title: Impact of multiplex respiratory virus testing on antimicrobial consumption in adults in acute care: a randomized clinical trial

text: Abstract Objectives Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. Methods We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. Results In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI –0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI –0.6 to 2.4, p 0.235). Conclusions Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.


title: Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS-CoV

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC(50) value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.


title: Training Oncologists in the Time of COVID‐19

text: In this commentary, the authors explore the short‐ and long‐term challenges of balancing education and oncologic care from the epicenter of the COVID‐19 pandemic. Once local conditions allow for resumption of outpatient care, the authors discuss how now is an especially important time to prioritize educating trainees.


title: Factors influencing the wearing of facemasks to prevent the severe acute respiratory syndrome among adult Chinese in Hong Kong

text: Abstract Background. The global outbreak of the severe acute respiratory syndrome (SARS) in 2003 has been an international public health threat. Quick diagnostic tests and specific treatments for SARS are not yet available; thus, prevention is of paramount importance to contain its global spread. This study aimed to determine factors associating with individuals' practice of the target SARS preventive behavior (facemask wearing). Methods. A total of 1329 adult Chinese residing in Hong Kong were surveyed. The survey instrument included demographic data, measures on the five components of the Health Belief Model, and the practice of the target SARS preventive behavior. Logistic regression analyses were conducted to determine rates and predictors of facemask wearing. Results. Overall, 61.2% of the respondents reported consistent use of facemasks to prevent SARS. Women, the 50–59 age group, and married respondents were more likely to wear facemasks. Three of the five components of the Health Belief Model, namely, perceived susceptibility, cues to action, and perceived benefits, were significant predictors of facemask-wearing even after considering effects of demographic characteristics. Conclusions. The Health Belief Model is useful in identifying determinants of facemask wearing. Findings have significant implications in enhancing the effectiveness of SARS prevention programs.


title: A case of improved oxygenation in SARS-CoV-2 positive patient on nasal cannula undergoing prone positioning

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. It has placed societal and financial burden on the globe. Its rapid progressions from mild URI symptoms to severe acute respiratory distress syndrome (ARDS) in a matter of days is the underlying reason as to why the world is struggling to keep up with ventilator production. In this case report, we went about proning a corona virus positive patient for 6–8hrs as a potential early intervention to prevent progression to ARDS. Our patient was initially in acute hypoxemic respiratory failure and placed on nasal cannula. He was started on hydroxychloroquine and azithromycin with no improvement of symptoms. However within the span of few hours of proning he experienced significant symptomatic relief with improvement of oxygenation. His oxygen saturation improved drastically and eventually was taken off of nasal cannula and discharged within span of one day of proning.


docid: kgjfuzcv

title: Stress and anxiety among university students in France during Covid-19 mandatory confinement

text: While necessary from a public health standpoint, Covid-19 confinement strategies are often contrary to evidence-based therapies used to treat mental disorders. University students may be particularly vulnerable to mental health problems, but recent studies have indicated only a negligible impact of confinement strategies. French respondents to a World Mental Health survey of university students completed questions concerning Covid-19 confinement. The sample experienced increased anxiety as well as moderate to severe stress during confinement. Respondents who did not relocate to live with parents were disproportionately affected. Knowledge of confinement effects may be used to reduce its negative impact in vulnerable populations.


title: Association between obesity and clinical prognosis in patients infected with SARS-CoV-2

text: BACKGROUND: It is well established that obesity is a disease of sustained low-grade inflammation. However, it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. In this study, we aimed to investigate whether obesity played a role in clinical manifestations and prognosis in patients infected with SARS-CoV-2. METHODS: This is a retrospective multicenter clinical study. A total of 96 patients hospitalized with SARS-CoV-2 infection were enrolled from Dongguan People’s Hospital, Nanfang hospital and the First Affiliated Hospital of Xiamen University between 23 January and 14 February 2020. Demographic and clinical data were extracted from medical records. Acute respiratory distress syndrome (ARDS) was defined as oxygenation index (PaO(2)/FiO(2)) ≤ 300 mmHg. We grouped patients through the body mass index (BMI). Associations were examined using the t test, χ(2) test and multivariate logistic forward regression test. RESULTS: Patients with BMI < 24 were significantly younger (P = 0.025) with lower creatine kinase (P = 0.013), lower diastolic pressure blood (P = 0.035), lower serum creatinine (P = 0.012), lower lactate dehydrogenase (P = 0.001) and higher platelet count (P = 0.002). The BMI level was 20.78 ± 3.15 in patients without pneumonia compared with the patients with pneumonia (23.81 ± 3.49, P = 0.001). For patients without ARDS, an average BMI level of 22.65 ± 3.53 was observed, significantly lower than patients with ARDS (24.57 ± 3.59, P = 0.022). The mean BMI was 22.35 ± 3.56 in patients experienced with relieving the clinical symptoms or stable condition by radiographic tests, lower than patients with disease exacerbation with 24.89 ± 3.17 (P = 0.001). In addition, lymphocyte count (r = − 0.23, P = 0.027) and platelet count (r = − 0.44, P < 0.001) were negatively correlated with BMI. While hemoglobin (r = 0.267, P = 0.008), creatine kinase (r = 0.331, P = 0.001), serum creatinine (r = 0.424, P < 0.001) and lactate dehydrogenase (r = 0.343, P = 0.001) were significantly positive correlated with BMI. Multivariate analysis showed that older age (OR = 1.046, P = 0.009) and BMI ≥ 24 (OR = 1.258, P = 0.005) were independent risk factors associated ICU admission while BMI ≥ 24 (OR = 4.219, P = 0.007) was independent risk factor associated with radiographic disease exacerbation. CONCLUSIONS: Our study found BMI was significantly associated with clinical manifestations and prognosis of patients with SARS-CoV-2 infection. For patients with increased risk, clinicians should intervene promptly to avoid disease progression.


title: Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV

text: Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10.


title: Report from the World Health Organization’s third Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 8–10th June 2016

text: The third meeting of WHO’s Product Development for Vaccines Advisory Committee (PDVAC) was held in June 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. Since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase III trials of a respiratory syncytial virus (RSV) vaccine candidate has started in the elderly and pregnant women. In addition, PDVAC has also supported vaccine development efforts against important emerging pathogens, including Middle Eastern Coronavirus (MERS CoV) and Zika virus. Trials of HIV and tuberculosis vaccine candidates are steadily progressing towards pivotal data points, and the leading norovirus vaccine candidate has entered a phase IIb efficacy study. WHO’s Immunization, Vaccine and Biologicals (IVB) department is actively working in several pathogen areas on the recommendation of PDVAC, as well as continuing horizon scanning for advances in the development of vaccines that may benefit low and middle income countries (LMICs), such as the recent licensure of the enterovirus 71 (EV71) vaccine in China. Following on from discussions with WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization, PDVAC will also look beyond licensure and consider data needs for vaccine recommendation and implementation to reduce the delay between vaccine approval and vaccine impact.


title: In-silico screening for anti-Zika virus phytochemicals

text: Abstract Zika virus (ZIKV) is an arbovirus that has infected hundreds of thousands of people and is a rapidly expanding epidemic across Central and South America. ZIKV infection has caused serious, albeit rare, complications including Guillain–Barré syndrome and congenital microcephaly. There are currently no vaccines or antiviral agents to treat or prevent ZIKV infection, but there are several ZIKV non-structural proteins that may serve as promising antiviral drug targets. In this work, we have carried out an in-silico search for potential anti-Zika viral agents from natural sources. We have generated ZIKV protease, methyltransferase, and RNA-dependent RNA polymerase using homology modeling techniques and we have carried out molecular docking analyses of our in-house virtual library of phytochemicals with these protein targets as well as with ZIKV helicase. Overall, 2263 plant-derived secondary metabolites have been docked. Of these, 43 compounds that have drug-like properties have exhibited remarkable docking profiles to one or more of the ZIKV protein targets, and several of these are found in relatively common herbal medicines, suggesting promise for natural and inexpensive antiviral therapy for this emerging tropical disease.


title: COVID-19 pandemic persuaded lockdown effects on environment over stone quarrying and crushing areas

text: Abstract Stone quarrying and crushing spits huge stone dust to the environment and causes threats to ecosystem components as well as human health. Imposing emergency lockdown to stop infection of COVID 19 virus on 24.03.2020 in India has created economic crisis but it has facilitated environment to restore its quality. Global scale study has already proved the qualitative improvement of air quality but its possible impact at regional level is not investigated yet. Middle catchment of Dwarka river basin of Eastern India is well known for stone quarrying and crushing and therefore the region is highly polluted. The present study has attempted to explore the impact of forced lockdown on environmental components like Particulate matter (PM) 10, Land surface temperature (LST), river water quality, noise using image and field derived data in pre and during lockdown periods. Result clearly exhibits that Maximum PM10 concentration was 189 to 278 μg/m3 in pre lockdown period and it now ranges from 50 to 60 μg/m3 after 18 days of the commencement of lockdown in selected four stone crushing clusters. LST is reduced by 3–5 °C, noise level is dropped to <65dBA which was above 85dBA in stone crusher dominated areas in pre lockdown period. Adjacent river water is qualitatively improved due to stoppage of dust release to the river. For instance, total dissolve solid (TDS) level in river water adjacent to crushing unit is attenuated by almost two times. When entire world is worried about the appropriate policies for abating environmental pollution, this emergency lockdown shows an absolute way i.e. pollution source management may restore environment and ecosystem with very rapid rate.


title: We Cannot Do It Alone The Intersection of Public Health, Public Policy, and Clinical Microbiology

text: Infectious diseases by definition spread and therefore have impact beyond local hospitals and institutions where they occur. With increasingly complex and worrisome infectious disease evolution including emergence of multidrug resistance, regional, national, and international agencies and resources must work hand in hand with local clinical microbiology laboratories to address these global threats. Described are examples of such resources, both existing and aspirational, that will be needed to address the infectious disease challenges ahead. The authors comment on several instances of entrenched policy that are nonproductive and may be worthy of revision to address unmet needs in infectious disease diagnostics.


How the Islands of the South Pacific have remained relatively unscathed in the midst of the COVID-19 pandemic


Of epidemic proportions: physicians, personal risk, and public trust.


title: Virus neutralising activity of African fruit bat (Eidolon helvum) sera against emerging lyssaviruses

text: Abstract It is likely that phylogroup 2 lyssaviruses circulate within bat reservoirs. We adapted a pseudotype (pt) neutralisation assay (PNA) to a multiplex format enabling serosurveillance for Lagos bat virus (LBV), Mokola virus (MOKV) and West Caucasian bat virus (WCBV) in a potential reservoir, the African straw-coloured fruit bat, Eidolon helvum. Highly correlated titres were observed between single and multiplex PNAs using ptLBV and ptMOKV (r =0.97, p <0.0001), validating its use for bat serosurveillance. Of the bat serum samples screened 56% neutralised ptLBV, 27% ptMOKV and 1% ptWCBV. Mean VNAb titres were 1:266, 1:35 and 1:7 against ptLBV, ptMOKV and ptWCBV respectively. The high seroprevalence estimates suggest that the infection rate of LBV in E. helvum remains high enough to persist in this species. This supports the hypothesis that LBV is endemic in Ghanaian E. helvum and we speculate that LBV may have co-evolved with African megachiroptera.


title: Attenuation of highly pathogenic porcine reproductive and respiratory syndrome virus by inserting an additional transcription unit

text: Transcription regulatory sequences (TRSs) play a key role in the synthesis of porcine reproductive and respiratory syndrome virus (PRRSV) subgenomic mRNAs, which resembles similarity-assisted RNA recombination. In this study, genome instability was found when a highly pathogenic PRRSV (HP-PRRSV) strain was inserted by an additional transcription unit in which a foreign gene GFP was expressed from TRS2 while a copy of TRS6 drove ORF2a/b transcription. Structural protein gene-deleted genomes resulted from enhanced RNA recombinations were identified in the recombinant virus rHV-GFP. Moreover, rHV-GFP replicated slower than parental viruses, and caused less cell death in porcine alveolar macrophages. Pigs infected with rHV-GFP survived with no or mild syndromes, whereas all pigs infected with parental viruses died within 12 days. Our data showed that additional transcription unit insertion could confer genome instability and attenuation of HP-PRRSV.


title: Identification of two novel Rotavirus A genotypes, G35 and P[50], from Peruvian alpaca faeces

text: Abstract Rotavirus A (RVA) Alp11B was detected from a neonatal Peruvian alpaca presenting with diarrhea, and the Alp11B VP7, VP4, VP6, NSP4, and NSP5 genes were sequenced. The partial genotype constellation of this strain, RVA/Alpaca-wt/PER/Alp11B/2010, was determined to be G35-P[50]-I13-E16-H6.


title: Influenza and Other Respiratory Viruses Involved in Severe Acute Respiratory Disease in Northern Italy during the Pandemic and Postpandemic Period (2009–2011)

text: Since 2009 pandemic, international health authorities recommended monitoring severe and complicated cases of respiratory disease, that is, severe acute respiratory infection (SARI) and acute respiratory distress syndrome (ARDS). We evaluated the proportion of SARI/ARDS cases and deaths due to influenza A(H1N1)pdm09 infection and the impact of other respiratory viruses during pandemic and postpandemic period (2009–2011) in northern Italy; additionally we searched for unknown viruses in those cases for which diagnosis remained negative. 206 respiratory samples were collected from SARI/ARDS cases and analyzed by real-time RT-PCR/PCR to investigate influenza viruses and other common respiratory pathogens; also, a virus discovery technique (VIDISCA-454) was applied on those samples tested negative to all pathogens. Influenza A(H1N1)pdm09 virus was detected in 58.3% of specimens, with a case fatality rate of 11.3%. The impact of other respiratory viruses was 19.4%, and the most commonly detected viruses were human rhinovirus/enterovirus and influenza A(H3N2). VIDISCA-454 enabled the identification of one previously undiagnosed measles infection. Nearly 22% of SARI/ARDS cases did not obtain a definite diagnosis. In clinical practice, great efforts should be dedicated to improving the diagnosis of severe respiratory disease; the introduction of innovative molecular technologies, as VIDISCA-454, will certainly help in reducing such “diagnostic gap.”


title: Development of robust in vitro RNA-dependent RNA polymerase assay as a possible platform for antiviral drug testing against dengue

text: Abstract NS5 is the largest and most conserved protein among the four dengue virus (DENV) serotypes. It has been the target of interest for antiviral drug development due to its major role in replication. NS5 consists of two domains, the N-terminal methyltransferase domain and C-terminal catalytic RNA-dependent RNA polymerase (RdRp) domain. It is an unstable protein and is prone to inactivation upon prolonged incubation at room temperature, thus affecting the inhibitor screening assays. In the current study, we expressed and purified DENV RdRp alone in Esherichia coli (E. coli) cells. The N-terminally His-tagged construct of DENV RdRp was transformed into E. coli expression strain BL-21 (DE3) pLysS cells. Protein expression was induced with isopropyl-β-D-thiogalactopyranoside (IPTG) at a final concentration of 0.4mM. The induced cultures were then grown for 20h at 18°C and cells were harvested by centrifugation at 6000xg for 15min at 4°C. The recombinant protein was purified using HisTrap affinity column (Ni-NTA) and then the sample was subjected to size exclusion chromatography, which successfully removed the degradation product obtained during the previous purification step. The in vitro polymerase activity of RdRp was successfully demonstrated using homopolymeric polycytidylic acid (poly(rC)) RNA template. This study describes the high level production of enzymatically active DENV RdRp protein which can be used to develop assays for testing large number of compounds in a high-throughput manner. RdRp has the de novo initiation activity and the in vitro polymerase assays for the protein provide a platform for highly robust and efficient antiviral compound screening systems.


title: Meta-analysis of Relation of Creatine kinase-MB to Risk of Mortality in Coronavirus Disease 2019 Patients

text: Recently, several emerging papers have focused on the association of the creatine kinase-MB (CK-MB) levels with the risk of mortality in infected coronavirus disease 2019 (COVID-19) patients. However, the conclusions are inconsistent. In order to obtain a definitive conclusion on the association between the levels of CK-MB and the risk of mortality in COVID-19 patients, a quantitative meta-analysis was conducted on the basis of published data. Chinese National Knowledge Infrastructure, Web of Science and PubMed databases were extensively searched. Five studies performed in China were finally included in this meta-analysis. The overall results showed that higher levels of CK-MB were significantly associated with an increased risk of the mortality in COVID-19 infected patients (SMD 0.99; 95% CI 0.57 to 1.42; P < 0.001). In conclusion, the elevated CK-MB levels were a crucial characteristic of the mortality of COVID-19 patients.


title: Outcome of Oncology Patients Infected With Coronavirus

text: PURPOSE: This study investigated the features of oncology patients with confirmed Middle East respiratory syndrome (MERS) at the Ministry of National Guard Health Affairs-Riyadh during the outbreak of June 2015 to determine the clinical course and outcome of affected patients. METHODS: The patients’ demographic information, cancer history, treatment pattern, information about MERS-coronavirus (CoV) infection, history of travel, clinical symptoms, test results, and outcome were collected and analyzed as part of a quality improvement project to improve the care and safety of our patients. Only patients with confirmed infection were included. RESULTS: A total of 19 patients were identified, with a median age of 66 years (range, 16-88 years), and 12 patients (63%) were males. The most common underlying disease was hematologic malignancies (47.4%), followed by colorectal cancer (21%) and lung cancer (15.8%). Hypertension and diabetes mellitus were the most common comorbidities (57.9% and 52.6%, respectively). Infection was diagnosed by nasopharyngeal swab in all patients. All patients contracted the infection during their hospitalization for other reasons. Sixteen patients (80%) were admitted to the intensive care unit; 13 patients (81%) had acute respiratory distress syndrome, 11 were intubated (68.75%), 9 had acute renal injury (56.25%), and 3 required dialysis (18.75%). Only 3 patients (15.8%) with early-stage cancers survived. Patients with hematologic malignancies and advanced solid tumors had a 100% case fatality rate. The majority of the causes of death were due to multi-organ failure and septic shock. CONCLUSION: MERS-CoV infection resulted in a high case fatality rate in patients with malignancy. Therefore, it is critical to implement effective primary preventive measures to avoid exposure of patients with cancer to the virus.


title: Memory in Retroviral Quasispecies: Experimental Evidence and Theoretical Model for Human Immunodeficiency Virus

text: Abstract Viral quasispecies may possess a molecular memory of their past evolutionary history, imprinted on minority components of the mutant spectrum. Here we report experimental evidence and a theoretical model for memory in retroviral quasispecies in vivo. Apart from replicative memory associated with quasispecies dynamics, retroviruses may harbour a “cellular” or “anatomical” memory derived from their integrative cycle and the presence of viral reservoirs in body compartments. Three independent sets of data exemplify the two kinds of memory in human immunodeficiency virus type 1 (HIV-1). The data provide evidence of re-emergence of sequences that were hidden in cellular or anatomical compartments for extended periods of infection, and recovery of a quasispecies from pre-existing genomes. We develop a three-component model that incorporates the essential features of the quasispecies dynamics of retroviruses exposed to selective pressures. Significantly, a numerical study based on this model is in agreement with the experimental data, further supporting the existence of both replicative and reservoir memory in retroviral quasispecies.


title: A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector

text: Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.


title: In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect

text: Abstract Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.


title: Nanomaterial-based Aptamer Sensors for Analysis of Illicit Drugs and Evaluation of Drugs Consumption for Wastewater-Based Epidemiology

text: The abuse of illicit drugs usually associated with dramatic crimes may cause significant problems for the whole society. Wastewater-based epidemiology (WBE) has been demonstrated to be a novel and cost-effective way to evaluate the abuse of illicit drugs at the community level, and has been used as a routine method for monitoring and played a significant role for combating the crimes in some countries, e.g. China. The method can also provide temporal and spatial variation of drugs of abuse. The detection methods mainly remain on the conventional liquid chromatography coupled with mass spectrometry, which is extremely sensitive and selective, however needs advanced facility and well-trained personals, thus limit it in the lab. As an alternative, sensors have emerged to be a powerful analytical tool for a wide spectrum of analytes, in particular aptamer sensors (aptasensors) have attracted increasing attention and could act as an efficient tool in this field due to the excellent characteristics of selectivity, sensitivity, low cost, miniaturization, easy-to-use, and automation. In this review, we will briefly introduce the context, specific assessment process and applications of WBE and the recent progress of illicit drug aptasensors, in particular focusing on optical and electrochemical sensors. We then highlight several recent aptasensors for illicit drugs in new technology integration and discuss the feasibility of these aptasensor for WBE. We will summarize the challenges and propose our insights and opportunity on aptasensor for WBE to evaluate community-wide drug use trends and public health.


title: Pedagogical promise and problems: Teaching public health law

text: Summary This article considers the case for teaching public health law as a distinct subject of study within the academic curriculum. It offers proposals on syllabus design, assessment and objectives by reference to the authors' own teaching experience, and also seeks to serve as a resource for those considering the introduction of a course in this field. There is consideration of the conceptual analysis of public health law, and an exploration of the obstacles and opportunities involved in teaching public health law in higher education. To date, issues of public health law have received coverage, if at all, almost exclusively in the context of existing medical or healthcare law modules. Although difficult obstacles remain to be surmounted before the subject can be fully embraced, its marginalization appears to be increasingly misplaced in light of growing awareness of the policy challenges presented by public health and the potential for law to function as a valuable tool to assist in addressing such challenges. There are also potent pedagogical arguments for the teaching of public health law on a liberal academic curriculum.


docid: qjtifwhd

title: Molecular characterization of US-like and Asian non-S INDEL strains of porcine epidemic diarrhea virus (PEDV) that circulated in Japan during 2013–2016 and PEDVs collected from recurrent outbreaks

text: BACKGROUND: Since late 2013, porcine epidemic diarrhea virus (PEDV) has reemerged in Japan and caused severe economic losses to the swine industry. Although PEDV vaccines have been used widely, the disease has swept rapidly across the county, and is commonly observed in PED-vaccinated farms, and has recurred in domestic herds. To better understand PEDVs responsible for the reemerging outbreaks in Japan, full-length spike (S), membrane (M), and nucleocapsid (N) genes of 45 PEDVs collected in Japan during 2013–2016, were sequenced and analyzed. RESULTS: Phylogenetic analysis based on S gene sequences revealed that all the recent field PEDVs were genetically distinct from the classical Japanese strains, and were classified into three genotypes: North American (NA), S INDEL, and Asian non-S INDEL. Our data suggested a possibility that multiple parental PEDV strains were introduced into Japan from abroad at the same time or similar times. The newly identified Japanese strains showed the closest relationship to the US strains. Two sublineages of Japanese strains circulating in Japan were similar to two sublineages identified in the US, suggesting common ancestors for these strains. In comparison with two vaccine strains used in Japan, the field strains had various changes in epitope regions, glycosylation sites, and phosphorylation sites. These substitutions, particularly observed in epitope regions of the S (521, 553, 568, and 570), M (5), and N (123, 252, and 255) proteins, may have affected antigenicity and vaccine efficacy, resulting in an unsuccessful PEDV control. Sequence comparisons between PEDVs collected from primary and secondary outbreaks in three herds revealed that the disease has developed to an endemic stage in which PEDV could persist for nearly two years in the herds or local regions, causing subsequent epidemics. CONCLUSIONS: These results elucidate the genetic characteristics, origin, and molecular epidemiology of PEDVs circulating in Japan, as well as the PEDV strains causing recurrent outbreaks. This study provides a better insight into the PEDVs responsible for recent outbreaks in Japan, and could potentially help to develop measures for controlling and preventing the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1409-0) contains supplementary material, which is available to authorized users.


title: The Major Product of Porcine Transmissible Gastroenteritis Coronavirus Gene 3b Is an Integral Membrane Glycoprotein of 31 kDa

text: Abstract The open reading frame potentially encoding a polypeptide of 27.7 kDa and located as the second of three ORFs (gene 3b) between the S and M genes in the genome of the Purdue strain of porcine transmissible gastroenteritis coronavirus (TGEV) was cloned and expressedin vitroto examine properties of the protein. Gene 3b has a postulated role in pathogenesis, but its truncated form in some laboratory-passaged strains of TGEV has led to the suggestion that it is not essential for virus replication. During synthesisin vitroin the presence of microsomes, the 27.7-kDa polypeptide became an integral membrane protein, retained its postulated hydrophobic N-terminal signal sequence, and underwent glycosylation on apparently two asparagine linkage sites to attain a final molecular mass of 31 kDa. A 20-kDa N-terminally truncated, nonglycosylated, nonanchored form of the protein was also made via an unknown mechanism. The existence of both transmembrane and soluble forms of the gene 3 product in the cell is suggested by immunofluorescence patterns showing both a punctated perinuclear and diffuse intracytoplasmic distribution. No gene 3b product was found on gradient-purified Purdue TGEV by a Western blotting procedure that would have detected as few as 4 molecules/virion, indicating the protein probably is not a structural component of the virion.


title: A global treatments for coronaviruses including COVID‐19

text: In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019‐nCoV). So far, there are no specific treatments for patients with coronavirus disease‐19 (COVID‐19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome‐related coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID‐19. Cathepsin L is required for entry of the 2019‐nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin‐converting‐enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID‐19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019‐nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS‐CoV disease and can be useful for patients of COVID‐19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS‐CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS‐CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID‐19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.


title: Outcome of critically ill patients with influenza virus infection

text: Abstract Background Influenza is a major cause of morbidity and mortality, with its greatest burden on the elderly and patients with chronic co-morbidities in the intensive care unit (ICU). An accurate prognosis is essential for decision-making during pandemic as well as interpandemic periods. Methods A retrospective cohort study was conducted to determine prognostic factors influencing short term outcome of critically ill patients with confirmed influenza virus infection. Baseline characteristics, laboratory and diagnostic findings, ICU interventions and complications were abstracted from medical records using standard definitions and compared between hospital survivors and non-survivors with univariate and multivariate logistic regression analyses. Results 111 patients met the inclusion criteria. Acute respiratory distress syndrome (ARDS) complicated ICU course in 25 (23%) of the patients, with mortality rate of 52%. Multivariate logistic regression analysis identified the following predictors of hospital mortality: Acute Physiology and Chronic Health Evaluation (APACHE) III predicted mortality (Odds ratio [OR] 1.49, 95% confidence interval [CI] 1.1–2.1 for 10% increase), ARDS (OR 7.7, 95% CI 2.3–29) and history of immunosuppression (OR 7.19, 95% CI 1.9–28). Conclusions APACHE III predicted mortality, the development of ARDS and the history of immunosuppression are independent risk factors for hospital mortality in critically ill patients with confirmed influenza virus infection.


SARS-CoV-2, “common cold” coronaviruses’ cross-reactivity and “herd immunity”: The razor of Ockham (1285-1347)?


title: General Surgery chief residents’ perspective on surgical education during the COVID-19 pandemic

text: BACKGROUND: The COVID-19 pandemic has negatively affected the training of general surgery chief residents during the last trimester of their residency. Our goal was to evaluate the educational concerns of graduating general surgery chief residents during the COVID-19 pandemic. METHODS: An anonymous web-based survey was distributed between March 31 and April 7, 2020 to all current general surgery chief residents from six academic medical centers in Boston, MA. Interviews were also conducted with attending surgeons from participating institutions. RESULTS: A total of 24 of 39 General Surgery chief residents participated in our survey (61.5% response rate). General surgery chief residents were most concerned about the potential delay in the date of board exams, followed by not feeling adequately prepared for the board exams, and a possible delay in the graduation date. While not having enough cases to feel ready for fellowship or job, and not achieving a sufficient number of cases to meet the requirements for graduation were only moderately concerning to chief residents, attending surgeons stressed a greater importance on the loss of the operative experience as nearly all (93.3%) of them suggested a personalized approach for additional general surgery training during fellowship or job onboarding. CONCLUSION: In addition to the dramatic impact on public health, the COVID-19 outbreak has also caused unprecedented changes to surgical education. Therefore, creative interventions are needed to help general surgery chief residents successfully transition into the next phase of their surgical career.


title: On services research and education

text: The importance of the services sector can not be overstated; it employs 82.1 percent of the U. S. workforce and 69 percent of graduates from an example technological university. Yet, university research and education have not followed suit. Clearly, services research and education deserve our critical attention and support since services — and services innovation — serve as an indispensable engine for global economic growth. The theme of this paper is that we can and should build services research and education on what has occurred in manufacturing research (especially in regard to customization and intellectual property) and education; indeed, services and manufactured goods become indistinguishable as they are jointly co-produced in real-time. Fortunately, inasmuch as manufacturing concepts, methodologies and technologies have been developed and refined over a long period of time (i.e., since the 1800s), the complementary set of concepts, methodologies and technologies for services are more obvious. However, while new technologies (e.g., the Internet) and globalization trends have served to enable, if not facilitate, services innovation, the same technologies (e.g., the Internet) and 21st Century realities (e.g., terrorism) are making services innovation a far more complex problem and, in fact, may be undermining previous innovations in both services and manufacturing. Finally, there is a need to define a “knowledge-adjusted” GDP metric that can more adequately measure the growing knowledge economy, one driven by intangible ideas and services innovation.


title: Probiotics: Considerations for Human Health

text: Evidence for the role of probiotics in maintenance of health or prevention of disease is mounting and is supported in some cases by blinded, placebo‐controlled human trials. Today, in an era of antibiotic‐resistant pathogens and other looming microbial threats, the value of prevention of infection is recognized. Probiotics may play an important role in helping the body protect itself from infection, especially along the colonized mucosal surfaces of the gastrointestinal tract. Probiotic products are available in many different forms worldwide, including pills, powders, foods, and infant formula. In some cases, general health claims are made that cannot be substantiated for the specific strains and levels being used and consumers must therefore beware.


title: Antiviral T-cell therapy

text: Serious viral infections are a common cause of morbidity and mortality after allogeneic stem cell transplantation. They occur in the majority of allograft recipients and are fatal in 17–20%. These severe infections may be prolonged or recurrent and add substantially to the cost, both human and financial, of the procedure. Many features of allogeneic stem cell transplantation contribute to this high rate of viral disease. The cytotoxic and immunosuppressive drugs administered pre-transplant to eliminate the host hematopoietic/immune system and any associated malignancy, the delay in recapitulating immune ontogeny post-transplant, the immunosuppressive drugs given to prevent graft versus host disease (GvHD), and the effects of GvHD itself, all serve to make stem cell transplant recipients vulnerable to disease from endogenous (latent) and exogenous (community) viruses, and to be incapable of controlling them as quickly and effectively as most normal individuals.


African green monkey model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection


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title: Current Management of Acute Bacterial Rhinosinusitis and the Role of Moxifloxacin

text: Episodes of acute rhinosinusitis are common among adults and are associated with a significant amount of morbidity. The symptoms of rhinosinusitis are nasal drainage, congestion, and sinus pressure. A bacterial sinus infection is more likely if these symptoms worsen after 5–7 days or do not improve after 10–14 days. The majority of bacterial episodes have been associated with Streptococcus pneumoniae and Haemophilus influenzae. In the current era of increasing resistance to β-lactams and macrolides, treatment guidelines have been formulated worldwide to assist clinicians in the selection of antibacterials. According to one model, the following antibacterials are most likely to provide desired outcomes (90%–92% predicted clinical efficacy) for adults: respiratory fluoroquinolones (i.e., moxifloxacin, gatifloxacin, and levofloxacin), ceftriaxone, and high-dose amoxicillin-clavulanate (4 g of amoxicillin/day and 250 mg of clavulanate/day). Although the role of the fluoroquinolones in the treatment of this condition is evolving, fluoroquinolones are often recommended as second-line therapy or as first-line therapy for selected patients (e.g., those who received antibacterials in the previous 4–6 weeks or adults with moderate-to-severe disease).


title: A rapid RT-PCR method to differentiate six established genotypes of rabies and rabies-related viruses using TaqMan™ technology

text: Abstract A rapid and sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay incorporating TaqMan™ probes has been developed that can distinguish among the six established rabies and rabies-related virus genotypes. TaqMan™ probes were designed and validated against 106 rabies and rabies-related virus isolates, one isolate of the Australian bat Lyssaviruses (genotype 7), and 18 other non-rabies viruses important in the veterinary field. The N gene was used as the target for the probes as it is well conserved and has been intensively used to genotype rabies isolates. Additionally, it was found to contain regions specific to each genotype conducive to probe design. The RT-PCR assay described amplifies a portion of the nucleoprotein gene of all 107 rabies and rabies-related viruses, but none of the other viruses tested. Inclusion of TaqMan™-genotype-specific probes in the RT-PCR assay permits rapid identification of the virus present. By combining RT-PCR with TaqMan™ genotyping probes suspect rabies virus isolates can be identified in a single closed tube system that prevents potential PCR-product carry over contamination.


title: Processes of care for community-acquired pneumonia

text: Clinical and economic outcomes in hospitalized patients with CAP directly are related to the way that certain processes of care are executed at the local-hospital level. For each process of care, a clear and evidence-based recommended course of action should be stated. Having an unambiguous action plan helps to develop process-of-care indicators and to educate healthcare workers. Improving processes of care is a secure way to improve outcomes in hospitalized patients with CAP.


title: Recommendations for the Operation of Endoscopy Centers in the setting of the COVID19 pandemic – A WEO guidance document

text: SARS‐CoV‐2 (Severe Acute Respiratory Syndrome Corona Virus 2) is the etiologic agent causing the disease COVID‐19(Corona Virus Disease 19), resulting in a worldwide pandemic. Non emergent endoscopy services have been disrupted as incidence and hospitalizations were rising. It is anticipated that the peak incidence may be leveling off in many parts of the world, but there is a concern for resurgence of the virus activity. Thus, it is important for endoscopy units to have plans in place during peak times of the epidemic and when resuming endoscopic services as the pandemic wanes. The global endoscopy community is faced with the challenge of providing care during this time. The WEO‐COVID guidance task force has provided this resource document based on the current evidence and consensus opinion. These WEO recommendations are meant to guide endoscopists worldwide, should be interpreted in light of specific clinical conditions and resource availability and may not apply in all situations. This guidance document does not supersede the need to check for all local regulations and legislations.


title: Host cell proteases: critical determinants of coronavirus tropism and pathogenesis

text: Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.


title: The characteristics of the synonymous codon usage in enterovirus 71 virus and the effects of host on the virus in codon usage pattern

text: Abstract To give a new perspective on the evolutionary characteristics shaping the genetic diversity of enterovirus 71 (EV71) and the effects of natural selection from its host on the codon usage pattern of the virus, the relative synonymous codon usage (RSCU) values, codon usage bias (CUB) values, effective number of codons (ENCs) values and nucleotide contents were calculated to implement a comparative analysis to evaluate the dynamics of the virus evolution. The characteristics of the synonymous codon usage patterns and nucleotide contents of EV71 and the comparison between ENC values for the whole coding sequence of EV71 and that of coding sequences for viral proteins of EV71 all indicate that the interaction between mutation pressure from virus and natural selection from host exists in the processes of evolution of EV71. The synonymous codon usage pattern of EV71 is a mixture of coincidence and antagonism to that of host cell. In addition, the genetic diversity of EV71 strains and the preferential selection of some synonymous codons in EV71 strains based on the different epidemic areas were observed, suggesting that geographic and social factors may play roles in influencing the evolution of this virus.


title: Sexually Transmitted Infections during the COVID‐19 outbreak: comparison of patients referring to the service of sexually transmitted diseases during the sanitary emergency with those referring during the common practice

text: Sexually transmitted infections (STIs) and diseases (STDs) affect millions of people every year worldwide(1). In Italy, data are provided by the Italian National Institute of Health (INIH) and reported to the European Centre for Disease Prevention and Control (ECDC)(2,3). In 1991 and 2009 the Italian sentinel surveillance system was established, consisting in 25 public centers (12 clinical, 13 laboratories) on the national field for diagnosis, treatment and data transmission to the INIH(4). The STDs service of Dermatology, Bologna belongs to it and is a free‐access service (7.30‐11 am) from Monday to Friday, with a patient flow of 50 patients/day.


title: Tandem Placement of a Coronavirus Promoter Results in Enhanced mRNA Synthesis from the Downstream-Most Initiation Site

text: Abstract Insertion of the 17-nucleotide promoter region for the bovine coronavirus N gene as part of a 27-nucleotide cassette into the open reading frame of a cloned synthetic defective-interfering (DI) RNA resulted in synthesis of subDI RNA transcripts from the replicating DI RNA genome. Duplicating and triplicating the promoter sequence in tandem caused a progressive increase in the efficiency of subgenomic mRNA synthesis despite a concurrent decrease in the rate of DI RNA accumulation that was not specific to the promoter sequences being added. Although initiation of transcription (leader fusion) occurred at each of the three promoter sites in the tandem construct, almost all of the transcripts were found as a product of the most downstream (3′-most on the genome) promoter. These results show that enhancement of subgenomic mRNA synthesis is a property that can reside within sequence situated near the promoter. A possible role for the plus strand in the downstream promoter choice is suggested.


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title: Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis

text: Abstract Background An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 and triggered a Public Health Emergency of International Concern (PHEIC). We aimed to find risk factors for the progression of COVID-19 to help reducing the risk of critical illness and death for clinical help. Methods The data of COVID-19 patients until March 20, 2020 were retrieved from four databases. We statistically analyzed the risk factors of critical/mortal and non-critical COVID-19 patients with meta-analysis. Results Thirteen studies were included in Meta-analysis, including a total number of 3027 patients with SARS-CoV-2 infection. Male, older than 65, and smoking were risk factors for disease progression in patients with COVID-19 (male: OR = 1.76, 95% CI (1.41, 2.18), P < 0.00001; age over 65 years old: OR =6.06, 95% CI(3.98, 9.22), P < 0.00001; current smoking: OR =2.51, 95% CI(1.39, 3.32), P = 0.0006). The proportion of underlying diseases such as hypertension, diabetes, cardiovascular disease, and respiratory disease were statistically significant higher in critical/mortal patients compared to the non-critical patients (diabetes: OR=3.68, 95% CI (2.68, 5.03), P < 0.00001; hypertension: OR = 2.72, 95% CI (1.60,4.64), P = 0.0002; cardiovascular disease: OR = 5.19, 95% CI(3.25, 8.29), P < 0.00001; respiratory disease: OR = 5.15, 95% CI(2.51, 10.57), P < 0.00001). Clinical manifestations such as fever, shortness of breath or dyspnea were associated with the progression of disease [fever: 0R = 0.56, 95% CI (0.38, 0.82), P = 0.003;shortness of breath or dyspnea: 0R=4.16, 95% CI (3.13, 5.53), P < 0.00001]. Laboratory examination such as aspartate amino transferase(AST) > 40U/L, creatinine(Cr) ≥ 133mol/L, hypersensitive cardiac troponin I(hs-cTnI) > 28pg/mL, procalcitonin(PCT) > 0.5ng/mL, lactatede hydrogenase(LDH) > 245U/L, and D-dimer > 0.5mg/L predicted the deterioration of disease while white blood cells(WBC)<4 × 109/L meant a better clinical status[AST > 40U/L:OR=4.00, 95% CI (2.46, 6.52), P < 0.00001; Cr ≥ 133μmol/L: OR = 5.30, 95% CI (2.19, 12.83), P = 0.0002; hs-cTnI > 28 pg/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; PCT > 0.5 ng/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001;LDH > 245U/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; D-dimer > 0.5mg/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; WBC < 4 × 109/L: OR = 0.30, 95% CI (0.17, 0.51), P < 0.00001]. Conclusion Male, aged over 65, smoking patients might face a greater risk of developing into the critical or mortal condition and the comorbidities such as hypertension, diabetes, cardiovascular disease, and respiratory diseases could also greatly affect the prognosis of the COVID-19. Clinical manifestation such as fever, shortness of breath or dyspnea and laboratory examination such as WBC, AST, Cr, PCT, LDH, hs-cTnI and D-dimer could imply the progression of COVID-19.


title: Molecular Investigation of SARS–CoV-2 Proteins and Their Interactions with Antiviral Drugs

text: A new Coronavirus strain, named SARS-CoV-2, suddenly emerged in early December 2019. SARS-CoV-2 resulted in being dramatically infectious, with thousands of people infected. In this scenario, and without effective vaccines available, the importance of an immediate tool to support patients and against viral diffusion becomes evident. In this study, we exploit the molecular docking approach to analyze the affinity between different viral proteins and several inhibitors, originally developed for other viral infections. Our data show that, in some cases, a relevant binding can be detected. These findings support the hypothesis to develop new antiviral agents against COVID-19, on the basis of already established therapies.


title: Estudio clínico-epidemiológico de la infección por Bordetella pertussis en la isla de Gran Canaria en el período 2008-2016

text: Resumen Objetivo Describir el patrón epidemiológico y clínico de la infección por Bordetella pertussis (tosferina) en niños menores de un año hospitalizados en un hospital pediátrico de Gran Canaria. Pacientes y métodos Se revisaron retrospectivamente las historias clínicas de los pacientes con diagnóstico microbiológico de infección por B. pertussis mediante reacción en cadena de la polimerasa, de enero de 2008 a diciembre de 2016. Resultados Se identificaron 110 pacientes, de los cuales 105 (95,4%) fueron menores de 6 meses y el 59,1% eran varones. La incidencia anual de hospitalización se estimó entre 13,7 y 425,0 casos por cada 100.000 lactantes menores de 12 meses, con 2picos en 2011 y 2015. Los familiares cercanos fueron las principales fuentes de contagio potenciales. Las principales manifestaciones fueron la tos pertusoide asociada con signos catarrales, cianosis y linfocitosis. El 15,4% de los pacientes presentaron complicaciones (principalmente neumonía), pero la evolución fue favorable en todos los casos. La menor edad y la no vacunación se asociaron con un mayor riesgo de desarrollar complicaciones (p < 0,05). La coinfección viral ocurrió en el 31,6% de los pacientes diagnosticados de infección por B. pertussis. Conclusiones La incidencia de infección por B. pertussis ha aumentado en los últimos años en nuestra área, con un menor desarrollo de complicaciones y con tasas de mortalidad inferiores al período anterior. La menor edad y la no vacunación previa se consideran factores de riesgo para el desarrollo de complicaciones. La vacunación en mujeres embarazadas probablemente disminuirá la incidencia en el futuro, sobre todo en niños menores de 6 meses. Abstract Objective Describe the epidemiological and clinical pattern of Bordetella pertussis infection (whooping cough) among hospitalised infants less than one year-old in a paediatric hospital in Gran Canaria. Patients and methods A retrospective review of the patient hospital records was performed, and recording only those with a microbiological diagnosis of pertussis infection detected using polymerase chain reaction, from January 2008 to December 2016. Results A total of 110 patients were identified, of which 105 (95.4%) were less than 6 months-old, and 59.1% were males. The annual incidence of hospital admissions was estimated between 13.7 to 425.0 cases per 100,000 infants <12 months old, with 2peaks in 2011 and 2015. Household members were the main potential sources of infection. Main clinical features were pertussis cough associated with signs of catarrh, cyanosis, and lymphocytosis. Complications occurred in 15.4% of the patients (mainly pneumonia), but the outcome was favourable in all the cases. A lower age and non-vaccination were associated with an increased risk of developing complications (P<.05). Viral co-infection occurred in 31.6% of infants diagnosed with pertussis. Conclusions The incidence of pertussis has increased in the last years in Gran Canaria, with a lower development of complications and mortality rates compared with the previous period. Lower age and non-vaccination status are considered risk factors for developing complications. Vaccination in pregnant women will probably lead to a decline in the incidence in the future, especially in infants younger than 6 months.


title: Enterovirus 71 protease 2A(pro) and 3C(pro) differentially inhibit the cellular endoplasmic reticulum-associated degradation (ERAD) pathway via distinct mechanisms, and enterovirus 71 hijacks ERAD component p97 to promote its replication

text: Endoplasmic reticulum-associated degradation (ERAD) is an important function for cellular homeostasis. The mechanism of how picornavirus infection interferes with ERAD remains unclear. In this study, we demonstrated that enterovirus 71 (EV71) infection significantly inhibits cellular ERAD by targeting multiple key ERAD molecules with its proteases 2A(pro) and 3C(pro) using different mechanisms. Ubc6e was identified as the key E2 ubiquitin-conjugating enzyme in EV71 disturbed ERAD. EV71 3C(pro) cleaves Ubc6e at Q219G, Q260S, and Q273G. EV71 2A(pro) mainly inhibits the de novo synthesis of key ERAD molecules Herp and VIMP at the protein translational level. Herp differentially participates in the degradation of different glycosylated ERAD substrates α-1 antitrypsin Null Hong Kong (NHK) and the C-terminus of sonic hedgehog (SHH-C) via unknown mechanisms. p97 was identified as a host factor in EV71 replication; it redistributed and co-exists with the viral protein and other known replication-related molecules in EV71-induced replication organelles. Electron microscopy and multiple-color confocal assays also showed that EV71-induced membranous vesicles were closely associated with the endoplasmic reticulum (ER), and the ER membrane molecule RTN3 was redistributed to the viral replication complex during EV71 infection. Therefore, we propose that EV71 rearranges ER membranes and hijacks p97 from cellular ERAD to benefit its replication. These findings add to our understanding of how viruses disturb ERAD and provide potential anti-viral targets for EV71 infection.


title: What makes health systems resilient against infectious disease outbreaks and natural hazards? Results from a scoping review

text: BACKGROUND: The 2014–2016 Ebola outbreak was a wake-up call regarding the critical importance of resilient health systems. Fragile health systems can become overwhelmed during public health crises, further exacerbating the human, economic, and political toll. Important work has been done to describe the general attributes of a health system resilient to these crises, and the next step will be to identify the specific capacities that health systems need to develop and maintain to achieve resiliency. METHODS: We conducted a scoping review of the literature to identify recurring themes and capacities needed for health system resiliency to infectious disease outbreaks and natural hazards and any existing implementation frameworks that highlight these capacities. We also sought to identify the overlap of the identified themes and capacities with those highlighted in the World Health Organization’s Joint External Evaluation. Sources of evidence included PubMed, Web of Science, OAIster, and the websites of relevant major public health organizations. RESULTS: We identified 16 themes of health system resilience, including: the need to develop plans for altered standards of care during emergencies, the need to develop plans for post-event recovery, and a commitment to quality improvement. Most of the literature described the general attributes of a resilient health system; no implementation frameworks were identified that could translate these elements into specific capacities that health system actors can employ to improve resilience to outbreaks and natural hazards in a variety of settings. CONCLUSIONS: An implementation-oriented health system resilience framework could help translate the important components of a health system identified in this review into specific capacities that actors in the health system could work to develop to improve resilience to public health crises. However, there remains a need to further refine the concept of resilience so that health systems can simultaneously achieve sustainable transformations in healthcare practice and health service delivery as well as improve their preparedness for emergencies.


title: Elucidation and Clinical Role of Emerging Viral Respiratory Tract Infections in Children

text: Acute respiratory viral infections (ARVI’s) are the most common infectious disease in humans. With the appearance of molecular techniques the recovery of viruses has dramatically increased. Nowadays virologists can quickly discriminate virological families and related viruses from emerging viruses and consequently identify novel viruses. Many new respiratory viruses have been identified in children in the past 15 years. In this review we shortly discuss novel respiratory viruses and their pathogenic role in pediatric respiratory disease. Advantages and drawbacks of the technique and our current knowledge will be discussed. We will conclude this review with a general discussion on the future role of molecular diagnostic virology in the clinic.


title: Severe bleeding in a patient with Factor XIII deficiency and COVID‐19

text: Since the outbreak in last December of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in Wuhan, China, scientific literature is providing essential contributions to elucidate the pathophysiological and clinical features of the Coronavirus disease 2019 (COVID‐19).(1) Consistent evidence shows that COVID‐19 is associated with significant changes in coagulation laboratory testing, mainly prolonged prothrombin time and elevated D‐dimer.(2)


title: No evidence of SARS‐Cov‐2 infection by PCR or serology in children with pseudochilblain

text: Despite its aggressive clinical course, leading to 6.4% fatality rate as of May 25, 2020 (https://qap.ecdc.europa.eu/public/extensions/COVID-19/COVID-19.html), COVID‐19 turned out to be only marginally aggressive in children. In a report from Lombardy, 18/88 COVID‐19 hospitalized adults (20%) had developed cutaneous manifestations: erythematous rash, widespread urticarial, and chickenpox‐like vesicles. Trunk was the main involved region. Itching was low or absent and usually lesions healed in few days. An unexpected outbreak of acute pseudochilblain skin lesions is being reported from different countries and related to COVID‐19.


title: Neurological manifestations of COVID-19 and other coronaviruses: a systematic review

text: OBJECTIVE: To describe the main neurological manifestations related to coronavirus infection in humans. METHODOLOGY: A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: “coronavirus” or “Sars-CoV-2” or “COVID-19” and “neurologic manifestations” or “neurological symptoms” or “meningitis” or “encephalitis” or “encephalopathy,” following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11% and 12% of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8%), dizziness (57, 13.9%), altered consciousness (46; 11.2%), vomiting (26; 6.3%), epileptic crises (7; 1.7%), neuralgia (5; 1.2%), and ataxia (3; 0.7%). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1%) patients, hypoxic encephalopathy in 23 (5.6%) patients, acute cerebrovascular disease in 6 (1.4%) patients, 1 (0.2%) patient with possible acute disseminated encephalomyelitis, 1 (0.2%) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4%) patients with CoV related to Guillain-Barré syndrome. CONCLUSION: Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.


title: Vaccinia virus proteolysis—a review

text: It is well known that viruses, as obligate intracellular parasites, must use their hosts' metabolic machinery in order to replicate their genomes and form infectious progeny virions. What is less well known are the details of how viruses make sure that once all the necessary proteins are made, that they assume the correct configuration at the proper time in order to catalyse the efficient assembly of infectious virions. One of the methods employed by viruses to regulate this process is the proteolytic cleavage of viral proteins. Over the past several decades, studies in numerous laboratories have demonstrated that morphogenic proteolysis plays a major and essential role during the assembly and maturation of infectious poxvirus virions. In this review we describe the history of vaccinia virus proteolysis as a prototypic viral system. Copyright © 2006 John Wiley & Sons, Ltd.


title: Preparedness of personal protective equipment and implementation of new CPR strategies for patients with out-of-hospital cardiac arrest in the COVID-19 era

text: Abstract Background In February and March 2020, healthcare providers and citizens in Daegu, South Korea, experienced the onslaught of a large-scale community epidemic of COVID-19. This had a profound impact on patients who experienced out-of-hospital cardiac arrest (OHCA). Methods We conducted a retrospective observational study of 171 OHCA patients based on the multicenter WinCOVID registry. Demographic and clinical characteristics, overall survival, COVID-19 related data, as well as personal protective equipment (PPE) and resuscitation techniques used during the COVID-19 outbreak were evaluated and compared with outcomes from a 2018 historical cohort (n=158). Results Among the interventions, high-level PPE was introduced and standard cardiopulmonary resuscitation was changed to chest compressions using mechanical devices. All OHCA patients were treated as confirmed or suspicious for COVID-19 regardless of symptoms. Furthermore, complete or partial closures of emergency centers and the number of medical personnel requiring self-isolation decreased in response to the introduction of isolated resuscitation units. However, the adjusted odds ratio and 95% confidence intervals for survival discharge and favorable neurologic outcome were 0.51 (0.25–0.97) and 0.45 (0.21–1.07) compared with those in the 2018 historical cohort. Conclusions Responses to the COVID-19 pandemic included changes to current PPE strategies and introduction of isolated resuscitation units; the latter intervention reduced the number of unexpected closures and quarantines of emergency resources early on during the COVID-19 outbreak. Given the possibility of future outbreaks, we need to have revised resuscitation strategies and the capacity to commandeer emergency resources for OHCA patients.


title: Reactomes of Porcine Alveolar Macrophages Infected with Porcine Reproductive and Respiratory Syndrome Virus

text: Porcine reproductive and respiratory syndrome (PRRS) has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV), which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression) libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs) produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE) tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM) analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and lays a strong foundation for vaccine development to control PRRS incidence in pigs.


title: Air quality status during 2020 Malaysia Movement Control Order (MCO) due to 2019 novel coronavirus (2019-nCoV) pandemic

text: Abstract An outbreak of respiratory illness which is proven to be infected by a 2019 novel coronavirus (2019-nCoV) officially named as Coronavirus Disease 2019 (COVID-19) was first detected in Wuhan, China and has spread rapidly in other parts of China as well as other countries around the world, including Malaysia. The first case in Malaysia was identified on 25 January 2020 and the number of cases continue to rise since March 2020. Therefore, 2020 Malaysia Movement Control Order (MCO) was implemented with the aim to isolate the source of the COVID-19 outbreak. As a result, there were fewer number of motor vehicles on the road and the operation of industries was suspended, ergo reducing emissions of hazardous air pollutants in the atmosphere. We had acquired the Air Pollutant Index (API) data from the Department of Environment Malaysia on hourly basis before and during the MCO with the aim to track the changes of fine particulate matter (PM2.5) at 68 air quality monitoring stations. It was found that the PM2.5 concentrations showed a high reduction of up to 58.4% during the MCO. Several red zone areas (>41 confirmed COVID-19 cases) had also reduced of up to 28.3% in the PM2.5 concentrations variation. The reduction did not solely depend on MCO, thus the researchers suggest a further study considering the influencing factors that need to be adhered to in the future.


title: Rhino/enteroviruses in hospitalized children: A comparison to influenza viruses

text: Abstract Background The relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown. Objectives This retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus. Study design Respiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review. Results Of the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p <0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p <0.01) with crackles (36.3% vs. 23.3%, p <0.01) and wheezing (41.7% vs. 22.8%, p <0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p <0.01), duration of fever (1 days vs. 3 days, p <0.01), and duration of hypoxemia (2 days vs. 3 days, p <0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired. Conclusions HRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.


title: High-Dose Corticosteroid Use and Risk of Hip Osteonecrosis: Meta-Analysis and Systematic Literature Review

text: Abstract The effect of varying corticosteroid regimens on hip osteonecrosis incidence remains unclear. We performed a meta-analysis and systematic literature review to determine osteonecrosis occurrences in patients taking corticosteroids at varying mean and cumulative doses and treatment durations, and whether medical diagnoses affected osteonecrosis incidence. Fifty-seven studies (23,561 patients) were reviewed. Regression analysis determined significance between corticosteroid usage and osteonecrosis incidence. Osteonecrosis incidence was 6.7% with corticosteroid treatment of >2 g (prednisone-equivalent). Systemic lupus erythematosus patients had positive correlations between dose and osteonecrosis incidence. Each 10 mg/d increase was associated with a 3.6% increase in osteonecrosis rate, and >20 mg/d resulted in a higher osteonecrosis incidence. Clinicians must be wary of osteonecrosis in patients on high corticosteroid regimens, particularly in systematic lupus erythematosus.


title: A multiplex RT-PCR assay for rapid and simultaneous detection of four RNA viruses in swine

text: Abstract A multiplex reverse transcription polymerase chain rection (mRT-PCR) was developed for simultaneous detection of four RNA viruses in swine. The conserved target sequences directed to classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis coronavirus (TGEV) were selected based on alignments of genomic sequences and then specific primers were designed. The mRT-PCR assay was developed and evaluated for its specificity and sensitivity. The expected product from the single viral template was amplified by mRT-PCR and no spurious PCR amplification occurred from the genomic RNA or DNA of other pathogens. For single virus or different combinations of two viruses the detection limit of mRT-PCR was consistent with a single RT-PCR wtith 1 × 103 copies. For different combinations of the three viruses or four viruses, sensitivity of PEDV detection partially decreased. All of positive clinical specimens by the mRT-PCR were identically confirmed using Taqman RT-qPCR. Therefore, the mRT-PCR is a useful tool for epidemiological studies and laboratory diagnosis of single virus and/or mixed infections in swine.


title: Brain oxytocin: how puzzle stones from animal studies translate into psychiatry

text: The neuropeptide oxytocin has attracted great attention of the general public, basic neuroscience researchers, psychologists, and psychiatrists due to its profound pro-social, anxiolytic, and “anti-stress” behavioral and physiological effects, and its potential application for treatment of mental diseases associated with altered socio-emotional competence. During the last decade, substantial progress has been achieved in understanding the complex neurobiology of the oxytocin system, including oxytocinergic pathways, local release patterns, and oxytocin receptor distribution in the brain, as well as intraneuronal oxytocin receptor signaling. However, the picture of oxytocin actions remains far from being complete, and the central question remains: “How does a single neuropeptide exert such pleotropic actions?” Although this phenomenon, typical for many of about 100 identified neuropeptides, may emerge from the anatomical divergence of oxytocin neurons, their multiple central projections, distinct oxytocin-sensitive cell types in different brain regions, and multiple intraneuronal signaling pathways determining the specific cellular response, further basic studies are required. In conjunction, numerous reports on positive effects of intranasal application of oxytocin on human brain networks controlling socio-emotional behavior in health and disease require harmonic tandems of basic researchers and clinicians. During the COVID-19 crisis in 2020, oxytocin research seems central as question of social isolation-induced inactivation of the oxytocin system, and buffering effects of either activation of the endogenous system or intranasal application of synthetic oxytocin need to be thoroughly investigated.


title: Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells

text: Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.


title: Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?

text: Abstract Human metapneumovirus (HMPV) is a recently discovered pathogen first identified in respiratory specimens from young children suffering from clinical respiratory syndromes ranging from mild to severe lower respiratory tract illness. HMPV has worldwide prevalence, and is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to respiratory syncytial virus (RSV). The disease burden associated with HMPV infection has not been fully elucidated; however, studies indicate that HMPV may cause upper or lower respiratory tract illness in patients between ages 2 months and 87 years, may co-circulate with RSV, and HMPV infection may be associated with asthma exacerbation. The mechanisms and effector pathways contributing to immunity or disease pathogenesis following infection are not fully understood; however, given the clinical significance of HMPV, there is a need for a fundamental understanding of the immune and pathophysiological processes that occur following infection to provide the foundation necessary for the development of effective vaccine or therapeutic intervention strategies. This review provides a current perspective on the processes associated with HMPV infection, immunity, and disease pathogenesis.


title: Microarray technology in obstetrics and gynecology: A guide for clinicians

text: Microarrays can be constructed with dozens to millions of probes on their surface to allow high-throughput analyses of many biologic processes to be performed simultaneously on the same sample. Microarrays are now widely used for gene expression analysis, deoxyribonucleic acid resequencing, single-nucleotide polymorphism genotyping, and comparative genomic hybridization. Microarray technology is accelerating research in many fields and now microarrays are moving into clinical application. This review discusses the emerging role of microarrays in molecular diagnostics, pathogen detection, oncology, and pharmacogenomics.


title: Enhancement of blood-brain barrier permeability is required for intravenously administered virus neutralizing antibodies to clear an established rabies virus infection from the brain and prevent the development of rabies in mice

text: Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the Blood–brain Barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans.


title: Rapidly fatal outcome of Covid-19 after successful emergency surgery during pandemic outbreak in Northern Italy

text: INTRODUCTION: A pandemic outbreak of novel coronavirus, named SARS-CoV-2 and responsible of Coronavirus Disease 2019 (COVID-19), has rapidly spread from China to Europe, being Northern Italy the first focus outside Asia. Little is known about the evolution of SARS-CoV-2 infection in patients undergoing surgery. PRESENTATION OF CASE: Here we report the first confirmed case of early postoperative SARS-CoV-2 infection in a patient recovering after Hartmann’s procedure for acute diverticulitis. After an otherwise unevenful postoperative course, on post-operative day 8, the patient suddenly presented hyperpyrexia and cough, rapidly evolving to respiratory failure and death 36 h after symptoms onset. CT-scan identified bilateral, diffuse, interstitial pneumonitis and oropharyngeal swab test confirmed the presence of SARS-CoV-2. A previous contact with the partner, developing the same symptoms, remained unrecognized until ICU admission. DISCUSSION: During a pandemic outbreak, the early identification of SARS-CoV-2 infection of an inside patient initially considered to be infection-free has a pivotal importance not only for the prompt patient’s management, but also to avoid infection spreading to other patients and hospital personnel.In the reported case, a more precise information to the patient regarding the imperative necessity to inform the medical personnel of any person of his entourage presenting, at any time, any tell-tale sign, symptom or examination which may be attributed to COVID-19, may have had allowed to anticipate patient’s isolation and examinations and procedures aimed at identifying such an infection. CONCLUSION: Persistent hyperleucocytosis and increased CRP serum level in spite of uneventful postoperative course were the only, aspecific markers of an ongoing SARS-CoV-2 infection before symptoms’ onset, and should be considered in future clinical practice in order to adopt the prompt and appropriate patient management and limit COVID-19 contagion in surgical units.


title: Lactic acid bacterial colonization and human rotavirus infection influence distribution and frequencies of monocytes/macrophages and dendritic cells in neonatal gnotobiotic pigs

text: Despite accumulating knowledge of porcine macrophages and dendritic cells (DCs) from in vitro studies, information regarding monocytes/macrophages and DCs in lymphoid tissues of enteric pathogen-infected neonatal animals in vivo is limited. In this study we evaluated the influence of commensal bacterial [two strains of lactic acid bacteria (LAB), Lactobacillus acidophilus and L. reuteri] colonization and rotavirus infection on distribution and frequencies of monocytes/macrophages and conventional DCs (cDCs) in ileum, spleen and blood. Gnotobiotic pigs were inoculated with LAB and virulent Wa strain human rotavirus (HRV) (LAB+HRV+), HRV only (LAB−HRV+), LAB only (LAB+HRV−) or mock (LAB−HRV−). The cDCs were characterized as SWC3(+)CD11R1(+), whereas monocytes/macrophages were identified as SWC3(+)CD11R1(−) by flow cytometry in the gnotobiotic pigs at 10 days of age. Infection with HRV alone activated/recruited significantly more monocytes/macrophages to the intestine than LAB colonization and 56% versus 28% of these cells expressed CD14. Colonization with LAB alone also significantly increased the frequencies of monocytes/macrophages and cDCs and the CD14 expression on monocytes/macrophages in ileum and spleen compared to the controls. LAB colonization plus HRV infection significantly reduced macrophage and cDC frequencies in spleen compared to LAB colonization or HRV infection alone, suggesting that LAB colonization down-regulated HRV− infection-induced monocyte/macrophage activation/recruitment at the systemic lymphoid tissue. These results illustrated the distribution of porcine monocytes/macrophages and cDCs and the frequencies of CD14 expression on these cells in intestinal and systemic lymphoid tissues in the early stage of immune responses to intestinal colonization by LAB versus infection by an enteric pathogen HRV and will facilitate further in vivo studies on functional characterization of these immune cells in neonates.


title: Medicine, epidemiology and humanism before and after COVID-19

text: Abstract The rapid propagation of SARS-CoV-2 requires the generation of evidence to help mitigate its global damage. The precise measurement with the appropriate clinical and epidemiological indicators associated with COVID-19 is a necessary step in reducing the individual and population burden of the current pandemic. These unprecedented times have raised a challenge for epidemiologists of chronic diseases and have required a practical approach “to do something to help during this disaster”. The options include returning to clinical care or resorting to online textbooks and resources for accelerated courses on the research of outbreaks. However, being aware of the magnitude of individual suffering endured by so many, including many esteemed and close colleagues, becomes a personal challenge of enormous proportions. The arts and other forms of humanities can help re-establish equilibrium, both during the pandemic and especially after it.


title: Differentially Private Mobile Crowd Sensing Considering Sensing Errors

text: An increasingly popular class of software known as participatory sensing, or mobile crowdsensing, is a means of collecting people’s surrounding information via mobile sensing devices. To avoid potential undesired side effects of this data analysis method, such as privacy violations, considerable research has been conducted over the last decade to develop participatory sensing that looks to preserve privacy while analyzing participants’ surrounding information. To protect privacy, each participant perturbs the sensed data in his or her device, then the perturbed data is reported to the data collector. The data collector estimates the true data distribution from the reported data. As long as the data contains no sensing errors, current methods can accurately evaluate the data distribution. However, there has so far been little analysis of data that contains sensing errors. A more precise analysis that maintains privacy levels can only be achieved when a variety of sensing errors are considered.


title: Global burden of childhood pneumonia and diarrhoea

text: Diarrhoea and pneumonia are the leading infectious causes of childhood morbidity and mortality. We comprehensively reviewed the epidemiology of childhood diarrhoea and pneumonia in 2010–11 to inform the planning of integrated control programmes for both illnesses. We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years. We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death. A high proportion of deaths occurs in the first 2 years of life in both diseases—72% for diarrhoea and 81% for pneumonia. The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc deficiency. Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia. Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.


title: Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

text: Abstract Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulations were carried out to unravel changes in the MERS CoV heptad repeat domains (HRs) and factors affecting fusion state HR stability. Results indicated that HR trimer is more rapidly stabilized, having stable system energy and lower root mean square deviations (RMSDs). While trimers were the predominant active form of CoVs HRs, monomers were also discovered in both of viral and cellular membranes. In order to find the differences between S2 monomer and trimer molecular dynamics, S2 monomer was modelled and subjected to MD simulation. In contrast to S2 trimer, S2 monomer was unstable, having high RMSDs with major drifts above 8 Å. Fluctuation of HR residue positions revealed major changes in the C-terminal of HR2 and the linker coil between HR1 and HR2 in both monomer and trimer. Hydrophobic residues at the a and d positions of HR helices stabilize the whole system, with minimal changes in RMSD. The global distance test and contact area difference scores support instability of MERS CoV S2 monomer. Analysis of HR1-HR2 inter-residue contacts and interaction energy revealed three energy scales along HR helices. Two strong interaction energies were identified at the start of the HR2 helix and at the C-terminal of HR2. The identified critical residues by MD simulation and residues at the a and d positions of HR helix were strong stabilizers of HR recognition.


title: Management of acute bronchitis in healthy adults

text: Acute respiratory infections (ARIs) are the most common infections in humans, accounting for half of all acute conditions each year in the United States. Acute bronchitis episodes represent a significant portion of these illnesses. This article focuses on acute bronchitis in otherwise healthy individuals.