therapy and be in a well-controlled status Patients who have used biologics (currently available for targeting type 2 inflammation) and allergen immunotherapy should continue the treatment while minimizing hospital and face-to-face visits It is essential to wear protective equipment for the protection of health care workers as well as patients We report this consensus to support allergists and clinical immunologists to make optimal decisions under the urgent situation in Asia


title: Quantification of individual subgenomic mRNA species during replication of the coronavirus transmissible gastroenteritis virus

text: Abstract A biotinylated-oligonucleotide-based method was used to isolate the subgenomic mRNAs of the coronavirus transmissible gastroenteritis virus (TGEV) to investigate the amounts of the mRNAs produced at early, middle and late times in the replication cycle. TGEV mRNA 6, which encodes the N protein, was observed to be the most abundant species throughout the replication cycle. The ratios of mRNA 6 to the other mRNAs were 1:0.11 (mRNA 2), 1:0.16 (mRNAs 3 and 4) and 1:0.37 (mRNA 5) at 12 h post-infection. All the mRNA species were differentially regulated throughout the replication cycle, although the rate of accumulation of mRNAs 4, 5, and 6, but not mRNA 3, increased markedly towards the end of the replication cycle. mRNA 7 was not detected in the system used. There was no observable correlation between the amounts of each mRNA synthesised and the potential degree of base pairing between the 3′ end of the leader sequence and the transcription associated sequences on the genomic RNA at any time during the replication cycle. This indicates that the extent of base pairing was not the only factor involved in the control of subgenomic mRNA synthesis.


title: In vitro mitogen responses and lymphocyte subpopulations in cheetahs

text: Abstract Lack of genetic variability and apparent susceptibility of cheetahs (Acinonyx jubatus) to coronavirus infection has lead to speculation that this species may have immune system deficits. To establish a foundation for evaluation of the immune function, cheetah peripheral blood mononuclear cells (PBM) were stimulated by a panel of six mitogens, and responses compared with those of domestic cat PBM. Individual responses in both species were variable, but evenly distributed throughout the range of stimulation for each mitogen. Proliferation by PBM from domestic cats occured within the same range as that of the cheetahs. However, a significantly lower response to peanut agglutinin (PNA) was observed with domestic cat PBM. Although responses varied between animals, certain individual cheetahs were consistent responders. The decreased values could not be explained by lack of IL-2 responsiveness since exogenous IL-2 significantly enhanced mitogen-stimulated proliferation in 11 of 12 cheetahs tested. The phenotypic distribution of domestic cat and cheetah lymphocyte subpopulations was similar as assessed by immunofluorescence staining for surface immunoglobulin (sIg) and cytotoxic T (Tc) cells (using a specific monoclonal antibody, FT2). Values for B cells (31.2% sIg+) and Tc (28.7% FT2 +) were slightly higher in domestic cats as compared with cheetah PBM (13.3% sIg+; 19.0% FT2+). Even though no species-specific deficits were detected, a significant negative correlation between PHA-stimulated proliferation and percent FT2+ (Tc) cheetah cells was observed. This indicates that proliferation can be used indirectly to assess relative numbers of functional T helper cells in cheetahs. Our studies suggest that these aspects of the cheetah's immune system are comparable with the domestic cat, and establish a basis for in vitro assays evaluating antigen-specific responses.


title: Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

text: Abstract Objective to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever. Methods cross‐sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real‐time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test). Results 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co‐detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths. Conclusions the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co‐detection was frequent in patients with cancer and ARIs. Resumo Objetivo estimar a prevalência da infecção pelos vírus respiratórios em pacientes pediátricos com câncer e infecção respiratória aguda (IRA) e/ou febre. Métodos estudo transversal, de janeiro de 2011 a dezembro de 2012. Foram analisadas secreções de aspirado da nasofaringe de menores de 21 anos, com quadro respiratório agudo, atendidos nos hospitais Grendacc e HU, Jundiaí, SP. Foi aplicado o teste rápido para detecção dos vírus influenza (Kit Biotrin®) e a reação em cadeia da polimerase multiplex em tempo real (Kit multiplex/Fast Trade®) para detecção dos vírus: influenza (A, H1N1, B), rinovírus, parainfluenza, adenovírus respiratório, vírus respiratório sincicial, parechovírus, bocavírus, metapneumovírus humano e coronavírus humano. Foi estimada a prevalência de infecção viral e usados testes de associação (χ2 ou teste exato de Fisher). Resultados foram analisadas 104 amostras de aspirado de nasofaringe e sangue. A mediana para a idade foi 12±5,2 anos; masculino (51%); cor branca (68%); IVAS de repetição (32%); uso prévio de antibiótico (32%); tosse (19,8%); e contato com IVAS (8%). Apresentavam‐se em bom estado geral 94,3% dos pacientes. A leucemia linfocítica aguda (42,3%) foi mais prevalente. Foram detectados vírus respiratórios em 50% das amostras: rinovírus (23,1%), vírus sincicial respiratório A/B (8,7%) e coronavírus (6,8%). Ocorreu codetecção em 19% entre dois vírus, e de 3% entre três vírus, sendo a mais frequente entre rinovírus e coronavírus 43. Febre em neutropênicos foi de 13%, sendo quatro (30,7%) com vírus positivo. Não houve óbitos. Conclusões a prevalência de vírus respiratórios foi importante no episódio infeccioso, sem aumento da morbimortalidade. As codetecções foram frequentes em pacientes com câncer e IRA.


title: Community-Acquired Pneumonia

text: Community-acquired pneumonia is one of the most common infections seen in emergency department patients. There is a wide spectrum of disease severity and viral pathogens are common. After a careful history and physical examination, chest radiographs may be the only diagnostic test required. The first step in management is risk stratification, using a validated clinical decision rule and serum lactate, followed by early antibiotics and fluid resuscitation when indicated. Antibiotics should be selected with attention to risk factors for multidrug-resistant respiratory pathogens. Broad use of pneumococcal vaccine in adults and children can prevent severe community-acquired pneumonia.


title: Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy

text: Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease.


COVID-19 pandemic and the burn survivor community: A call for action


title: State feedback impulsive therapy to SIS model of animal infectious diseases

text: Abstract Controlling animal infectious diseases and its related infra microbes is of great significance to public health, since a lot of infectious diseases originate from animal epidemics and they often threaten human health. A state feedback impulsive model is constructed to depict the transmission and treatment of animal epidemics. Basing on the impulsive model, the existence of order-1 periodic solution and its stability are proved with a novel method. The theoretical results indicate that the impulsive treatment triggered by the number of infectious is an efficient approach to control animal infectious disease from breakout. Numerical simulation is presented to support the theoretical conclusion in the end.


title: Personal Protective Equipment: Protecting Health Care Providers in an Ebola Outbreak

text: Abstract Purpose The recent Ebola epidemic that devastated West Africa has infected and killed more health care providers than any other outbreak in the history of this virus. An improved understanding of pathogen transmission and the institution of strategies to protect health care providers against infection are needed in infectious disease outbreaks. This review connects what is known about Ebola virus transmission with personal protective equipment (PPE) designed to arrest nosocomial transmission. Methods Articles pertaining to filovirus transmission and PPE in filovirus outbreaks were reviewed and findings are presented. In addition, studies that evaluated PPE and donning and doffing strategies are presented. Findings PPE is one step in a comprehensive infection prevention and control strategy that is required to protect health care providers. Given that the Ebola virus is primarily transmitted through direct contact of mucous membranes and cuts in the skin with infected patients and/or their bodily fluids, it is necessary to cover these potential portals of infection with PPE as part of a structured and instructed donning and doffing procedure. Implications Current recommendations about PPE and the donning and doffing processes are based on anecdotal experience. However, the use of non-human viruses can help provide evidence-based guidelines on both PPE and donning and doffing processes.


title: Irradiation and Consumers Acceptance

text: Treatment of foods with irradiation is an effective means to prevent food-borne diseases which cause massive disruptions to the health and economic systems of societies. Although the safety of irradiation technology to process foods has been extensively proven and it is highly regulated, some consumers are still reluctant to accept irradiated foods. The lack of access to science-based knowledge coupled with actions from consumer groups and the need for labeling hamper the commercial success of irradiated foods that are safe and nutritious. This article provides an overview of how consumers perceive irradiated foods and the factors affecting their acceptance.


title: School and pre-school children with type 1 diabetes during covid-19 quarantine: the synergic effect of parental care and technology

text: Abstract Introduction Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influencesthe outcomesofchildren with T1D, while there are often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents. Aim of the study To evaluate the effectiveness of exclusive return to parental care in pre-school and school children with T1D treated with Tandem Basal IQ system during the COVID-19 pandemic. Patients and methods 22 children (M:F = 14:8) with T1D have been evaluated. We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. Results During the IN-COV period a significantly (p < 0.001) higher median value of TIR (66,41%) was observed as compared to PRE-COV period (61,45%). Patients also showed a statistically significant difference (p < 0.002) between the IN-COV period and the PRE-COV period as concerning the TAR metric: respectively 29,86 ± 10,6 % vs 34,73 ± 12,8 %. The difference between the bolus insulin doses was statistically significant (PRE-COV 5,3 IU/day, IN-COV 7,9 IU/day – p<0.05). Conclusion Our observational real-life study confirms the positive effect of parental care in T1D very young children and demonstrates that during the COVID-19 pandemic it was possible to obtain a good glycometabolic compensation despite the significant change in lifestyle.


title: Determining the impact of commercial feed additives as potential porcine epidemic diarrhea virus mitigation strategies as determined by polymerase chain reaction analysis and bioassay()

text: Mitigation of porcine epidemic diarrhea virus (PEDV) was assessed using two feed additives (0.5% inclusion of a benzoic acid [BA] product and 0.02% inclusion of an essential oil [EO] product; DSM Nutritional Products Inc., Parsippany, NJ), and combination of both products (0.5% BA and 0.02% EO) in spray-dried porcine plasma (SDPP) and a swine gestation diet (FEED) as determined by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and bioassay. Viral RNA quantification was performed at 7 sampling days post-laboratory inoculation (d 0, 1, 3, 7, 14, 21, and 42) and infectivity was assessed via bioassay with 10-d-old pigs. There was a tendency for treatment × feed matrix × day interaction (P = 0.094), in which the cycle threshold (Ct) value increased over time in FEED when treated with both feed additives, whereas there was no increase over time observed in SDPP treated with both feed additives. There was a feed matrix × day interaction (P < 0.001) in which Ct increased over time in FEED, whereas very little increase over time was observed in SDPP. A tendency for a treatment × feed matrix effect (P = 0.085) was observed where FEED treated with the combination of EO and BA had a greater (P < 0.05) PEDV Ct value than other FEED treatments, and all SDPP treatments had the lower PEDV Ct values compared to FEED treatments (P < 0.05). Overall, the combination of both feed additives was most effective at reducing the quantity of genetic material as detected by qRT-PCR (P < 0.001) compared to either additive alone or no feed additive. Virus shedding was observed in the d 7 postinoculation SDPP treatment that was treated with both feed additives, as well as d 0 untreated FEED and d 0 FEED treated with both feed additives. No other treatment bioassay room had detectible RNA shed and detected in fecal swabs or cecal contents. In summary, the combination of EO and BA enhanced the degradation of PEDV RNA in feed but had little impact on RNA degradation in SDPP. Both untreated feed and feed treated with the combination of EO and BA resulted in infection at d 0 post-laboratory inoculation; however, neither set of samples was infective at d 1 postinoculation. In addition, SDPP harbored greater levels of quantifiable RNA for a longer duration of time compared to FEED, and these viral particles remained viable for a longer duration of time indicating differences in viral stability exist between different feed matrices.


title: Integrity of mating behaviors and seasonal reproduction in coyotes (Canis latrans) following treatment with estradiol benzoate

text: Abstract Coyotes (Canis latrans) are seasonally monestrous and form perennial pair-bonds. Breeding is dominated by each pack's alpha male and female, and both sexes share responsibility for territory defense and pup-rearing. They are also opportunistic predators on domestic livestock and pets. But while dominant adults have been implicated as primary killers, depredation is reduced when coyotes are without pups. Contraception, therefore, may represent a non-lethal solution for conflicts between coyotes and humans. Steroid hormones successfully control fertility in some species, but have been considered contraindicated in wildlife and canids in particular; specific concerns include possible induction of aberrant behavior, or uterine and hematopoietic pathologies. Herein we describe a study examining the physiological effectiveness, health safety, and behavioral consequences following treatment of estrous coyotes with exogenous estrogen. We treated captive adult female coyotes in estrus with 0.01mg/kg estradiol benzoate (EB), either before (n =5) or immediately after ovulation (n =6), then documented reproductive outcome, physiological variables and behavioral responses, during and after treatment. Pregnancy was averted in six females treated after ovulation, suggesting that appropriate timing of treatment proved crucial. A transient suppression of sexual behavior was observed, and in some cases, estrus appeared slightly lengthened. However, neither ovulation nor mating behavior was fully suppressed. Importantly, non-pregnant females (and their mates) displayed diestrous socio-sexual behavior similar to pregnant coyotes (behavioral pseudopregnancy). Furthermore, non-pregnant coyotes did not mate again until the next native breeding season, and we observed no deleterious physiological effects during diestrus or subsequent ovarian cycles.


title: Burden and viral aetiology of influenza-like illness and acute respiratory infection in intensive care units

text: Abstract The purpose of this investigation was to study the viral aetiology of influenza-like illness (ILI) and acute respiratory tract infection (ARTI) among patients requiring intensive care unit admission. A cross-sectional retrospective study was carried out in Sicily over a 4-year period. A total of 233 respiratory samples of patients with ILI/ARTI admitted to intensive care units were molecularly analyzed for the detection of a comprehensive panel of aetiologic agents of viral respiratory infections. About 45% of patients was positive for at least one pathogen. Single aetiology occurred in 75.2% of infected patients, while polymicrobial infection was found in 24.8% of positive subjects. Influenza was the most common aetiologic agent (55.7%), especially among adults. Most of patients with multiple aetiology (76.9%) were adults and elderly. Mortality rates among patients with negative or positive aetiology did not significantly differ (52.4% and 47.6%, respectively). Highly transmissible respiratory pathogens are frequently detected among patients with ILI/ARTI admitted in intensive care units, showing the occurrence of concurrent infections by different viruses. The knowledge of the circulation of several types of microorganisms is of crucial importance in terms of appropriateness of therapies, but also for the implication in prevention strategies and hospital epidemiology.


title: Understanding the accessory viral proteins unique to the severe acute respiratory syndrome (SARS) coronavirus

text: Abstract A novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), infected humans in Guangdong, China, in November 2002 and the subsequent efficient human-to-human transmissions of this virus caused profound disturbances in over 30 countries worldwide in 2003. Eventually, this epidemic was controlled by isolation and there has been no human infection reported since January 2004. However, research on different aspects of the SARS-CoV is not waning, as it is not known if this virus will re-emerge, especially since its origins and potential reservoir(s) are unresolved. The SARS-CoV genome is nearly 30kb in length and contains 14 potential open reading frames (ORFs). Some of these ORFs encode for genes that are homologous to proteins found in all known coronaviruses, namely the replicase genes (ORFs 1a and 1b) and the four structural proteins: nucleocapsid, spike, membrane and envelope, and these proteins are expected to be essential for the replication of the virus. The remaining eight ORFs encodes for accessory proteins, varying in length from 39 to 274 amino acids, which are unique to SARS-CoV. This review will summarize the expeditious research on these accessory viral proteins in three major areas: (i) the detection of antibodies against accessory proteins in the serum of infected patients, (ii) the expression, processing and cellular localization of the accessory proteins, and (iii) the effects of the accessory proteins on cellular functions. These in-depth molecular and biochemical characterizations of the SARS-CoV accessory proteins, which have no homologues in other coronaviruses, may offer clues as to why the SARS-CoV causes such a severe and rapid attack in humans, while other coronaviruses that infect humans seem to be more forgiving.


Invited response to the comment on “Dermatology Residents and the Care of COVID-19 Patients”


title: Therapy with a Severe Acute Respiratory Syndrome–Associated Coronavirus–Neutralizing Human Monoclonal Antibody Reduces Disease Severity and Viral Burden in Golden Syrian Hamsters

text: BackgroundImmunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and for the treatment of cancers and autoimmune diseases. MAb 201 is a severe acute respiratory syndrome–associated coronavirus (SARS-CoV)–specific MAb that prevents establishment of viral replication in vitro and prevents viral replication in vivo when administered prophylactically. The efficacy of MAb 201 in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model that supports SARS-CoV replication to high levels and displays severe pathological changes associated with infection, including pneumonitis and pulmonary consolidation MethodsGolden Syrian hamsters that were intranasally inoculated with SARS-CoV were treated with various doses of MAb 201 or an irrelevant MAb 24 h after inoculation. Two to 7 days after infection, the hamsters were killed, and their lungs were collected for evaluation of viral titers and pathological findings ResultsPostexposure treatment with MAb 201 can alleviate the viral burden and associated pathological findings in a golden Syrian hamster model of SARS-CoV infection. After a hamster is treated with MAb 201, its viral burden is reduced by 10(2.4)–10(3.9) 50% tissue-culture infectious doses per gram of tissue, and the severity of associated pathological findings, including interstitial pneumonitis and consolidation, is also remarkably reduced ConclusionsThe demonstration of successful postexposure MAb 201 therapy in an animal model that demonstrates viral replication and associated pulmonary pathological findings suggests that MAb 201 may be useful in the arsenal of tools to combat SARS


title: Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice

text: Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.


Highlights for management of patients with Autoimmune Liver Disease during COVID-19 pandemia


Acute care surgery and post‐operative COVID‐19 pneumonia: a surgical and environmental challenge


title: Anti-Diarrheal Effects of Diosmectite in the Treatment of Acute Diarrhea in Children: A Review

text: Acute diarrhea caused by an infectious organism is highly prevalent, particularly in developing countries, and is usually self-limiting. The condition is a major contributor to the global disease burden and is associated with a significant economic cost. The disease is common in children aged <5 years. It occurs as the result of exposure to a diarrheogenic agent that alters intestinal absorption and/or secretion, resulting in an increase in the volume of water that enters the colon beyond that which can be absorbed. Diarrhea almost always occurs by one or more of four mechanisms: disruption of osmotic forces in the intestine; disruption of normal secretory processes; disruption of epithelial cells or the epithelial tight junctions; or motility disorders. Oral rehydration therapy (ORT) is central to the management of acute diarrhea, and is sufficient to prevent complications due to dehydration in most patients while the disease runs its course. However, ORT has no effect on the duration of the disease or frequency of bowel motions, and any agent that could meet these needs would therefore be a useful addition to ORT. Diosmectite is a natural aluminomagnesium silicate clay with a lamellar, non-fibrous crystalline structure that gives it strong adsorbent properties. Its mechanisms of action are not yet fully understood, but are probably multiple. Diosmectite reduces inflammation, modifies mucus rheologic properties, inhibits mucolysis, and adsorbs bacteria, bacterial enterotoxins, viruses and other potentially diarrheogenic substances. A number of studies have shown that diosmectite reduces the duration of diarrhea and decreases the frequency of bowel motions after 2 days of treatment in children with mild-to-moderate acute diarrhea. Two recent trials have indicated a reduction in stool output with diosmectite. Because of its very favorable safety profile, with no serious adverse effects, diosmectite is frequently used, mainly in European countries but also in Asia and Africa. Diosmectite should be used as an adjunct, not an alternative, to ORT and, when needed, to antibacterial therapy.


Strategies and Recommendations for The Safe Implementation of Vascular Surgery During the Pandemic Period of Novel Coronavirus Pneumonia


About the Cover Vincent van Gogh (1853–1890). The Prison Courtyard (1890)


title: Development of a recombinase polymerase amplification combined with lateral-flow dipstick assay for detection of bovine ephemeral fever virus

text: Abstract Bovine ephemeral fever virus (BEFV), identified as the causative pathogen of bovine ephemeral fever (BEF), is responsible for increasing numbers of epidemics/outbreaks and has a significant harmful effect on the livestock industry. Therefore, a rapid detection assay is imperative for BEFV diagnosis. In this study, we described the development of lateral-flow dipstick isothermal recombinase polymerase amplification (LFD-RPA) assays for detection of BEFV. RPA primers and LF probes were designed by targeting the specific G gene, and the amplification product can be visualized on a simple lateral flow dipstick with the naked eyes. The amplification reaction was performed at 38 °C for 20 min and LFD incubation time within 5 min. The detection limit of this assay was 8 copies per reaction, and there was no cross-reactivity with other bovine infectious viruses such as bovine viral diarrhea virus, infectious bovine rhinotracheitis virus, bovine respiratory syncytial virus, bovine coronavirus, bovine parainfluenza virus type 3, bovine vesicular stomatitis virus. In addition, the assay was performed with total 128 clinical specimens and the diagnostic results were compared with conventional RT-PCR, real-time quantative(q) PCR. The result showed that the coincidence rate of BEFV LFD-RPA and real-time qPCR was 96.09% (123/128), which was higher than conventional RT-PCR. The RPA combined with LFD assay probably provides a rapid and sensitive alternative for diagnosis of BEFV infections outbreak.


title: Lewis acid-promoted cascade reaction for the synthesis of Michael acceptors and its application in a dimerization reaction

text: Abstract An efficient Lewis acid-promoted cascade reaction with dimethyl sulfoxide as a methylene source for the synthesis of Michael acceptors is reported. The key to developing this procedure is the selection of a mild base to modulate the equilibrium of various intermediates in order to drive the reaction forward to the formation of Michael acceptor and dimeric compound products. Extensive studies were performed to gain insight into a possible reaction mechanism.


title: Hantaviruses in the Americas and Their Role as Emerging Pathogens

text: The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae) and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS), with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity.


title: Assessment of availability, ecological feature, and habitat preference of the medicinal herb Houttuynia cordata Thunb in the Brahmaputra Valley of Assam, India

text: Houttuynia cordata Thunb. is a rhizome-bearing aromatic medicinal herb and is restricted to specialized moist habitats. The plant is collected from natural habitats for local consumption and trade. The status of the species and its variations in physiological performance in different habitats were studied in selected sites of geographically different areas of Brahmaputra valley in eastern India. The surveys were conducted in two different growth stages of the plant during 2005–2007. The sites where the species was encountered were marked and a distribution map was prepared. The frequency and density of the plant was higher in the moist habitats with higher organic carbon (0.85 ± 0.05%). Generally, the density, biomass production and growth had significant (P < 0.05) positive relationship with the soil physicochemical properties (linear curve fit). Soil moisture was the most dependent factor for the plant growth and the optimum growth was recorded at 78 ± 5.6% (r(2) = 0.9; P ≤ 0.01). The physiological performance of the plant in all the studied sites were significantly varied (P < 0.05). The growth and development of H. cordata were also different in the flowering and senescence stages. Clay loam soil, average soil pH of 5.9, and 78% soil moisture were the favorable soil characteristics for the better growth of H. cordata and, hence, these data may be considered for conservation of the species.


title: Operational resilience, disruption, and efficiency: Conceptual and empirical analyses

text: Abstract This research develops the notion of operational resilience and investigates its relationship with operational efficiency under differing conditions of operational disruption. Operational resilience is conceptualized as a multi-dimensional construct, consisting of two theoretically distinct components (i.e., disruption absorption and recoverability), which are argued to have unique effects on operational efficiency under varying operational disruption conditions. The study's hypotheses are empirically tested on primary data from a sample of 259 firms in a sub-Saharan African economy. Using structural equation modeling as an analytical tool, the study finds that both disruption absorption and recoverability have positive effects on operational efficiency. Additionally, the study finds that while the effect of disruption absorption on operational efficiency is stronger under conditions of high operational disruption, the effect of recoverability on operational efficiency is stronger under conditions of low operational disruption. A major implication of these findings is that the nature of operational resilience and the disruption circumstances under which it is deployed shape its efficiency value, thus advancing knowledge on the nuances associated with how and when operational resilience influences operational efficiency.


title: Exploring Lifestyle Habits, Physical Activity, Anxiety and Basic Psychological Needs in a Sample of Portuguese Adults during COVID-19

text: This cross-sectional study aimed to characterize the lifestyle habits, anxiety levels and basic psychological needs (BPN), in Portuguese adults during the Coronavirus Disease 2019 (COVID-19) pandemic, including a comparison between genders and age groups. In total, 1404 adults (36.4 ± 11.7 years; 69.6% female) answered sociodemographic data and three instruments: the International Physical Activity Questionnaire, the Basic Need General Satisfaction Scale and the State-Trait Anxiety Inventory. Males revealed higher values for the total energy expenditure (z = −2.26; p = 0.024; [Formula: see text] = 0.004) and for the level of satisfaction of competence (z = −2.62; p = 0.009; [Formula: see text] = 0.005). Females showed higher scores for the anxiety state (z = −7.87; p ≤ 0.001; [Formula: see text] = 0.044) and anxiety trait (z = −6.49; p ≤ 0.001; [Formula: see text] = 0.030). Regarding age, higher values for the anxiety trait (p ≤ 0.001; [Formula: see text] = 0.030) were found in the 18–34 years-old group compared to all the other age groups, also presenting significantly higher values of total energy expenditure (χ² = 13.93; p = 0.008; [Formula: see text] = 0.007) when compared to the 35–44 years-old group. Significant differences were observed between the 18–34 years-old group and the other age groups for the satisfaction of competence (χ² = 40.97; p ≤ 0.001; [Formula: see text] = 0.026), except for the >65 years-old group. Strategies for promoting well-being during periods of social isolation should consider the role of psychological dimensions and lifestyle habits according to the gender or age group.


title: T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-γ responses

text: Abstract Trichothecenes are exquisitely toxic to the gastrointestinal (GI) tract and leukocytes and thus are likely to impair gut immunity. The purpose of this research was to test the hypothesis that the Type A trichothecene T-2 toxin interferes with the gut mucosal immune response to enteric reovirus infection. Mice were exposed i.p. first to 1.75 mg/kg bw T-2 and then 2 h later with 3 × 107 plaque-forming units of reovirus serotype 1, strain Lang (T1/L). As compared to vehicle-treated control, T-2-treated mice had dramatically elevated intestinal plaque-forming viral titers after 5 days and failed to completely clear the virus from intestine by 10 days. Levels of reovirus λ2 core spike (L2 gene) RNA in feces in T-2-treated mice were significantly higher at 1, 3, 5, and 7 days than controls. T-2 potentiated L2 mRNA expression in a dose-dependent manner with as little as 50 μg/kg of the toxin having a potentiative effect. T-2 exposure transiently suppressed induction of reovirus-specific IgA in feces (6 and 8 days) as well as specific IgA and IgG2a in serum (5 days). This suppression corresponded to decreased secretion of reovirus-specific IgA and IgG2a in Peyer's patch (PP) and lamina propria fragment cultures prepared 5 days after infection. T-2 suppressed IFN-γ responses in PP to reovirus at 3 and 7 days as compared to infected controls whereas IL-2 mRNA concentrations were unaffected. PP IL-6 mRNA levels were increased 2-fold 2 h after T-2 treatment, but no differences between infected T-2-exposed and infected vehicle-treated mice were detectable over the next 7 days. Overall, the results suggest that T-2 toxin increased both the extent of GI tract reovirus infection and fecal shedding which corresponded to both suppressed immunoglobulin and IFN-γ responses.


title: Virus‐Like Particles: Models for Assembly Studies and Foreign Epitope Carriers

text: Virus‐like particles (VLPs), formed by the structural elements of viruses, have received considerable attention over the past two decades. The number of reports on newly obtained VLPs has grown proportionally with the systems developed for the expression of these particles. The chapter outlines the recent achievements in two important fields of research brought about by the availability of VLPs produced in a foreign host. These are: (1) The requirements for VLP assembly and (2) the use of VLPs as carriers for foreign epitopes. VLP technology is a rapidly advancing domain of molecular and structural biology. Extensive progress in VLP studies was achieved as the insect cell based protein production system was developed. This baculovirus expression system has many advantages for the synthesis of viral structural proteins resulting in the formation of VLPs. It allows production of large amounts of correctly folded proteins while also providing cell membranes that can serve as structural elements for enveloped viruses. These features give us the opportunity to gain insights into the interactions and requirements accompanying VLP formation that are similar to the assembly events occurring in mammalian cells. Other encouraging elements are the ability to easily scale up the system and the simplicity of purification of the assembled VLPs. The growing number of VLPs carrying foreign protein fragments on their surface and studies on the successful assembly of these chimeric molecules is a promising avenue towards the development of a new technology, in which the newly designed VLPs will be directed to particular mammalian cell types by exposing specific binding domains. The progress made in modeling the surface of VLPs makes them to date the best candidates for the design of delivery systems that can efficiently reach their targets.


title: A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses

text: A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)(3) had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-γ and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.


title: Thyroid Function and Serum Hepatic Enzyme Activity in Dogs after Phenobarbital Administration

text: Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T(4)) concentrations in some dogs. The duration of liver enzyme induction and T(4) concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T(4) (TT(4)), free T(4) (FT(4)), thyroid‐stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma‐glutamyl transferase (GGT) after discontinuation of long‐term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4–6.6 mg/kg PO ql2h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T(4) and FT(4) were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT(4), FT(4), TSH) persisted for 1–4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3–5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6–8 weeks after discontinuation of phenobarbital may indicate hepatic disease.


Heat maps for surveillance and prevention of COVID-19 spread in nursing homes and assisted living facilities


title: Patient-Centeredness during In-Depth Consultation in the Outpatient Clinic of a Tertiary Hospital in Korea: Paradigm Shift from Disease to Patient

text: BACKGROUND: Patient-centered care (PCC) and integrative care approach are widely advocated. However, their implementation usually requires an extended consultation time. Despite significant advances in medical diagnosis and treatment, no studies have examined consultation time and patient centeredness in Korea. METHODS: We conducted a “15-Minute Consultation” for first-time patients in outpatient clinics of 13 departments. A control group was selected from the same physicians' first-time patients, adjusting for age and gender. A total of 275 patients were selected for receiving in-depth consultation and 141 control patients were selected for regular consultation. Data were collected from patients using a questionnaire comprising a patient-centeredness scale and items on potential predictors such as socio-demographic and clinical factors. We also investigated the participating physician's professionalism. RESULTS: As compared to the control group, the in-depth consultation group scored higher on 5 variables associated with PCC, including (patients' perception of) medical professionals, wait and consultation times, treatment, patient advocacy, and patient satisfaction. While 92.4% of patients in the in-depth consultation group reported that the consultation time was sufficient, only 69.0% of those in the control group reported the same (P < 0.01). In the in-depth consultation group, scores on satisfaction level were the highest for the department of internal medicine, followed by departments of surgery and pediatrics. Participating physicians' improved satisfaction following the intervention proved that in-depth consultation facilitated building a rapport with patients. CONCLUSION: This study illustrated that the provision of sufficiently long consultation for serious and rare diseases could improve PCC and physicians' professionalism. Health authorities should reshuffle the healthcare delivery system and provide sufficient consultation time to ensure PCC and medical professionalism.


title: Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013

text: The Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25–1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.


title: Molecular Study and Phylogenetic Analysis of Middle East Respiratory Syndrome Corona Virus (MERSCoV) in Camel and Human

text: Middle East Respiratory Syndrome Corona Virus (MERSCoV) have been reported in Arabian peninsula and sporadic cases in Europe and Asia. This study was conducted to evaluate the genetic analysis of this virus in human and camel at the first time in Iraq. Two hundred samples were collected from camels and human who suffering from respiratory symptoms, these samples treated with RNA extraction kit then amplification the genetic material by PCR which give 5% positive results. The amplicon then sequenced, registration in gene bank of NCBI for getting accession numbers. The local strains give close relationship with neighbor countries as Saudi Arabia and Jordan strains when using MEGA analysis software.


title: An Imported Case of Brucella melitensis Infection in South Korea

text: Brucellosis is a zoonotic infection that is usually transmitted from cattle to humans through ingestion of animal milk, direct contact with animal parts, or inhalation of aerosolized particles. In Korea, brucellosis seem to be transmitted through close contact with blood, fetus, urine, and placenta of domestic cow that has been infected by Brucella abortus, or inhalation of B. arbortus while examining or slaughtering cow. Brucella melitensis infection is rare in Korea and there have been no reported cases of B. melitensis originating from other countries until now. This report details a case of complicated brucellosis with infective spondylitis in a 48-year-old male construction worker recently returned from Iraq. Infection with B. melitensis was confirmed using 16s rRNA sequencing and omp31 gene analysis. The patient was successfully treated using a combination of rifampin, doxycycline, and streptomycin, in accordance with WHO guidelines. This is the first reported case of complicated brucellosis with infective spondylitis in Korea caused by B. melitensis originating from Iraq.


title: Poliovirus RNA Replication Requires Genome Circularization through a Protein–Protein Bridge

text: Abstract The mechanisms and factors involved in the replication of positive stranded RNA viruses are still unclear. Using poliovirus as a model, we show that a long-range interaction between ribonucleoprotein (RNP) complexes formed at the ends of the viral genome is necessary for RNA replication. Initiation of negative strand RNA synthesis requires a 3′ poly(A) tail. Strikingly, it also requires a cloverleaf-like RNA structure located at the other end of the genome. An RNP complex formed around the 5′ cloverleaf RNA structure interacts with the poly(A) binding protein bound to the 3′ poly(A) tail, thus linking the ends of the viral RNA and effectively circularizing it. Formation of this circular RNP complex is required for initiation of negative strand RNA synthesis. RNA circularization may be a general replication mechanism for positive stranded RNA viruses.


title: Aptasensors for viral diagnostics

text: Abstract Novel viral diagnostic tools need to be affordable, fast, accurate and easy to use with sensitivity and specificity equivalent or superior to current standards. At present, viral diagnostics are based on direct detection of viral components or indirect detection by measuring antibodies generated in response to viral infection. While sensitivity of detection and quantification are still important challenges, we expect major advances from new assay formats and synthetic binding molecules, such as aptamers. Compared to traditional antibody-based detection, aptamers could provide faster adaptation to continuously evolving virus strains and higher discriminating capacity between specific virus serotypes. Aptamers are very stable and easily modifiable, so are ideal molecules for detection and chemical sensing applications. Here, we review the use of aptasensors for detection of viral pathogens and consider the feasibility of aptasensors to become standard devices for point-of-care diagnostics of viruses.


title: Synthesis, cytotoxic activity, and SAR analysis of the derivatives of taxchinin A and brevifoliol

text: Abstract Twenty-one derivatives of taxchinin A (1) and brevifoliol (2) were synthesized and evaluated for cytotoxicity against human non-small lung cancer (A549) cell line. Nine derivatives showed potent activity with IC50 values from 0.48 to 6.22μM. 5-Oxo-13-TBDMS-taxchinin A (11) and 5-oxo-13,15-epoxy-13-epi-taxchinin A (15) are the most potent derivatives, with IC50 at 0.48 and 0.75μM, respectively. The structure–activity relationship (SAR) of these compounds established that exocyclic unsaturated ketone at ring C is the key structural element for the activity, while the α,β-unsaturated ketone positioned at ring A has no effect for the activity. The significant cytotoxicity of derivatives 11 and 15 may be due to the conformational change in the taxane rings. The 3D-QSAR study was conducted on this series of compounds, which provided optimal predictive comparative molecular field (CoMFA) model with cross-validated r 2 (q 2) value of 0.64.


title: H1N1 Is Not a Chinese Virus: the Racialization of People and Viruses in Post-SARS China

text: In this article, I trace how the race-making of people, viruses, and the places they share became a powerful means by which Chinese public health professionals made sense of two major infectious outbreaks that threatened to stall or interrupt China’s development: the SARS outbreak of 2003 and the H1N1 influenza pandemic of 2009. By inscribing geographical stability onto infected bodies in motion through the languages of race and genetics, Chinese public health professionals sought to constrain the mobility of infection and, in doing so, to contain the symbolic and material threats to China’s modernity and development that flu-like infections, and the people who carried and spread them, had come to represent. While SARS in this imaginary became a “Chinese” or “Cantonese” disease, H1N1 became a EuroAmerican disease that, when it reached inside China, adhered more easily to those Chinese who did not quite belong. In constructing this imaginary, public health professionals’ racialization of certain groups thought to be infectious joined with the racialization of the infections themselves. H1N1 could not easily infect most Chinese because both the virus and its hosts were racially alien.


title: Expression of miR-155 associated with Toll-like receptors 3, 7, and 9 transcription in the olfactory bulbs of cattle naturally infected with BHV5

text: Bovine herpesvirus 5 (BHV5) infection of young cattle is frequently associated with fatal neurological disease and, as such, represents an attractive model for studying the pathogenesis of viral-induced meningoencephalitis. Following replication in the nasal mucosa, BHV5 invades the central nervous system (CNS) mainly through the olfactory pathway. The innate immune response triggered by the host face to virus replication through the olfactory route is poorly understood. Recently, an upregulation of conserved pathogen-associated molecular pattern, as Toll-like receptors (TLRs), has been demonstrated in the CNS of BHV5 experimentally infected cows. A new perspective to understand host-pathogen interactions has emerged elucidating microRNAs (miRNAs) network that interact with innate immune response during neurotropic viral infections. In this study, we demonstrated a link between the expression of TLRs 3, 7, and 9 and miR-155 transcription in the olfactory bulbs (OB) of 16 cows suffering from acute BHV5-induced neurological disease. The OBs were analyzed for viral antigens and genome, miR-155 and TLR 3, 7, and 9 expression considering three major regions: olfactory receptor neurons (ORNs), glomerular layer (GL), and mitral cell layer (ML). BHV5 antigens and viral genomes, corresponding to glycol-C gene, were detected in all OBs regions by fluorescent antibody assay (FA) and PCR, respectively. TLR 3, 7, and 9 transcripts were upregulated in ORNs and ML, yet only ORN layers revealed a positive correlation between TLR3 and miR-155 transcription. In ML, miR-155 correlated positively with all TLRs studied. Herein, our results evidence miR-155 transcription in BHV5 infected OB tissue associated to TLRs expression specifically ORNs which may be a new window for further studies.


title: Molecular biology of severe acute respiratory syndrome coronavirus

text: The worldwide epidemic of severe acute respiratory syndrome (SARS) in 2003 was caused by a novel coronavirus called SARS-CoV. Coronaviruses and their closest relatives possess extremely large plus-strand RNA genomes and employ unique mechanisms and enzymes in RNA synthesis that separate them from all other RNA viruses. The SARS epidemic prompted a variety of studies on multiple aspects of the coronavirus replication cycle, yielding both rapid identification of the entry mechanisms of SARS-CoV into host cells and valuable structural and functional information on SARS-CoV proteins. These recent advances in coronavirus research have important implications for the development of anti-SARS drugs and vaccines.


Human severe acute respiratory syndrome (SARS) and feline coronaviroses


title: A new SEIR epidemic model with applications to the theory of eradication and control of diseases, and to the calculation of R 0

text: Abstract We present a novel SEIR (susceptible–exposure–infective–recovered) model that is suitable for modeling the eradication of diseases by mass vaccination or control of diseases by case isolation combined with contact tracing, incorporating the vaccine efficacy or the control efficacy into the model. Moreover, relying on this novel SEIR model and some probabilistic arguments, we have found four formulas that are suitable for estimating the basic reproductive numbers R 0 in terms of the ratio of the mean infectious period to the mean latent period of a disease. The ranges of R 0 for most known diseases, that are calculated by our formulas, coincide very well with the values of R 0 estimated by the usual method of fitting the models to observed data.


title: Unusual simultaneous cerebral infarcts in multiple arterial territories in a COVID-19 patient

text: • In the occurrence of new-onset neurological symptoms in COVID-19 patients, we should suspect an acute ischemic stroke and not assume that it is secondary to the respiratory syndrome (hypoxia). Acute ischaemic stroke continues to be a treatable medical emergency also during the SARS-CoV-2 pandemic. • Arterial thrombotic events may not only occur as a complication in severe cases of COVID-19; but can also appear in mild-moderate cases due to other mechanisms. • Several pathogeneses may be behind ischemic strokes in COVID-19, in addition to the more evident coagulopathy associated with the severe infection.


title: Human metapneumovirus as a causative agent of acute bronchiolitis in infants

text: Abstract Background: Human Metapneumovirus (hMPV), has been recently isolated from children with acute respiratory tract infections (RTIs), including bronchiolitis, and classified in the Pneumovirinae subfamily within the Paramyxoviridae family. Objectives: Since most bronchiolitis studies fail to detect any viral pathogen in part of the samples, we sought for the presence of hMPV in a well characterized bronchiolitis cohort. Study design: Nasal washes were obtained from 56 children admitted to the hospital for acute bronchiolitis. RNA extraction and subsequent RT-PCR were used to detect hMPV, and correlated the presence of the virus with clinical characteristics of the disease. Results and conclusions: PCR revealed the presence of hMPV in 16% of bronchiolitis cases, whereas respiratory syncytial virus (RSV; 67.9%) was the most frequently encountered viral pathogen. hMPV was identified either as a unique viral pathogen or co-existed with RSV, with whom they shared a similar seasonal distribution. There were no differences in disease characteristics, either clinical or laboratory, between bronchiolitis cases where hMPV was present and those caused by RSV or other viral pathogens. These findings suggest that hMPV is a common and important causative agent in infants with bronchiolitis, with clinical characteristics similar to that of RSV.


title: SARS-CoV-2 titers in wastewater foreshadow dynamics and clinical presentation of new COVID-19 cases

text: Current estimates of COVID-19 prevalence are largely based on symptomatic, clinically diagnosed cases. The existence of a large number of undiagnosed infections hampers population-wide investigation of viral circulation. Here, we use longitudinal wastewater analysis to track SARS-CoV-2 dynamics in wastewater at a major urban wastewater treatment facility in Massachusetts, between early January and May 2020. SARS-CoV-2 was first detected in wastewater on March 3. Viral titers in wastewater increased exponentially from mid-March to mid-April, after which they began to decline. Viral titers in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 4–10 days earlier in wastewater than in clinical data. We inferred viral shedding dynamics by modeling wastewater viral titers as a convolution of back-dated new clinical cases with the viral shedding function of an individual. The inferred viral shedding function showed an early peak, likely before symptom onset and clinical diagnosis, consistent with emerging clinical and experimental evidence. Finally, we found that wastewater viral titers at the neighborhood level correlate better with demographic variables than with population size. This work suggests that longitudinal wastewater analysis can be used to identify trends in disease transmission in advance of clinical case reporting, and may shed light on infection characteristics that are difficult to capture in clinical investigations, such as early viral shedding dynamics.


title: Characteristics of and Public Health Emergency Responses to COVID-19 and H1N1 Outbreaks: A Case-Comparison Study

text: Background: Recently, the novel coronavirus disease (COVID-19) has already spread rapidly as a global pandemic, just like the H1N1 swine influenza in 2009. Evidences have indicated that the efficiency of emergency response was considered crucial to curb the spread of the emerging infectious disease. However, studies of COVID-19 on this topic are relatively few. Methods: A qualitative comparative study was conducted to compare the timeline of emergency responses to H1N1 (2009) and COVID-19, by using a set of six key time nodes selected from international literature. Besides, we also explored the spread speed and peak time of COVID-19 and H1N1 swine influenza by comparing the confirmed cases in the same time interval. Results: The government’s entire emergency responses to the epidemic, H1N1 swine influenza (2009) completed in 28 days, and COVID-19 (2019) completed in 46 days. Emergency responses speed for H1N1 was 18 days faster. As for the epidemic spread speed, the peak time of H1N1 came about 4 weeks later than that of COVID-19, and the H1N1 curve in America was flatter than COVID-19 in China within the first four months after the disease emerged. Conclusions: The speed of the emergency responses to H1N1 was faster than COVID-19, which might be an important influential factor for slowing down the arrival of the peak time at the beginning of the epidemic. Although COVID-19 in China is coming to an end, the government should improve the public health emergency system, in order to control the spread of the epidemic and lessen the adverse social effects in possible future outbreaks.


title: Escalating infection control response to the rapidly evolving epidemiology of the coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong

text: OBJECTIVE: To describe the infection control preparedness measures undertaken for coronavirus disease (COVID-19) due to SARS-CoV-2 (previously known as 2019 novel coronavirus) in the first 42 days after announcement of a cluster of pneumonia in China, on December 31, 2019 (day 1) in Hong Kong. METHODS: A bundled approach of active and enhanced laboratory surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and contact tracing for healthcare workers (HCWs) with unprotected exposure in the hospitals was implemented. Epidemiological characteristics of confirmed cases, environmental samples, and air samples were collected and analyzed. RESULTS: From day 1 to day 42, 42 of 1,275 patients (3.3%) fulfilling active (n = 29) and enhanced laboratory surveillance (n = 13) were confirmed to have the SARS-CoV-2 infection. The number of locally acquired case significantly increased from 1 of 13 confirmed cases (7.7%, day 22 to day 32) to 27 of 29 confirmed cases (93.1%, day 33 to day 42; P < .001). Among them, 28 patients (66.6%) came from 8 family clusters. Of 413 HCWs caring for these confirmed cases, 11 (2.7%) had unprotected exposure requiring quarantine for 14 days. None of these was infected, and nosocomial transmission of SARS-CoV-2 was not observed. Environmental surveillance was performed in the room of a patient with viral load of 3.3 × 10(6) copies/mL (pooled nasopharyngeal and throat swabs) and 5.9 × 10(6) copies/mL (saliva), respectively. SARS-CoV-2 was identified in 1 of 13 environmental samples (7.7%) but not in 8 air samples collected at a distance of 10 cm from the patient’s chin with or without wearing a surgical mask. CONCLUSION: Appropriate hospital infection control measures was able to prevent nosocomial transmission of SARS-CoV-2.


title: Sensitivity of L132 Cells to Some “New” Respiratory Viruses

text: THERE are several reports of the isolation from cases of human upper respiratory infections of viruses with a structure known previously only in the viruses causing avian infectious bronchitis(1) and mouse hepatitis(2). The first isolate, named B814, was propagated in organ cultures of human embryo respiratory epithelium(3), and most of the other isolates have been made in organ culture(4). Some viruses of humans, of the type 229E, multiply in tissue cultures of human embryo kidney fibroblasts where they cause a slight cytopathic effect, and in human embryo lung fibroblasts where they cause a definite progressive cytopathic effect(5). Those viruses only cultivated in organ culture were detected either by electron, microscopy, or by inoculation into human volunteers, or by stopping the ciliary activity of the organ culture epithelium. It has been proposed that the group of virsues with this morphology should be called “coronaviruses”(6).


title: Rethinking hospital general ward ventilation design using computational fluid dynamics

text: Summary Indoor ventilation with good air quality control minimises the spread of airborne respiratory and other infections in hospitals. This article considers the role of ventilation in preventing and controlling infection in hospital general wards and identifies a simple and cost-effective ventilation design capable of reducing the chances of cross-infection. Computational fluid dynamic (CFD) analysis is used to simulate and compare the removal of microbes using a number of different ventilation systems. Instead of the conventional corridor air return arrangement used in most general wards, air return is rearranged so that ventilation is controlled from inside the ward cubicle. In addition to boosting the air ventilation rate, the CFD results reveal that ventilation performance and the removal of microbes can be significantly improved. These improvements are capable of matching the standards maintained in a properly constructed isolation room, though at much lower cost. It is recommended that the newly identified ventilation parameters be widely adopted in the design of new hospital general wards to minimise cross-infection. The proposed ventilation system can also be retrofitted in existing hospital general wards with far less disruption and cost than a full-scale refurbishment.


docid: hbhunygk

title: Anti-oxidant and Anti-Inflammatory Cyclic Diarylheptanoids from Alnus japonica Stem Bark

text: A new cyclic diarylheptanoid namely alnuheptanoid B (3), along with four known cyclic diarylheptanoids: myricanone (1), (+)-S-myricanol (2), myricanone 5-O- -D-glucopyranoside (4), and (+)-S-myricanol 5-O- -D-glucopyranoside (5) were isolated from the EtOAc fraction of Alnus japonica Steud (family: Betulaceae) stem bark. Their structures were established by different spectroscopic analyses, as well as optical rotation measurement. Compounds 1, 2, 4, and 5 are isolated for the first time from A. japonica. The antioxidant and anti-inflammatory activities of compounds (1-5) were assessed using DPPH assay and carrageenin induced rat paw edema model, respectively. They displayed significant antioxidant activity in relation to propyl gallate (standard antioxidant) at concentration 50 µM. Compound 2 demonstrated anti-inflammatory effect at a dose 10 mg/kg compared with indomethacin (positive control).


title: 10 recommendations for African governments to ensure food security for poor and vulnerable populations during COVID-19

text: In addressing COVID-19, African governments should not forget the livelihoods as well as the food and nutrition security of their citizens. With over 70% of the workforce in the informal sector without any social protection and health insurance, the pandemic could have a devastating impact on income and livelihoods as well as food and nutrition security for workers up and down the food chain. There are ten steps African governments can take to ensure that their response to the disease takes food and nutrition security into account: 1. Protect food supply chains and consider them essential services; 2. Consider fiscal and monetary incentives; 3. Prioritize healthy diets; 4. Use food reserves wisely; 5. Keep food markets open while ensuring safety; 6. Use mobile cash transfers for social protection; 7. Protect farmers and food workers; 8. Prioritize gender equality; 9. Instill a sense of solidarity; and 10. Avoid export bans.


title: COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

text: BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV–host interactome was carried out in order to provide a theoretic host–pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein–protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.


title: An 'elaborated' pseudoknot is required for high frequency frameshifting during translation of HCV 229E polymerase mRNA.

text: The RNA polymerase gene (gene 1) of the human coronavirus 229E is approximately 20 kb in length and is located at the 5' end of the positive-strand genomic RNA. The coding sequence of gene 1 is divided into two large open reading frames, ORF1a and ORF1b, that overlap by 43 nucleotides. In the region of the ORF1a/ORF1b overlap, the genomic RNA displays two elements that are known to mediate (-1) ribosomal frameshifting. These are the slippery sequence, UUUAAAC, and a 3' pseudoknot structure. By introducing site-specific mutations into synthetic mRNAs, we have analysed the predicted structure of the HCV 229E pseudoknot and shown that besides the well-known stem structures, S1 and S2, a third stem structure, S3, is required for a high frequency of frameshifting. The requirement for an S3 stem is independent of the length of loop 2.


title: Acute respiratory infection and influenza‐like illness viral etiologies in Brazilian adults

text: Influenza‐like illness (ILI) definitions have been used worldwide for influenza surveillance. These different case definitions can vary with regard to sensitivity and predictive values for laboratory confirmed influenza. The literature has indicated the inclusion of other viruses may be the cause of these variable results. The objective of the study was to evaluate ILI national sentinel criteria and viral etiologies in adults diagnosed with acute respiratory infection (ARI) and/or ILI from 2001 to 2003 in Sao Paulo, Brazil. Clinical and laboratory evaluations were observed from 420 adults and collected on a daily basis from outpatient care units at University Hospital. The ILI definition included: fever plus at least one respiratory symptom (cough and/or sore throat) and one constitutional symptom (headache, malaise, myalgia, sweat or chills, or fatigue). DFA and RT‐PCR for influenza, parainfluenza, respiratory syncytial virus, adenovirus, enterovirus, coronavirus, rhinovirus, and metapneumovirus were performed on nasal washes and 61.8% resulted positive. The respiratory viruses detected most often were influenza and rhinovirus. ILI was reported for 240/420 patients (57.1%), with influenza and rhinovirus etiologies accounting for 30.9% and 19.6%, respectively. Rhinovirus peak activity was concurrent with the influenza season. These findings highlight the implications of other viruses in ILI etiology and suggest that during the influenza season, this clinical overlap must be considered in the diagnosis and clinical management of patients. J. Med. Virol. 80:1824–1827, 2008. © 2008 Wiley‐Liss, Inc.


title: Evaluation of antirotavirus activity of flavonoids

text: Abstract Flavonoids are dietary components and the most ubiquitous phenolic compounds found in nature, showing a range of pharmacological activities including antiviral action. This study describes the antiviral screening of 60 different flavones and flavonols against human rotavirus (Wa-1 strain) as well as their cytotoxicity in MA104 cells. Cytotoxicity was investigated by cell morphology assessment and antirotavirus activity by cytopathic effect inhibition. Results were expressed as CC50 and IC50, respectively, in order to calculate the selectivity index (SI=CC50/IC50) of each compound. Structure–activity relationships (SAR) were proposed based on antirotavirus activity.


title: The effect of human mobility and control measures on the COVID-19 epidemic in China

text: The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.


title: CovidSens: a vision on reliable social sensing for COVID-19

text: With the spiraling pandemic of the Coronavirus Disease 2019 (COVID-19), it has becoming inherently important to disseminate accurate and timely information about the disease. Due to the ubiquity of Internet connectivity and smart devices, social sensing is emerging as a dynamic AI-driven sensing paradigm to extract real-time observations from online users. In this paper, we propose CovidSens, a vision of social sensing-based risk alert systems to spontaneously obtain and analyze social data to infer the state of the COVID-19 propagation. CovidSens can actively help to keep the general public informed about the COVID-19 spread and identify risk-prone areas by inferring future propagation patterns. The CovidSens concept is motivated by three observations: (1) people have been actively sharing their state of health and experience of the COVID-19 via online social media, (2) official warning channels and news agencies are relatively slower than people reporting their observations and experiences about COVID-19 on social media, and (3) online users are frequently equipped with substantially capable mobile devices that are able to perform non-trivial on-device computation for data processing and analytics. We envision an unprecedented opportunity to leverage the posts generated by the ordinary people to build a real-time sensing and analytic system for gathering and circulating vital information of the COVID-19 propagation. Specifically, the vision of CovidSens attempts to answer the questions: How to distill reliable information about the COVID-19 with the coexistence of prevailing rumors and misinformation in the social media? How to inform the general public about the latest state of the spread timely and effectively, and alert them to remain prepared? How to leverage the computational power on the edge devices (e.g., smartphones, IoT devices, UAVs) to construct fully integrated edge-based social sensing platforms for rapid detection of the COVID-19 spread? In this vision paper, we discuss the roles of CovidSens and identify the potential challenges in developing reliable social sensing-based risk alert systems. We envision that approaches originating from multiple disciplines (e.g., AI, estimation theory, machine learning, constrained optimization) can be effective in addressing the challenges. Finally, we outline a few research directions for future work in CovidSens.


title: Knowledge and attitudes of medical staff in Chinese psychiatric hospitals regarding COVID-19

text: Abstract On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus COVID-19 a pandemic. There are patients in psychiatric hospitals in China who have been infected with COVID-19, however, the knowledge and attitudes of psychiatric hospital staff towards infectious diseases and their willingness to work during the COVID-19 outbreak has not yet been investigated. This study was performed to assess the knowledge and attitudes of medical staff in two Chinese mental health centers during the COVID-19 outbreak. We included 141 psychiatrists and 170 psychiatric nurses in the study. We found that during the COVID-19 epidemic, 89.51% of the medical staff of the psychiatric hospitals studied had extensive knowledge of COVID-19, and 64.63% of them received the relevant training in hospitals. Furthermore, about 77.17% of participants expressed a willingness to care for psychiatric patients suffering from COVID-19 virus infection. Independent predictors of willingness to care for patients included advanced training and experience of caring for patients with COVID-19. In conclusion, this study suggests that increased attention should be paid to the knowledge and attitudes of medical staff at psychiatric hospitals during the COVID-19 outbreak.


title: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2

text: The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne® was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.


title: Proteomic alteration of Marc-145 cells and PAMs after infection by porcine reproductive and respiratory syndrome virus

text: Abstract Viral infections usually result in alterations in the host cell proteome, which determine the fate of infected cells and the progress of pathogenesis. To uncover cellular protein responses in porcine reproductive and respiratory syndrome virus (PRRSV), infected pulmonary alveolar macrophages (PAMs) and Marc-145 cells were subjected to proteomic analysis involving two-dimensional electrophoresis (2-DE) followed by MALDI-TOF-MS/MS identification. Altered expression of 44 protein spots in infected cells was identified in 2D gels, of which the 29 characterised by MALDI-TOF-MS/MS included 17 up-regulated and 12 down-regulated proteins. Some of these proteins were further confirmed at the mRNA level using real-time RT-PCR. Moreover, Western blot analysis confirmed the up-regulation of HSP27, vimentin and the down-regulation of galectin-1. Our study is the first attempt to analyze the cellular protein profile of PRRSV-infected Marc-145 cells using proteomics to provide valuable information about the effects of PRRSV-induced alterations on Marc-145 cell function. Further study of the affected proteins may facilitate our understanding of the mechanisms of PRRSV infection and pathogenesis.


title: WSE, a new sequence distance measure based on word frequencies

text: Abstract In this article, we present a new distance metric, the Weighted Sequence Entropy (WSE), based on the short word composition of biological sequences. As a revision of the classical relative entropy (RE), our metric (1) works equivalently with RE in the case of small k, (2) avoids the degeneracy when some word types are absent in one sequence but not in the other. Experiments on 25 viruses including SARS-CoVs show that our method and RE give exactly the same phylogenetic tree when word length k ⩽ 3 . When k > 3 , our method still works and gets convergent phylogenetic topology but the RE gives degenerate results.


Incidence and patterns of COVID-19 among inflammatory bowel disease patients from the Nancy and Milan cohorts


title: Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets

text: Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.


title: A novel DNA vaccine containing multiple TB-specific epitopes casted in a natural structure (ECANS) confers protective immunity against pulmonary mycobacterial challenge

text: Abstract Epitope-based DNA vaccines designed to induce T cell responses specific for Mycobacterium tuberculosis (M. tb) are being developed as a means of addressing vaccine potency. In this study, we predicted 4 T cell epitopes from ESAT-6, Ag85A/B and CFP-10 antigens and constructed an ECANS (epitopes casted in a natural structure) DNA vaccine by inserting the epitope DNA segments separately into the gene backbone of M. tb-derived HSP65 (heat shock protein 65) carrier. The immunogenicity and protective efficacy of pECANS DNA vaccine were assessed in BALB/c mice after intramuscular immunization with 4 doses of 50μg ECANS DNA and followed by mycobaterial challenge 4 weeks after the last immunization. Compared to plasmid encoding HSP65, pECANS DNA immunization elicited remarkably higher levels of IFN-γ production by both CD4+ and CD8+ T cells, which were coupled with higher frequencies of antigen-specific T cells and higher CTL activity. Significantly enhanced levels of Th1 cytokines (IFN-γ and IL-12) and increased serum IgG2a/IgG1 ratio were also noted, indicating a predominant Th1 immune response achieved by pECANS DNA immunization. In the consequence, a better protection against Mycobacterium bovis BCG challenge was achieved which was evidenced by reduced bacterial loads in lungs and spleens and profound attenuation of lung inflammation and injury. Our results suggested that multi-T cell-epitope based ECANS gene vaccine induced T cell response to multiple T cell epitopes and led to enhanced protection against mycobacterial challenge. This strategy might be a useful platform to design multi-T cell epitope-based vaccine against M. tb infection.


title: 11 Governance of Biodiversity and Health

text: Abstract: The 1968 UNESCO Biosphere Conference (in partnership with the FAO, WHO and the UN) was the first intergovernmental conference to consider both human and health ecology from a scientific point of view. Thus, it has a leading role in addressing health issues related to ecological diversity on a global scale. It insists on the need for integrated, planned, multidisciplinary policy action for the use and conservation of natural resources within the framework of international cooperation.


title: Zielgerichtete Therapie beim metastasierten Mammakarzinom – welche molekularen Tests sind notwendig?

text: In recent years, targeted therapy for breast cancer has received increasingly more attention. In addition to hormone receptors and human epidermal growth factor 2 (HER2), the immunohistochemical detection of programmed cell death ligand 1 (PD-L1) in advanced triple-negative breast cancer and the detection of mutations in the breast cancer 1 (BRCA1) or BRCA2 gene in the patient’s germline and mutations in the phosphatidylinositol 3 kinase (PI3K) pathway are currently relevant when making decisions regarding targeted therapy.


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title: Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals

text: Abstract Viral infection induces translocation of the nucleolar protein GLTSCR2 from the nucleus to the cytoplasm, resulting in attenuation of the type I interferon IFN-β. Addressing the role of GLTSCR2 in viral replication, we detect that knocking down GLTSCR2 by shRNAs results in significant suppression of viral replication in mammalian and chicken cells. Injection of chicken embryo with the GLTSCR2-specific shRNA-1370 simultaneously or 24 h prior to infection with Newcastle disease virus (NDV) substantially reduces viral replication in chicken embryo fibroblasts. Injection of shRNA-1370 into chicken embryo also reduces the replication of avian influenza virus (AIV). In contrast, GLTSCR2-derived protein G4-T, forming α-helical dimers, increases replication of seven various DNA and RNA viruses in cells. Our studies reveal that alteration of the function of cellular GLTSCR2 plays a role in supporting viral replication. GLTSCR2 should be seriously considered as a therapeutic target for developing broad spectrum antiviral agents to effectively control viral infection.