title: Functional Fcgamma Receptor Polymorphisms Are Associated with Human Allergy

text: OBJECTIVE: IgG Fc receptors (FcγRs) play important roles in immune responses. It is not clear whether FcγR receptors play a role in human asthma and allergy. The aim of current study was to investigate whether functional single nucleotide polymorphisms (SNPs) of FcγR genes (FCGR) are associated with human asthma and allergy. METHODS: Functional SNPs of FCGR2A (FcγRIIA-131His>Arg, rs1801274), FCGR2B (FcγRIIB-187Ile>Thr, rs1050501), FCGR2C (FcγRIIC-13Gln>Stop, rs10917661), FCGR3A (FcγRIIIA-158Val>Phe, rs396991), and FCGR3B variants (FcγRIIIB NA1 and NA2) were genotyped in an asthma family cohort including 370 atopy positive, 239 atopy negative, and 169 asthma positive subjects. The genotype and phenotype data (asthma, bronchial hyper-responsiveness, and atopy) of subjects were analyzed using family-based association tests (FBAT) and logistic regression adjusted for age and sex. RESULT: The FcγRIIA-131His>Arg SNP is significantly associated with atopy in a family-based association test (P = 0.00287) and in a logistic regression analysis (P = 0.0269, OR 0.732, 95% CI: 0.555–0.965). The FcγRIIA-131His (or rs1801274-A) allele capable of binding human IgG2 has a protective role against atopy. In addition, the rare FcγRIIB-187Thr (or rs1050501-C) allele defective for the receptor-mediated inhibitory signals is a risk factor for atopy (P = 0.0031, OR 1.758, 95% CI: 1.209–2.556) and IgE production (P<0.001). However, variants of activating FcγRIIIA (rs396991), and FcγRIIIB (NA1 and NA2), and FcγRIIC (rs10917661) are not associated with asthma, BHR, and atopy (P>0.05). CONCLUSIONS: FcγRIIA and FcγRIIB functional polymorphisms may have a role in the pathogenesis of allergy.


Cardio-onco-hematology patients’ management in the context of the current COVID-19 pandemic[[[es]]]Tratamiento de pacientes de cardio-onco-hematología durante la pandemia actual de COVID-19


title: Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project)

text: BACKGROUND: The annual burden of disease caused indoor air pollution, including polluted outdoor air used to ventilate indoor spaces, is estimated to correspond to a loss of over 2 million healthy life years in the European Union (EU). Based on measurements of the European Environment Agency (EEA), approximately 90 % of EU citizens live in areas where the World Health Organization (WHO) guidelines for air quality of particulate matter sized < 2.5 mm (PM(2.5)) are not met. Since sources of pollution reside in both indoor and outdoor air, selecting the most appropriate ventilation strategy is not a simple and straightforward task. METHODS: A framework for developing European health-based ventilation guidelines was created in 2010–2013 in the EU-funded HEALTHVENT project. As a part of the project, the potential efficiency of control policies to health effects caused by residential indoor exposures of fine particulate matter (PM(2.5)), outdoor bioaerosols, volatile organic compounds (VOC), carbon oxide (CO) radon and dampness was estimated. The analysis was based on scenario comparison, using an outdoor-indoor mass-balance model and varying the ventilation rates. Health effects were estimated with burden of diseases (BoD) calculations taking into account asthma, cardiovascular (CV) diseases, acute toxication, respiratory infections, lung cancer and chronic obstructive pulmonary disease (COPD). RESULTS: The quantitative comparison of three main policy approaches, (i) optimising ventilation rates only; (ii) filtration of outdoor air; and (iii) indoor source control, showed that all three approaches are able to provide substantial reductions in the health risks, varying from approximately 20 % to 44 %, corresponding to 400 000 and 900 000 saved healthy life years in EU-26. PM(2.5) caused majority of the health effects in all included countries, but the importance of the other pollutants varied by country. CONCLUSIONS: The present modelling shows, that combination of controlling the indoor air sources and selecting appropriate ventilation rate was the most effective to reduce health risks. If indoor sources cannot be removed or their emissions cannot be limited to an accepted level, ventilation needs to be increased to remove remaining pollutants. In these cases filtration of outdoor air may be needed to prevent increase of health risks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-016-0101-8) contains supplementary material, which is available to authorized users.


title: Contribution of porcine aminopeptidase N to porcine deltacoronavirus infection

text: Porcine deltacoronavirus (PDCoV), a member of genus Deltacoronavirus, is an emerging swine enteropathogenic coronavirus (CoV). Although outstanding efforts have led to the identification of Alphacoronavirus and Betacoronavirus receptors, the receptor for Deltacoronavirus is unclear. Here, we compared the amino acid sequences of several representative CoVs. Phylogenetic analysis showed that PDCoV spike (S) protein was close to the cluster containing transmissible gastroenteritis virus (TGEV), which utilizes porcine aminopeptidase N (pAPN) as a functional receptor. Ectopic expression of pAPN in non-susceptible BHK-21 cells rendered them susceptible to PDCoV. These results indicate that pAPN may be a functional receptor for PDCoV infection. However, treatment with APN-specific antibody and inhibitors did not completely block PDCoV infection in IPI-2I porcine intestinal epithelial cells. pAPN knockout in IPI-2I cells completely blocked TGEV infection but only slightly decreased PDCoV infection. Homologous modeling of pAPN with the S1 C-terminal domain (S1-CTD) of PDCoV or TGEV showed that TGEV S1-CTD adopted β-turns (β1–β2 and β3–β4), forming the tip of a β-barrel, to recognize pAPN. However, only the top residues in the β1–β2 turn of PDCoV S1-CTD had the possibility to support an interaction with pAPN, and the β3–β4 turn failed to contact pAPN. We also discuss the evolution and variation of PDCoV S1-CTD based on structure information, providing clues to explain the usage of pAPN by PDCoV. Taken together, the results presented herein reveal that pAPN is likely not a critical functional receptor for PDCoV, although it is involved in PDCoV infection.


title: Development and evaluation of a one-step multiplex real-time TaqMan(®) RT-qPCR assay for the detection and genotyping of equine G3 and G14 rotaviruses in fecal samples

text: BACKGROUND: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step multiplex TaqMan(®) real-time reverse transcription polymerase chain reaction (RT-qPCR) assay targeting the NSP3 and VP7 genes of ERVA G3 and G14 genotypes for the rapid detection and G-typing directly from fecal specimens. METHODS: A one-step multiplex TaqMan(®) RT-qPCR assay targeting the NSP3 and VP7 genes of ERVA G3 and G14 genotypes was designed. The analytical sensitivity was assessed using serial dilutions of in vitro transcribed RNA containing the target sequences while the analytical specificity was determined using RNA and DNA derived from a panel of group A rotaviruses along with other equine viruses and bacteria. The clinical performance of this multiplex assay was evaluated using a panel of 177 fecal samples and compared to a VP7-specific standard RT-PCR assay and Sanger sequencing. Limits of detection (LOD), sensitivity, specificity, and agreement were determined. RESULTS: The multiplex G3 and G14 VP7 assays demonstrated high specificity and efficiency, with perfect linearity. A 100-fold difference in their analytical sensitivity was observed when compared to the singleplex assays; however, this difference did not have an impact on the clinical performance. Clinical performance of the multiplex RT-qPCR assay demonstrated that this assay had a high sensitivity/specificity for every target (100% for NSP3, > 90% for G3 VP7 and > 99% for G14 VP7, respectively) and high overall agreement (> 98%) compared to conventional RT-PCR and sequencing. CONCLUSIONS: This new multiplex RT-qPCR assay constitutes a useful, very reliable tool that could significantly aid in the rapid detection and G-typing of ERVA strains circulating in the field.


title: A microfluidic immunomagnetic bead-based system for the rapid detection of influenza infections: from purified virus particles to clinical specimens

text: Seasonal and novel influenza infections have the potential to cause worldwide pandemics. In order to properly treat infected patients and to limit its spread, a rapid, accurate and automatic influenza diagnostic tool needs to be developed. This study therefore presents a new integrated microfluidic system for the rapid detection of influenza infections. It integrated a suction-type, pneumatic-driven microfluidic control module, a magnetic bead-based fluorescent immunoassay (FIA) and an end-point optical detection module. This new system can successfully distinguish between influenza A and B using a single chip test within 15 min automatically, which is faster than existing devices. By utilizing the micromixers to thoroughly wash out the sputum-like mucus, this microfluidic system could be used for the diagnosis of clinical specimens and reduced the required sample volume to 40 μL. Furthermore, the results of diagnostic assays from 86 patient specimens have demonstrated that this system has 84.8 % sensitivity and 75.0 % specificity. This developed system may provide a powerful platform for the fast screening of influenza infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10544-013-9753-0) contains supplementary material, which is available to authorized users.


title: Comparison of loop-mediated isothermal amplification assay and smear microscopy with culture for the diagnostic accuracy of tuberculosis

text: BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required. Hence, we assessed the diagnostic performance of Loop-mediated isothermal amplification (LAMP) assay in detecting M.tuberculosis infection in sputum sample compared to LED fluorescent smear microscopy and culture. METHOD: A cross-sectional study was conducted at the University of Gondar Hospital from June 01, 2015 to August 30, 2015. Pulmonary TB diagnosis using sputum LED fluorescence smear microscopy, TB-LAMP assay and culture were done. A descriptive analysis was used to determine demographic characteristics of the study participants. Analysis of sensitivity and specificity for smear microscopy and TB-LAMP compared with culture as a reference test was performed. Cohen’s kappa was calculated as a measure of agreement between the tests. RESULTS: A total of 78 pulmonary presumptive TB patients sputum sample were analyzed. The overall sensitivity and specificity of LAMP were 75 and 98%, respectively. Among smear negative sputum samples, 33.3% sensitivity and 100% specificity of LAMP were observed. Smear microscopy showed 78.6% sensitivity and 98% specificity. LAMP and smear in series had sensitivity of 67.8% and specificity of 100%. LAMP and smear in parallel had sensitivity of 85.7% and specificity of 96%. The agreement between LAMP and fluorescent smear microscopy tests was very good (κ = 0.83, P-value ≤0.0001). CONCLUSIONS: TB-LAMP showed similar specificity but a slightly lower sensitivity with LED fluorescence microscopy. The specificity of LAMP and smear microscopy in series was high. The sensitivity of LAMP was insufficient for smear negative sputum samples.


title: 12.11 Alterations in Blood Components

text: Abstract Cellular blood components include leukocytes, erythrocytes, and platelets. Leukocyte subtypes are neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Red blood cell components include mature erythrocytes and reticulocytes. Increases or decreases in cell counts/concentrations for each of these blood components may occur in response to many stimuli or pathologic conditions, including stress, inflammation, infectious agents, neoplasia, and the toxic effects of endogenous, environmental, or pharmaceutical compounds. Changes may be limited to a few blood components or may be observed in all blood components depending on the stimulus. Morphologic alterations in blood components may also be observed in conjunction with alterations in blood cell counts. Specific examples of conditions that cause alterations in blood components are described, as well as the mechanisms by which many of these specific alterations occur. Many xenobiotics are able to cause similar alterations in blood components through the same or comparable mechanisms, and examples of xenobiotic-induced alterations in blood components are provided.


title: Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats

text: BACKGROUND AND OBJECTIVES: A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951. METHODS: Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval. RESULTS: Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet. CONCLUSION: FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.


title: An optimal control theory approach to non-pharmaceutical interventions

text: BACKGROUND: Non-pharmaceutical interventions (NPI) are the first line of defense against pandemic influenza. These interventions dampen virus spread by reducing contact between infected and susceptible persons. Because they curtail essential societal activities, they must be applied judiciously. Optimal control theory is an approach for modeling and balancing competing objectives such as epidemic spread and NPI cost. METHODS: We apply optimal control on an epidemiologic compartmental model to develop triggers for NPI implementation. The objective is to minimize expected person-days lost from influenza related deaths and NPI implementations for the model. We perform a multivariate sensitivity analysis based on Latin Hypercube Sampling to study the effects of input parameters on the optimal control policy. Additional studies investigated the effects of departures from the modeling assumptions, including exponential terminal time and linear NPI implementation cost. RESULTS: An optimal policy is derived for the control model using a linear NPI implementation cost. Linear cost leads to a "bang-bang" policy in which NPIs are applied at maximum strength when certain state criteria are met. Multivariate sensitivity analyses are presented which indicate that NPI cost, death rate, and recovery rate are influential in determining the policy structure. Further death rate, basic reproductive number and recovery rate are the most influential in determining the expected cumulative death. When applying the NPI policy, the cumulative deaths under exponential and gamma terminal times are close, which implies that the outcome of applying the "bang-bang" policy is insensitive to the exponential assumption. Quadratic cost leads to a multi-level policy in which NPIs are applied at varying strength levels, again based on certain state criteria. Results indicate that linear cost leads to more costly implementation resulting in fewer deaths. CONCLUSIONS: The application of optimal control theory can provide valuable insight to developing effective control strategies for pandemic. Our findings highlight the importance of establishing a sensitive and timely surveillance system for pandemic preparedness.


title: Anxiety and depression levels among pregnant women with COVID‐19

text: We read with great interest the Special Editorial by Dr Thapa and co-authors on the importance of not neglecting emotions of pregnant women during the COVID-19 pandemic1 as maternal mental health can be associated with short and long term risks for their and their children's physical and psychological health. Most studies on COVID-19 in pregnancy have focused on physical effects of the pandemic on infected mothers as well as the possibility of vertical transmission: these tend to eclipse the equally relevant maternal mental health needs during these unprecedented times.


Governments and international institutions should urgently attend to the unjust disparities that COVID-19 is exposing and causing


title: Antiviral reactivities of γδ T cells

text: Abstract The complex antiviral immune mechanisms involve both adaptive and innate reactions mediated by γδ T lymphocytes, whose unique immunosurveillance contributions are analyzed here in different clinical and experimental settings. It is beyond any doubt that the fast, potent, cytotoxic as well as non-cytolytic antiviral activities of γδ T cells are critical in protecting the host against diverse viral pathogens.


title: The perceived effectiveness of MERS-CoV educational programs and knowledge transfer among primary healthcare workers: a cross-sectional survey

text: BACKGROUND: Knowledge transfer of Middle East respiratory syndrome coronavirus (MERS-CoV) involves the dissemination of created/acquired information on MERS-CoV in hospitals, making this information accessible to all healthcare workers (HCWs). This study evaluated the perceived effectiveness of MERS-CoV educational programs and knowledge transfer among primary care HCWs at a hospital in Saudi Arabia that witnessed the largest outbreak of confirmed MERS-CoV cases in this country. METHODS: A survey was distributed among primary care HCWs at five clinics in Saudi Arabia in 2016. Those with non-direct patient care responsibilities were excluded. Their knowledge was evaluated against facts published by Mayo Clinic Foundation, and its percentage mean score (PMS) ± standard deviation was calculated. HCWs’ perceived effectiveness of educational programs and knowledge transfer was classified as negative or positive. RESULTS: Sample comprised of 404 HCWs, of which 64% were females and 36% were males. Almost 26% were ≤ 30 years old, and 42% had > 10 years of work experience. Almost 46.5% were nurses, 23.0% physicians, 18.1% were pharmacists, and 12.4% were technical staff. PMS for knowledge was 71.1 ± 19.4. The prevalence of negative perceptions towards educational programs was 22.5% and of knowledge transfer was 20.8%. Older(> 40 years of age) and more experienced(> 10 years) HCWs had the highest PMS for knowledge(73.4 ± 18.9,P = 0.005 and 76.9 ± 15.7,P < 0.001 respectively). Negative perceptions of educational programs (49.4 ± 20.7; P < 0.001) and knowledge transfer (46.0 ± 19.7; P = 0.001) were associated with a lower knowledge PMS. Males were 2.4[95% confidence interval 1.4–4.2] times and 2.0[1.1–3.5] times more likely to have negative perceptions of educational programs and knowledge transfer (adjusted (adj.)P = 0.001 and adj. P = 0.023, respectively). Physicians/pharmacists were 1.8[1.03–3.11] and 2.8[1.6–5.0] times more likely to have negative perceptions of both outcomes (adj. P = 0.038 and adj. P = 0.001, respectively). Less experienced HCWs were 2.1[1.3–3.5] times and 4.9[2.6–9.2] times more likely to exhibit negative perceptions of the two outcomes (adj. P < 0.001 each). CONCLUSIONS: A negative perception of the effectiveness of MERS-CoV knowledge transfer was associated with poorer knowledge and was more prevalent among male HCWs, physicians/pharmacists and less experienced HCWs. Hospitals should always refer to efficient knowledge sharing and educational strategies that render beneficial outcomes to patients, HCWs, and the public community. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3898-2) contains supplementary material, which is available to authorized users.


title: The paediatric weight management office visit via telemedicine: pre‐ to post‐COVID‐19 pandemic

text: Telemedicine is a powerful tool that erases many logistical barriers to care and may increase access. Due to the need for social distancing, the COVID‐19 pandemic has temporarily reduced in‐person visits for clinical care. Providers, clinical staff and patients are pressed to acutely learn new skills and adapt clinical care through the use of telemedicine whilst administrators, policy makers and regulatory organizations make changes to existing policies to meet this national emergency. Our tertiary care, interdisciplinary paediatric weight management clinic began the use of telemedicine 5 years ago to bring access to an underserved, rural population at their primary care office, which has allowed our clinic to pivot seamlessly to in‐home telemedicine visits during the pandemic. Telemedicine rules and regulations are rapidly changing to meet the COVID‐19 national emergency, but many supports for new telemedicine providers are already in place. In this article, we provide an overview of telemedicine components, policies and regulations. We review the operationalization of our clinic's telemedicine visit prior to the pandemic. We discuss how telemedicine services are impacted by COVID‐19 and key resources are provided. Finally, we reimagine telemedicine services post‐pandemic to expand effective, coordinated health care, particularly for patients with chronic needs such as obesity.


title: COVID-19 and ovarian cancer: Exploring alternatives to intravenous (IV) therapies

text: • The pandemic COVID-19 requires alternative methods and thinking to keep healthcare professionals and patients safe. • In COVID-19 hot spots, oral therapies may be viable alternatives to intravenous therapies for treatment of ovarian cancer. • Minimizing patient visits to hospitals and cancer clinics may help mitigate the spread of SARS-CoV-2.


title: The negative spillover effect of food crises on restaurant firms: Did Jack in the Box really recover from an E. coli scare?

text: Despite the enormous impact of food crises on restaurants, limited understanding of their long-term impacts and associated factors has undermined crisis managers’ ability to handle crisis situations effectively. This article investigated the long-term impact of food crises on the financial performance of restaurant firms and identified the factors that influenced this impact. This explanatory study examined the case of Jack in the Box, whose 1993 Escherichia coli scare was the first and largest restaurant-associated food crisis in modern times. An event study method was used to uncover stock price movements of Jack in the Box, in conjunction with 73 unrelated food crises that occurred from 1994 to 2010. Stock prices of Jack in the Box exhibited significantly negative responses to other firms’ food crises, moreover, the negative spillover effect was stronger if the crisis occurred closer in time, was similar in nature, and was accompanied with no recall execution. These findings shed light on the long-term financial impact of food crises and offer insights for crisis managers to develop more effective crisis management strategies.


title: Recognizing flu-like symptoms from videos

text: BACKGROUND: Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on. RESULTS: In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view. CONCLUSIONS: Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from multiple persons in possibly crowded environments.


title: “Mag ik weer op het spreekuur komen, dokter?”

text: “Dokter, mag ik weer op het spreekuur komen? Ik heb al een aantal dagen pijn in mijn buik, rechts, ook ’s nachts. Ik heb op Thuisarts.nl gekeken en daar staat dat ik u moet bellen.”


title: The immune response to a recombinant Lactococcus lactis oral vaccine against foot-and-mouth disease virus in mice

text: OBJECTIVE: Development of an effective mucosal vaccine to induce specific immune responses against Foot-and-mouth disease virus (FMDV). RESULTS: For this purpose, the FMDV VP1 gene (SPVP1) was optimized and synthesized based on the codon bias of Lactococcus lactis (L. lactis), and then incorporated in the plasmid pNZ8148. L. lactis NZ9000 containing the pNZ8148-SPVP1 recombinant plasmid was used as an oral delivery vehicle to induce anti-FMDV mucosal and systemic immune responses in mice. After confirmation that the SPVP1 protein was expressed successfully in the recombinant L. latic, the mice were orally challenged with NZ9000-pNZ8148, NZ9000-pNZ8148-SPVP1, phosphate-buffered saline as a mock infection group, or with inactivated vaccine as a positive group. Mice immunized with NZ9000-pNZ8148-SPVP1 produced high levels of mucosal secretory IgA (sIgA), antigen-specific serum IgG, IgA, and neutralizing antibodies, and developed stronger cell-mediated immune reactions and significant T spleen lymphocyte proliferation. Furthermore, the recombinant group generated much higher levels of IFN-γ, IL-2, IL-4, IL-5, and IL-10 than the other groups. CONCLUSIONS: Potent immune responses were successfully elicited in mice with FMDV VP1 delivered through L. lactis.


title: Structure-Based Stabilization of Non-native Protein–Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design

text: [Image: see text] Structure-based stabilization of protein–protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases.


title: Public Health Lessons from Severe Acute Respiratory Syndrome a Decade Later

text: The outbreak of severe acute respiratory syndrome in 2002–2003 exacted considerable human and economic costs from countries involved. It also exposed major weaknesses in several of these countries in coping with an outbreak of a newly emerged infectious disease. In the 10 years since the outbreak, in addition to the increase in knowledge of the biology and epidemiology of this disease, a major lesson learned is the value of having a national public health institute that is prepared to control disease outbreaks and designed to coordinate a national response and assist localities in their responses.


title: Display of Porcine Epidemic Diarrhea Virus Spike Protein on Baculovirus to Improve Immunogenicity and Protective Efficacy

text: A new variant of the porcine epidemic diarrhea virus (PEDV) is an emerging swine disease, killing considerable numbers of neonatal piglets in North America and Asia in recent years. To generate immunogens mimicking the complex spike (S) protein folding with proper posttranslational modification to mount a robust immune response against the highly virulent PEDV, two baculoviruses displaying the full-length S protein (S-Bac) and the S1 protein (S1-Bac) of the virulent Taiwan genotype 2b (G2b) PEDV Pintung 52 (PEDV-PT) strain were constructed. Intramuscular immunizations of mice and piglets with the S-Bac and S1-Bac demonstrated significantly higher levels of systemic anti-PEDV S-specific IgG, as compared with control group. Our results also showed that piglets in the S-Bac group elicited superior PEDV-specific neutralizing antibodies than those of the S1-Bac and control groups. The highly virulent PEDV-PT strain challenge experiment showed that piglets immunized with S-Bac and S1-Bac showed milder clinical symptoms with significantly less fecal viral shedding as compared with non-immunized control piglets. More importantly, piglets immunized with the S-Bac exhibited no to mild clinical signs, with a delayed, minimal viral shedding. Our results demonstrated that the S-Bac could serve as a safe, easy to manipulate, and effective vaccine candidate against the PEDV infection.


title: Infections with Influenza A/H3N2/ Subtype in Poland in the 2016/2017 Epidemic Season

text: The 2016/2017 epidemic season was characterized by a lower number of diagnostically tested samples of the nasal and throat swabs and bronchoalveolar lavage fluid, compared with the preceding season. The predominant influenza subtype found was A/H3N2/ which was notably diagnosed in patients over 25 years of age. This subtype was also often diagnosed in older people of 65+ years, which is in line with the risk assessment prepared by the European Center for Disease Prevention and Control (ECDC) at the beginning of the season. The A/H3N2/ subtype was most often diagnosed in the West Pomeranian and Warmian-Masurian Voivodeships. In this epidemic season, there were 11 coinfections of the A/H3N2/ subtype with other influenza and influenza-like viruses recorded in Poland. A different situation had occurred in the 2014/2015 season, when the subtype A/H3N2/ also was predominant, but the virus was most commonly diagnosed in children up to 14 years of age. In both seasons, the least confirmations were observed in patients between 15 and 24 years.


Mers coronavirus infection of rabbits


title: Setting Priorities Fairly in Response to Covid-19: Identifying Overlapping Consensus and Reasonable Disagreement

text: Proposals for allocating scarce lifesaving resources in the face of the covid-19 pandemic have aligned in some ways and conflicted in others. This paper attempts a kind of priority setting in addressing these conflicts. In the first part, we identify points on which we do not believe that reasonable people should differ—even if they do. These are (a) the inadequacy of traditional clinical ethics to address priority-setting in a pandemic; (b) the relevance of saving lives; (c) the flaws of first-come, first-served allocation; (d) the relevance of post-episode survival; (e) the difference between age and other life-expectancy expectancy; and (f) the need to avoid quality-of-life judgments. In the second part, we lay out some positions on which reasonable people can and do differ. These include (a) conflicts between maximizing benefits and priority to the worst off; (b) role-based priority; and (c) whether patients’ existing lifesaving resources should be subject to redistribution.


title: Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus

text: Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human–reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring–summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir–human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses.


Co-infection with Bartonella henselae and Sarcocystis sp. in a 6-year-old male neutered domestic longhair cat with progressive multifocal neurological signs


title: A future for transgenic livestock

text: The techniques that are used to generate transgenic livestock are inefficient and expensive. This, coupled with the fact that most agriculturally relevant traits are complex and controlled by more than one gene, has restricted the use of transgenic technology. New methods for modifying the genome will underpin a resurgence of research using transgenic livestock. This will not only increase our understanding of basic biology in commercial species, but might also lead to the generation of animals that are more resistant to infectious disease.


title: Human bocavirus infections in hospitalized Greek children

text: INTRODUCTION: The epidemiology of human bocavirus (HBoV) infections has not been described in Greece, a south-eastern European country. To define the epidemiological profile and the clinical characteristics associated with HBoV infection in a population of children hospitalized with respiratory tract infection. MATERIAL AND METHODS: During a one-year period throat swab samples were collected from 370 previously healthy children, aged 14 days to 13 years, admitted to two different paediatric wards because of respiratory tract infection. Samples were tested for HBoV by PCR amplifying a part of the NS1 gene. RESULTS: Human bocavirus was detected in 12 children (3.2%). Four of the 12 cases were co-infections, 3 of them with influenza A and 1 with coronavirus OC43. Cases were observed only during the cold months. The mean age of children was 1.8 years (range 2 months to 4 years). The most common symptoms were fever, cough and various degrees of respiratory distress. All children were clinically diagnosed as having lower respiratory tract infections, mainly pneumonia and acute laryngotracheobronchitis, and recovered uneventfully. CONCLUSIONS: HBoV infections occur in Greece mostly among very young children. They accounted for 3.2% of children hospitalized with acute respiratory disease. Cases were observed only in late autumn to early spring.


title: Synthesis and Application of Silver Nanoparticles (Ag NPs) for the Prevention of Infection in Healthcare Workers

text: Silver is easily available and is known to have microbicidal effect; moreover, it does not impose any adverse effects on the human body. The microbicidal effect is mainly due to silver ions, which have a wide antibacterial spectrum. Furthermore, the development of multidrug-resistant bacteria, as in the case of antibiotics, is less likely. Silver ions bind to halide ions, such as chloride, and precipitate; therefore, when used directly, their microbicidal activity is shortened. To overcome this issue, silver nanoparticles (Ag NPs) have been recently synthesized and frequently used as microbicidal agents that release silver ions from particle surface. Depending on the specific surface area of the nanoparticles, silver ions are released with high efficiency. In addition to their bactericidal activity, small Ag NPs (<10 nm in diameter) affect viruses although the microbicidal effect of silver mass is weak. Because of their characteristics, Ag NPs are useful countermeasures against infectious diseases, which constitute a major issue in the medical field. Thus, medical tools coated with Ag NPs are being developed. This review outlines the synthesis and utilization of Ag NPs in the medical field, focusing on environment-friendly synthesis and the suppression of infections in healthcare workers (HCWs).


title: Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model

text: Abstract The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1,000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.


title: KAPITEL 13 Infektionskrankheiten

text: Zur Orientierung Infektionskrankheiten werden durch Pathogene verursacht, die sich im Wirt vermehren: Ektoparasiten, Helminthen, Protozoen, Pilze, Bakterien, Viren, Prionen. Infektionskrankheiten können alle Organe bzw. Organsysteme befallen. Entstehung und Verlauf werden durch Faktoren beeinflusst, die sich grob einteilen lassen in Erreger- und Wirtsfaktoren. Die Kenntnis und richtige Einschätzung dieser Faktoren sind entscheidend für Diagnostik und Therapie dieser Erkrankungen.


title: Lipid nanoparticle technology for therapeutic gene regulation in the liver

text: Hereditary genetic disorders, cancer, and infectious diseases of the liver affect millions of people around the globe and are a major public health burden. Most contemporary treatments offer limited relief as they generally aim to alleviate disease symptoms. Targeting the root cause of diseases originating in the liver by regulating malfunctioning genes with nucleic acid-based drugs s holds great promise as a therapeutic approach. However, employing nucleic acid therapeutics in vivo is challenging due to their unfavorable characteristics. Lipid nanoparticle (LNP) delivery technology is a revolutionary development that has enabled clinical translation of gene (editing) therapies. LNPs can deliver siRNA, mRNA, DNA, or gene-editing complexes, providing opportunities to treat hepatic diseases by silencing pathogenic genes, expressing therapeutic proteins, or correcting genetic defects. Here we discuss the state-of-the-art LNP technology for hepatic gene therapy including formulation design parameters, production methods, preclinical development and clinical translation.


title: Major advances in managing community-acquired pneumonia

text: This article is a non-systematic review of selected recent publications in community-acquired pneumonia, including a comparison of various guidelines. Risk stratification of patients has recently been advanced by the addition of several useful biomarkers. The issue of single versus dual antibiotic treatment remains controversial and awaits a conclusive randomized controlled trial. However, in the meantime, there is a working consensus that more severe patients should receive dual therapy.


title: Assessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in human

text: At present, more than 200 countries and territories are directly affected by the coronavirus disease-19 (COVID-19) pandemic. Incidence and case fatality rate are significantly higher among elderly individuals (age > 60 years), type 2 diabetes and hypertension patients. Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. Two missense and five regulatory SNPs were identified to have differential allelic frequency. Significant linkage disequilibrium (LD) signature was observed in different populations. Modelled protein‒protein interaction (PPI) predicted strong molecular interaction between these two receptors and SARS-CoV-2 spike protein (S1 domain). However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 5′ UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization. Overexpression of CD26 through epigenetic modification at rs13015258-C allele was found critical and could explain the higher SARS-CoV-2 infected fatality rate among type 2 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12041-020-01217-7) contains supplementary material, which is available to authorized users.


Looking Back, Looking Forward


title: Emerging diseases in Bangladesh: Current microbiological research perspective

text: Abstract Bangladesh has experienced a variety of diseases caused by natural dissemination of an array of pathogenic microorganisms into the environment. While cures for these diseases largely depend on the medication strategies of physicians, determining the reasons for disease persistence as well for the onset of reinfection is also essential. Routine diagnosis of common diseases usually means treatment with a range of appropriate medicines; however, failure of these medications because of the drug resistance of microorganisms accompanied by a lack of alertness about the etiology of diseases often leads to fatal results. The present review reports on emerging diseases in Bangladesh and focuses on associated microbiological research into ongoing diseases including enteric, urinary tract, and malarial complications. The viruses associated with acquired immunodeficiency syndrome and hepatitis are also discussed.


title: Modeling and forecasting trend of COVID-19 epidemic in Iran until May 13, 2020

text: Background: COVID-19 is a new disease and precise data are not available about this illness in Iran and in the world. Thus, this study aimed to determine the epidemic trend and prediction of COVID-19 in Iran. Methods: This was a secondary data analysis and modeling study. The daily reports of definitive COVID-19 patients released by Iran Ministry of Health and Medical Education were used in this study. Epidemic projection models of Gompertz, von Bertalanffy, and least squared error (LSE) with percentage error were used to predict the number of hospitalization cases from April 3, 2020 until May 13, 2020. Results: The prediction of the number of patients on April 3, 2020 by von Bertalanffy, Gompertz, and LSE, with 95% confidence interval (CI), were estimated at 44 200 (39 208-53 809), 47 500 (38 907-52 640), and 48 000 (40 000-57 560), respectively. The number of deceased COVID-19 patients was also estimated to be 3100 (2633-3717) individuals by the von Bertalanffy model, 3700 (2900-4310) by Gompertz's model, and 3850 (3200-4580) by LSE. Making predictions about the flat epidemic curve and number of patients based on Gompertz model, will project 67 000 (61 500-87 000) cases. Based on Gompertz and von models, 7900 (6200- 9300) and 4620 (3930- 5550) deaths will occur from May 13 to June 1, 2020, respectively, and then the curve will flatten. Conclusion: In this study, estimations were made based on severely ill patients who were in need of hospitalization. If enforcement and public behavior interventions continue with current trends, the COVID-19 epidemic will be flat from May 13 until July, 2020 in Iran.


title: Severe community-acquired adenovirus pneumonia in an immunocompetent 44-year-old woman: a case report and review of the literature

text: INTRODUCTION: This case report describes a rare condition: community-acquired adenovirus pneumonia in an immunocompetent adult. The diagnosis was achieved by using a multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and highlights the usefulness of these novel molecular diagnostic techniques in patients hospitalized with acute respiratory illness. We also performed a literature search for previously published cases and present a summary of the clinical, laboratory and radiological features of this condition. CASE PRESENTATION: A 44-year-old immunocompetent Caucasian woman was admitted to our hospital with an acute febrile respiratory illness associated with a rash. Her blood tests were non-specifically abnormal, and tests for bacterial pathogens were negative. Her condition rapidly deteriorated while she was in our hospital and required mechanical ventilation and inotropic support. A multiplex real-time RT-PCR assay performed on respiratory specimens to detect respiratory viruses was negative for influenza but positive for adenovirus DNA. The patient recovered on supportive treatment, and antibiotics were stopped after 5 days. CONCLUSIONS: Community-acquired adenovirus pneumonia in immunocompetent adult civilians presents as a non-specific acute febrile respiratory illness followed by the abrupt onset of respiratory failure, often requiring mechanical ventilation. Its laboratory and radiological features are typical of viral infections but also are non-specific. Novel multiplex real-time RT-PCR testing for respiratory viruses enabled us to rapidly make the diagnosis in this case. The new technology could be used more widely in patients with acute respiratory illness and has potential utility for rationalization of the use of antibiotics and improving infection control measures.


title: An implementation of real-time air quality and influenza-like illness data storage and processing platform

text: Abstract Recently, air pollution has become the primary concern in Taiwan as it significantly affected people's health. Some air pollution monitoring, analysis, and prediction systems were proposed to solve the problem. However, there is very little research to see whether the air quality is associated with the Influenza-Like Illness (ILI) disease or not. In this study, a system is needed, in which the air quality data and the influenza-like illness data can be analyzed together to determine their associations accurately and effectively. In this work, a novel integrated platform was implemented by building a cluster environment based on Hadoop, Spark and a visualization environment with ELK Stack as well as a backup storage system based on Ceph object storage architecture. Also, Sqoop and Alluxio were used to solve the inefficiency problem in processing vast amounts of data. The experimental results showed the visualization of air quality and influenza-like illness data collected from 2016 to 2017 in Taichung, Taiwan. Besides, the association analyses and discussion between air quality and influenza-like illness were also presented.


title: Continuous hydroxychloroquine or colchicine therapy does not prevent infection with SARS-CoV-2: Insights from a large healthcare database analysis

text: Abstract Background Some disease-modifying agents commonly used to treat patients with rheumatic diseases/autoimmune disorders, such as hydroxychloroquine and colchicine, are under investigation as potential therapies for the “coronavirus disease 2019” (COVID-19). However, the role of such agents as prophylactic tools is still not clear. Methods This is a retrospective study based on a large healthcare computerized database including all patients that were screened for the “Severe Acute Respiratory Syndrome Coronavirus type 2” (SARS-CoV-2) in the study period from February 23rd 2020 to March 31st 2020. A comparison was conducted between subjects tested positive for SARS-CoV-2 and those found negative in terms of rate of administration of hydroxychloroquine/colchicine therapy. Results An overall sample of 14,520 subjects were screened for SARS-CoV-2 infection and 1317 resulted positive. No significant difference was found in terms of rates of usage of hydroxychloroquine or colchicine between those who were found positive for SARS-CoV-2 and those who were found negative (0.23% versus 0.25% for hydroxychloroquine, and 0.53% versus 0.48% for colchicine, respectively). Conclusion These findings raise doubts regarding the protective role of these medications in the battle against SARS-CoV-2 infection.


title: Vaccines for emerging pathogens: prospects for licensure

text: Globally, there are a number of emerging pathogens. For most, there are no licensed vaccines available for human use, although there is ongoing research and development. However, given the extensive and increasing list of emerging pathogens and the investment required to bring vaccines into clinical use, the task is huge. Overlaid on this task is the risk of anti‐microbial resistance (AMR) acquisition by micro‐organisms which can endow a relatively harmless organism with pathogenic potential. Furthermore, climate change also introduces a challenge by causing some of the insect vectors and environmental conditions prevalent in tropical regions to begin to spread out from these traditional areas, thus increasing the risk of migration of zoonotic disease. Vaccination provides a defence against these emerging pathogens. However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or equivalent status in the United States, Canada and the European Union, making use of a considerable number of regulatory mechanisms that are available prior to licensing. This review covers the status of vaccine development for some of the emerging pathogens, the hurdles that need to be overcome to achieve EUA or an equivalent regional or national status and how these considerations may impact vaccine development for the future, such that a more comprehensive stockpile of promising vaccines can be achieved.


title: Biodegradable Nanoparticle-Entrapped Vaccine Induces Cross-Protective Immune Response against a Virulent Heterologous Respiratory Viral Infection in Pigs

text: Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV). We entrapped PLGA [poly (lactide-co-glycolides)] nanoparticles with killed PRRSV antigens (Nano-KAg) and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses. In a virulent heterologous PRRSV challenge study, Nano-KAg vaccine significantly reduced the lung pathology and viremia, and the viral load in the lungs. Immunologically, enhanced innate and adaptive immune cell population and associated cytokines with decreased secretion of immunosuppressive mediators were observed at both mucosal sites and blood. In summary, we demonstrated the benefits of intranasal delivery of nanoparticle-based viral vaccine in eliciting cross-protective immune response in pigs, a potential large animal model.


title: “The ancient and the new”: is there an interaction between cytomegalovirus and SARS-CoV-2 infection?

text: The SARS-CoV-2 pandemic represents one of the greatest infectious challenges to humanity in recent history. One of the striking features of infection is the heterogeneous clinical response with worse outcomes observed in older patients and those with underlying health conditions. To date the potential impact of previous infection history has been poorly investigated as a potential determinant of risk. Cytomegalovirus (CMV), a persistent herpesvirus infection whose prevalence increases with age, is a major modulator of immune function and several observations suggest that infection might act to influence clinical outcome following SARS-CoV-2 infection. In particular, CMV is associated with the acceleration of immune senescence and has been linked to a range of cardiovascular and metabolic disorders. This review addresses mechanisms by which cytomegalovirus infection may act to worsen the clinical outcome of SARS-CoV-2 infection, discusses how these potential links could be investigated, and assesses the potential significance of any findings that emerge.


title: 40 Cruise Ship Travel

text: Abstract Cruise ships can be amplifiers of infectious diseases because of the close human proximity of semiclosed ship environments. The most common diagnoses of cruise passengers evaluated in cruise ship infirmaries include upper respiratory infections, injury, seasickness, and gastrointestinal illness. Cruise ship passengers may experience clusters of brief self-limited diarrheal disease, although this rate is much lower risk than on land. Certain groups, such as the elderly, pregnant women, and immunocompromised, might be more seriously affected by infectious diseases and stress of travel. Ensure the traveler has medical insurance (health and repatriation) that covers conditions in international waters.


title: Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital

text: Health care workers (HCW) are a high-risk population to acquire SARS-CoV-2 infection from patients or other fellow HCW. This study aims at estimating the seroprevalence against SARS-CoV-2 in a random sample of HCW from a large hospital in Spain. Of the 578 participants recruited from 28 March to 9 April 2020, 54 (9.3%, 95% CI: 7.1–12.0) were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. The cumulative prevalence of SARS-CoV-2 infection (presence of antibodies or past or current positive rRT-PCR) was 11.2% (65/578, 95% CI: 8.8–14.1). Among those with evidence of past or current infection, 40.0% (26/65) had not been previously diagnosed with COVID-19. Here we report a relatively low seroprevalence of antibodies among HCW at the peak of the COVID-19 epidemic in Spain. A large proportion of HCW with past or present infection had not been previously diagnosed with COVID-19, which calls for active periodic rRT-PCR testing in hospital settings.


title: Interplay between Interferon-Mediated Innate Immunity and Porcine Reproductive and Respiratory Syndrome Virus

text: Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non–structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp’s are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.


title: Pediatric Consultation-Liaison Psychiatry: An Update and Review

text: Abstract Background In recent years, there has been an increasing burden of child and adolescent mental illness recognized in the United States, and the need for pediatric mental health care is growing. Pediatric consultation-liaison psychiatrists are increasingly playing a role in the management of medical and psychiatric disease for pediatric patients. The field is a fast-moving one, with understanding of new neuropsychiatric disease entities; reformulation of prior disease entities; and new, interdisciplinary treatments and models of care. Methods In this study, we aim to review recent advances in the field of pediatric consultation-liaison psychiatry, including new diagnostic entities, updated management of frequently encountered clinical presentations, and developments in systems of care. Conclusion The advances in pediatric consultation-liaison psychiatry are broad and serve to promote more streamlined, evidence-based care for the vulnerable population of psychiatrically ill pediatric medical patients. More work remains to determine the most effective interventions for the wide array of presentations seen by pediatric consultation-liaison psychiatrists.


title: Tele-oncology in the COVID-19 era: The way forward?

text: Abstract COVID-19 has had a devastating impact on the care of cancer patients. Thus, tele-oncology has become a necessity to improve cancer care. Several organizations have issued guidelines for its use during COVID-19. Despite certain shortcomings, tele-oncology has great potential to help cancer patients during COVID-19 and in the future.


title: Retrospective Multicenter Study of Respiratory Syncytial Virus Prophylaxis in Korean Children with Congenital Heart Diseases

text: BACKGROUND AND OBJECTIVES: We conducted a review of current data on respiratory syncytial virus (RSV) prophylaxis with palivizumab, in Korean children with congenital heart diseases (CHD). In 2009, the Korean guideline for RSV prophylaxis had established up to five shots monthly per RSV season, only for children <1 year of age with hemodynamic significance CHD (HS-CHD). SUBJECTS AND METHODS: During the RSV seasons in 2009-2015, we performed a retrospective review of data for 466 infants with CHD, examined at six centers in Korea. RESULTS: Infants received an average of 3.7±1.9 (range, 1-10) injections during the RSV season. Fifty-seven HS-CHD patients (12.2%) were hospitalized with breakthrough RSV bronchiolitis, with a recurrence in three patients, one year after the initial check-up. Among patients with simple CHD, only five (1.1%) patients received one additional dose postoperatively, as per the limitations set by the Korean guideline. Among the 30 deaths (6.4%), five (1.1%) were attributed to RSV infection; three to simple CHD, one to Tetralogy of Fallot, and one to hypertrophic cardiomyopathy (HCM). Of the three HCM patients that exceeded guidelines for RSV prophylaxis, two (66.6%) were hospitalized, and one died of RSV infection (33.3%). CONCLUSION: In accordance to the Korean guideline, minimal injections of palivizumab were administered to patients having HS-CHD <one year of age during the RSV season; the risk of RSV infection remains significant among children with simple CHD, cardiomyopathy, and children above the age of one year with HS-CHD.


title: Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial

text: BACKGROUND: Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch–anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis. METHODS: Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation. DISCUSSION: On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.


title: Rapid and Effective Virucidal Activity of Povidone-Iodine Products Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA)

text: INTRODUCTION: Since the first case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was reported in 2012, the virus has infected more than 1300 individuals in 26 countries, and caused more than 480 deaths. Human-to-human transmission requires close contact, and has typically occurred in the healthcare setting. Improved global awareness, together with improved hygiene practices in healthcare facilities, has been highlighted as key strategies in controlling the spread of MERS-CoV. This study tested the in vitro efficacy of three formulations of povidone iodine (PVP-I: 4% PVP-I skin cleanser, 7.5% PVP-I surgical scrub, and 1% PVP-I gargle/mouthwash) against a reference virus (Modified vaccinia virus Ankara, MVA) and MERS-CoV. METHODS: According to EN14476, a standard suspension test was used to assess virucidal activity against MVA and large volume plating was used for MERS-CoV. All products were tested under clean (0.3 g/L bovine serum albumin, BSA) and dirty conditions (3.0 g/L BSA + 3.0 mL/L erythrocytes), with application times of 15, 30, and 60 s for MVA, and 15 s for MERS-CoV. The products were tested undiluted, 1:10 and 1:100 diluted against MVA, and undiluted against MERS-CoV. RESULTS: A reduction in virus titer of ≥4 log(10) (corresponding to an inactivation of ≥99.99%) was regarded as evidence of virucidal activity. This was achieved versus MVA and MERS-CoV, under both clean and dirty conditions, within 15 s of application of each undiluted PVP-I product. CONCLUSION: These data indicate that PVP-I-based hand wash products for potentially contaminated skin, and PVP-I gargle/mouthwash for reduction of viral load in the oral cavity and the oropharynx, may help to support hygiene measures to prevent transmission of MERS-CoV. FUNDING: Mundipharma Research GmbH & Co. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0091-9) contains supplementary material, which is available to authorized users.


title: NS2 Protein of Hepatitis C Virus Interacts with Structural and Non-Structural Proteins towards Virus Assembly

text: Growing experimental evidence indicates that, in addition to the physical virion components, the non-structural proteins of hepatitis C virus (HCV) are intimately involved in orchestrating morphogenesis. Since it is dispensable for HCV RNA replication, the non-structural viral protein NS2 is suggested to play a central role in HCV particle assembly. However, despite genetic evidences, we have almost no understanding about NS2 protein-protein interactions and their role in the production of infectious particles. Here, we used co-immunoprecipitation and/or fluorescence resonance energy transfer with fluorescence lifetime imaging microscopy analyses to study the interactions between NS2 and the viroporin p7 and the HCV glycoprotein E2. In addition, we used alanine scanning insertion mutagenesis as well as other mutations in the context of an infectious virus to investigate the functional role of NS2 in HCV assembly. Finally, the subcellular localization of NS2 and several mutants was analyzed by confocal microscopy. Our data demonstrate molecular interactions between NS2 and p7 and E2. Furthermore, we show that, in the context of an infectious virus, NS2 accumulates over time in endoplasmic reticulum-derived dotted structures and colocalizes with both the envelope glycoproteins and components of the replication complex in close proximity to the HCV core protein and lipid droplets, a location that has been shown to be essential for virus assembly. We show that NS2 transmembrane region is crucial for both E2 interaction and subcellular localization. Moreover, specific mutations in core, envelope proteins, p7 and NS5A reported to abolish viral assembly changed the subcellular localization of NS2 protein. Together, these observations indicate that NS2 protein attracts the envelope proteins at the assembly site and it crosstalks with non-structural proteins for virus assembly.


title: Global Antimicrobial Stewardship with a Focus on Low- and Middle-Income Countries

text: Abstract Antimicrobial resistance is a global public health crisis. Antimicrobial Stewardship involves adopting systematic measures to optimize antimicrobial use, decrease unnecessary antimicrobial exposure and to decrease the emergence and spread of resistance. Low- and middle-income countries (LMICs) face a disproportionate burden of antimicrobial resistance and also face challenges related to resource availability. Although challenges exist, the World Health Organization has created a practical toolkit for developing Antimicrobial Stewardship Programs (ASPs) that will be summarized in this article.


title: EST analysis reveals putative genes involved in glycyrrhizin biosynthesis

text: BACKGROUND: Glycyrrhiza uralensis is one of the most popular medicinal plants in the world and is also widely used in the flavoring of food and tobacco. Due to limited genomic and transcriptomic data, the biosynthetic pathway of glycyrrhizin, the major bioactive compound in G. uralensis, is currently unclear. Identification of candidate genes involved in the glycyrrhizin biosynthetic pathway will significantly contribute to the understanding of the biosynthetic and medicinal chemistry of this compound. RESULTS: We used the 454 GS FLX platform and Titanium regents to produce a substantial expressed sequence tag (EST) dataset from the vegetative organs of G. uralensis. A total of 59,219 ESTs with an average read length of 409 bp were generated. 454 ESTs were combined with the 50,666 G. uralensis ESTs in GenBank. The combined ESTs were assembled into 27,229 unique sequences (11,694 contigs and 15,535 singletons). A total of 20,437 unique gene elements representing approximately 10,000 independent transcripts were annotated using BLAST searches (e-value ≤ 1e-5) against the SwissProt, KEGG, TAIR, Nr and Nt databases. The assembled sequences were annotated with gene names and Gene Ontology (GO) terms. With respect to the genes related to glycyrrhizin metabolism, genes encoding 16 enzymes of the 18 total steps of the glycyrrhizin skeleton synthesis pathway were found. To identify novel genes that encode cytochrome P450 enzymes and glycosyltransferases, which are related to glycyrrhizin metabolism, a total of 125 and 172 unigenes were found to be homologous to cytochrome P450s and glycosyltransferases, respectively. The cytochrome P450 candidate genes were classified into 32 CYP families, while the glycosyltransferase candidate genes were classified into 45 categories by GO analysis. Finally, 3 cytochrome P450 enzymes and 6 glycosyltransferases were selected as the candidates most likely to be involved in glycyrrhizin biosynthesis through an organ-specific expression pattern analysis based on real-time PCR. CONCLUSIONS: Using the 454 GS FLX platform and Titanium reagents, our study provides a high-quality EST database for G. uralensis. Based on the EST analysis, novel candidate genes related to the secondary metabolite pathway of glycyrrhizin, including novel genes encoding cytochrome P450s and glycosyltransferases, were found. With the assistance of organ-specific expression pattern analysis, 3 unigenes encoding cytochrome P450s and 6 unigenes encoding glycosyltransferases were selected as the candidates most likely to be involved in glycyrrhizin biosynthesis.


title: Activation of P2X(7) Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection

text: Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X(7) receptor (P2X(7)R) is required for induction of inflammatory mediators. We also showed that ATP-P2X(7)R signaling regulates inflammasome activation as inhibition or deficiency of P2X(7)R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X(7)R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X(7)R or caspase-1 showed higher rates of survival. The improved survival in the P2X(7)R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the inflammasome pathway and regulates inflammatory responses.


title: Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection

text: The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-β-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon (IFN) regulatory factor 3 and type I IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.


title: Impact of BSE on the biotechnology industry — detection and risk assessment

text: This feature briefly looks at filtration technologies that are being developed by Pall Corp to reduce the potential risk of ‘Mad Cow Disease’ in biological products and drugs. It also provides details of proprietary technology that is designed to reduce prions from blood prior to a transfusion.


title: Society–Space

text: Our conception of society–space determines the vantage point from which we critique and transform the social world; the subjects and processes we deem significant; and their relation to a social whole. This article treats four broad frameworks engaged by geographers, each providing distinct conceptual insights about society and space. In the first, a Marxist view of inequity, society–space is a ‘structured coherence’ – a sociospatial formation, whose territorial boundaries approximate politicojuridical boundaries. Geographers' work on the sociospatial dialectic, spatial fix, and time–space compression have leavened understandings of the spatial dynamics in this approach. The second, a post-structuralist/Foucauldian approach, sees society–space as a ‘strategic field’. Space forms part of the technology of governance that constitutes subjects either as normal/abnormal, legal/illegal, or through states of exception – such as the enemy noncombatant or the illegal alien. In the third, a post-structuralist/feminist approach, society–space is seen as a ‘performative field’ in which subjects negotiate doubled positions and paradoxical spaces – affording insights into larger societal constructs such as the gendering of public/private spheres; racialized people's passing in a white world; or transsexuals performance of sexuality. In the fourth, a Deleuzian approach, society–space is an ‘immanent field’ in which subjects continuously transform themselves, hybridizing, engaging in acts of conjunction, connection, or collaboration with their milieu. Society–space is understood as stabilizing from the composite lattice of practices that are coded and channeled into a kind of social machine.


title: Response of chiropractic organizations to the COVID-19 pandemic: A descriptive report

text: ABSTRACT Objective The purpose of this report is to describe actions by chiropractic entities during the early stages of the coronavirus disease-2019 (COVID-19) pandemic. Methods Large entities that support chiropractic education or practice were invited to participate in this report. Leaders of various entities were emailed an invitation. A designee who was assigned by the leader provided a brief synopsis of actions the entity had taken in response to the COVID-19 pandemic. Only entities that responded are included in this report. Results Five entities agreed to participate: The Council on Chiropractic Education, Association of Chiropractic Colleges, Federation of Chiropractic Licensing Boards, National Board of Chiropractic Examiners, and the NCMIC. Common themes included (1) recognizing the crisis and taking action; (2) establishing a safe working environment for staff so that services could continue; (3) delivering communications to stakeholders (chiropractic students, practitioners, licensing boards, and others) to guide decisions and direct actions; and (4) continuing to monitor the situation and respond as new information becomes available. Conclusion These entities serve a large portion of the chiropractic profession. They have been quick to respond in a responsible, compassionate, and supportive manner to assist chiropractic licensing boards, practitioners, and students during the COVID-19 pandemic. These findings are encouraging as the chiropractic profession looks to the future as it navigates changes in education and the healthcare environment in the months and years ahead.


title: Physiotherapy Care of Patients with Coronavirus Disease 2019 (COVID-19) - A Brazilian Experience

text: Some patients with coronavirus disease (COVID-19) present with severe acute respiratory syndrome, which causes multiple organ dysfunction, besides dysfunction of the respiratory system, that requires invasive procedures. On the basis of the opinions of front-line experts and a review of the relevant literature on several topics, we proposed clinical practice recommendations on the following aspects for physiotherapists facing challenges in treating patients and containing virus spread: 1. personal protective equipment, 2. conventional chest physiotherapy, 3. exercise and early mobilization, 4. oxygen therapy, 5. nebulizer treatment, 6. non-invasive ventilation and high-flow nasal oxygen, 7. endotracheal intubation, 8. protective mechanical ventilation, 9. management of mechanical ventilation in severe and refractory cases of hypoxemia, 10. prone positioning, 11. cuff pressure, 12. tube and nasotracheal suction, 13. humidifier use for ventilated patients, 14. methods of weaning ventilated patients and extubation, and 15. equipment and hand hygiene. These recommendations can serve as clinical practice guidelines for physiotherapists. This article details the development of guidelines on these aspects for physiotherapy of patients with COVID-19.


title: Analysis of epidemic spreading process in multi-communities

text: Abstract In practice, an epidemic might be spreading among multi-communities; while the communities are usually intra-connected. In this manuscript, each community is modeled as a multiplex network (i.e., virtual layer and physical one). The connections inside certain community are referred as inter-contacts while the intra-contacts denote the connections among communities. For the epidemic spreading process, the traditional susceptible-infected-recovered (SIR) model is adopted. Then, corresponding state transition trees are determined and simulations are conducted to study the epidemic spreading process in multi-communities. Here, the effect of incorporating virtual layer on the range of individual affected by the epidemic is pursued. As illustrated, multi-summits are incurred if the spreading in multi-communities is considered; furthermore, the disparity between summits varies. This is affected by various factors. As indicated, the incorporation of virtual layer is capable of reducing the proportion of individuals being affected; moreover, disparity of different summits is likely to be increased regarding with scenarios of excluding virtual layer. Furthermore, the summit is likely to be postponed if virtual layer is incorporated.


title: Coronavirus Reverse Genetics and Development of Vectors for Gene Expression

text: Knowledge of coronavirus replication, transcription, and virus-host interaction has been recently improved by engineering of coronavirus infectious cDNAs. With the transmissible gastroenteritis virus (TGEV) genome the efficient (>40 μg per 10(6) cells) and stable (>20 passages) expression of the foreign genes has been shown. Knowledge of the transcription mechanism in coronaviruses has been significantly increased, making possible the fine regulation of foreign gene expression. A new family of vectors based on single coronavirus genomes, in which essential genes have been deleted, has emerged including replication-competent, propagation-deficient vectors. Vector biosafety is being increased by relocating the RNA packaging signal to the position previously occupied by deleted essential genes, to prevent the rescue of fully competent viruses that might arise from recombination events with wild-type field coronaviruses. The large cloning capacity of coronaviruses (>5 kb) and the possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, has increased the potential of coronaviruses as vectors for vaccine development and, possibly, gene therapy.


title: Respiratory health, allergies, and the farm environment: design, methods and enrollment in the observational Wisconsin Infant Study Cohort (WISC): a research proposal

text: Epidemiologic and cross-sectional studies suggest that early life farming and animal exposures are associated with major health benefits, influencing immune development and modifying the subsequent risk of allergic diseases, including asthma. The Wisconsin Infant Study Cohort (WISC) study was established in central Wisconsin to test the hypothesis that early life animal farm exposures are associated with distinct innate immune cell maturation trajectories, decreased allergen sensitization and reduced respiratory viral illness burden during the first 2 years of life. Beginning in 2013, a total of 240 families have been enrolled, 16,522 biospecimens have been collected, and 4098 questionnaires have been administered and entered into a secure database. Study endpoints include nasal respiratory virus identification and respiratory illness burden score, allergic sensitization, expression of allergic disease, and anti-viral immune response maturation and profiles. The WISC study prospective design, broad biospecimen collections, and unique US rural community will provide insights into the role of environmental exposures on early life immune maturation profiles associated with protection from allergic sensitization and significant respiratory viral disease burden. The WISC study findings will ultimately inform development of new strategies to promote resistance to severe respiratory viral illnesses and design primary prevention approaches for allergic diseases for all infants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-019-4448-0) contains supplementary material, which is available to authorized users.


title: Study of Particle Dispersion on One Bed Hospital using Computational Fluid Dynamics

text: Abstract Increasing concerns about the spread of airborne disease in hospital such as severe acute respiratory syndrome (SARS), chickenpox, measles, tuberculosis and novel swine-origin influenza A (H1N1) have attracted public attention. A present study was carried out to look for the source of contamination (patient itself) and examine the route of contaminant transfer in the hospital. This article provides recommendation for future work to improve the yield and save the energy consumption simultaneously. The risk of airborne infection can be minimized in hospital wards by using a high air change rate. The Local mean age of air will decrease with an increasing flow rate because the source must be considered to be constant. The location of the outlet openings plays an important role for the transfer of the contaminant particle in the hospital.


title: Mechanisms of virus‐induced asthma exacerbations: state‐of‐the‐art. A GA(2)LEN and InterAirways document

text: Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti‐inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research.


title: Next-Generation High-Throughput Functional Annotation of Microbial Genomes

text: Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community.


title: An investigation of mental health status of children and adolescents in China during the outbreak of COVID-19

text: OBJECTIVE: : The sudden outbreak of Coronavirus Disease 2019 (COVID-19) has had a dramatic effect on the mental health of the public. In the present study, we demonstrated the psychological effects on children and adolescents associated with the epidemic . METHODS: : By using convenience sampling method, questionnaires, such as Spence Child Anxiety Scale, Child Depression Inventory and Coping style Scale, were distributed to participating 359 children and 3254 adolescents online. RESULTS: : The anxiety levels of children and adolescents were (23.87±15.79) and (29.27±19.79), respectively. 22.28% respondents were suffering from depressive symptoms. Seven significant factors associated with increased levels of anxiety, including female, resident in urban regions, emotion-focused coping style. Nine factors associated with increased levels of depression, such as smartphone addiction (OR 1.411, 95% CI 1.099–1.180), Internet addiction (OR 1.844, 95% CI 1.209–2.811), and resident in Hubei province (OR 3.107, 95% CI 1.252–7.708). Two additional factors associated with decreased levels of depressive symptoms: hours spend on Internet per day before the epidemic (OR 0.652, 95% CI 0.609–0.697) and tendency to apply problem-focused coping style (OR 0.937, 95% CI 0.923–0.951). CONCLUSION: : Our findings indicate that the COVID-19 outbreak has had a significant psychosocial impact on children and adolescents. Findings of current levels of anxiety and depression not only highlight the need to address emotional distress for children and adolescents during the epidemic but also provide researchers with scientific fundamentals to formulate targeted interventions based on the significant influencing factors.


title: Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate

text: Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.


title: Tim-3 finds its place in the cancer immunotherapy landscape

text: The blockade of immune checkpoint receptors has made great strides in the treatment of major cancers, including melanoma, Hodgkin’s lymphoma, renal, and lung cancer. However, the success rate of immune checkpoint blockade is still low and some cancers, such as microsatellite‐stable colorectal cancer, remain refractory to these treatments. This has prompted investigation into additional checkpoint receptors. T-cell immunoglobulin and mucin domain 3 (Tim-3) is a checkpoint receptor expressed by a wide variety of immune cells as well as leukemic stem cells. Coblockade of Tim-3 and PD-1 can result in reduced tumor progression in preclinical models and can improve antitumor T-cell responses in cancer patients. In this review, we will discuss the basic biology of Tim-3, its role in the tumor microenvironment, and the emerging clinical trial data that point to its future application in the field of immune-oncology.


title: Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil [MMF], lopinavir/ritonavir, and interferon-β1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon-β1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores ↓50.9%–95.0% and ↓weight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung (↓0.59–1.06 log(10) copies/glyceraldehyde 3-phosphate dehydrogenase [GAPDH]; P < .050) and extrapulmonary (↓0.11–1.29 log(10) copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads (↑0.15–0.54 log(10) copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0–33% (lopinavir/ritonavir-treated and interferon-β1b-treated). Lopinavir/ritonavir and interferon-β1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used.


title: PSYCHOTIC SYMPTOMS IN COVID-19 PATIENTS. A RETROSPECTIVE DESCRIPTIVE STUDY.

text: Psychotic symptoms have been related to other coronavirus infections. We conducted a single-centre retrospective and observational study to describe new-onset psychotic episodes in COVID-19 patients. Ten patients infected by the novel coronavirus with psychotic symptoms and no previous history of psychosis were identified by the emergency and liaison psychiatry departments. Nine of the cases presented with psychotic symptoms at least two weeks after the first somatic manifestations attributed to COVID-19 and receiving pharmacological treatment. Structured delusions mixed with confusional features were the most frequent clinical presentations. Hence, COVID-19 patients can develop psychotic symptoms as a consequence of multiple concurrent factors.