title: Inhibitors of the Influenza A Virus M2 Proton Channel Discovered Using a High-Throughput Yeast Growth Restoration Assay

text: The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.


title: Histopathological and immunohistochemical findings in lymphoid tissues of the endangered Iberian lynx (Lynx pardinus)

text: Abstract The Iberian lynx (Lynx pardinus) is the most threatened wild feline in the world. Little is known about the diseases and pathology that affect this animal. The aim of this study was to evaluate the histopathological status of the peripheral lymphoid tissues and thymus of Iberian lynxes necropsied between 1998 and 2003. Seventeen animals including females (n=8) and males (n=9), age range of 10 months to 16 years, with different causes of death were histopathologically and immunohistochemically (anti-CD3, CD79, MAC387, CD68) studied. Feline immunosuppressive virus laboratorial tests were negative. Five individuals presented neoplasia and/or tuberculosis. All animals presented some degree of both B and T cells depletion in peripheral lymphoid tissues and follicular hyalinosis in the center of depleted follicles. A viral origin of the lymphoid depletion is postulated although other causes (inbreeding, stress, toxic) are not ruled out. The loss of the effectiveness of the immune system increases the vulnerability of the critically endangered Iberian lynx to pathogens.


Author index and Subject index


title: The S2 Subunit of QX-type Infectious Bronchitis Coronavirus Spike Protein Is an Essential Determinant of Neurotropism

text: Some coronaviruses (CoVs) have an extra furin cleavage site (RRKR/S, furin-S2′ site) upstream of the fusion peptide in the spike protein, which plays roles in virion adsorption and fusion. Mutation of the S2′ site of QX genotype (QX-type) infectious bronchitis virus (IBV) spike protein (S) in a recombinant virus background results in higher pathogenicity, pronounced neural symptoms and neurotropism when compared with conditions in wild-type IBV (WT-IBV) infected chickens. In this study, we present evidence suggesting that recombinant IBV with a mutant S2′ site (furin-S2′ site) leads to higher mortality. Infection with mutant IBV induces severe encephalitis and breaks the blood–brain barrier. The results of a neutralization test and immunoprotection experiment show that an original serum and vaccine can still provide effective protection in vivo and in vitro. This is the first demonstration of IBV-induced neural symptoms in chickens with encephalitis and the furin-S2′ site as a determinant of neurotropism.


title: Isolation and molecular characterization of type I and type II feline coronavirus in Malaysia

text: BACKGROUND: Feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV) are two important coronaviruses of domestic cat worldwide. Although FCoV is prevalent among cats; the fastidious nature of type I FCoV to grow on cell culture has limited further studies on tissue tropism and pathogenesis of FCoV. While several studies reported serological evidence for FCoV in Malaysia, neither the circulating FCoV isolated nor its biotypes determined. This study for the first time, describes the isolation and biotypes determination of type I and type II FCoV from naturally infected cats in Malaysia. FINDINGS: Of the total number of cats sampled, 95% (40/42) were RT-PCR positive for FCoV. Inoculation of clinical samples into Crandell feline kidney cells (CrFK), and Feline catus whole fetus-4 cells (Fcwf-4), show cytopathic effect (CPE) characterized by syncytial cells formation and later cell detachment. Differentiation of FCoV biotypes using RT-PCR assay revealed that, 97.5% and 2.5% of local isolates were type I and type II FCoV, respectively. These isolates had high sequence homology and phylogenetic similarity with several FCoV isolates from Europe, South East Asia and USA. CONCLUSIONS: This study reported the successful isolation of local type I and type II FCoV evident with formation of cytopathic effects in two types of cell cultures namely the CrFK and Fcwf-4 , where the later cells being more permissive. However, the RT-PCR assay is more sensitive in detecting the antigen in suspected samples as compared to virus isolation in cell culture. The present study indicated that type I FCoV is more prevalent among cats in Malaysia.


title: Clinical recommendations on lung cancer management during the COVID‐19 pandemic

text: Coronavirus disease 2019 (COVID‐19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID‐19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID‐19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID‐19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID‐19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID‐19. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides suggestions for early identification of COVID‐19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. WHAT THIS STUDY ADDS: This article makes clinical recommendations on lung cancer management during the COVID‐19 pandemic.


Severe acute respiratory syndrome and the liver


title: A LAD-based method for selecting short oligo probes for genotyping applications

text: Specializing a general framework of logical analysis of data for efficiently handling large-scale genomic data, we develop in this paper a probe design method for selecting short oligo probes for genotyping applications. When tested on genomic sequences obtained from the National Center of Biotechnology Information in various monospecific and polyspecific in silico experiments, the proposed probe design method was able to select a small number of oligo probes of length 7 or 8 nucleotides that perfectly classified all unseen testing sequences. These results demonstrate the efficacy of the proposed probe design method and illustrate the usefulness and potential a well-designed optimization-based probe selection method has in genotyping applications.


title: Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

text: Human herpesviruses are among the most prevalent pathogens worldwide and have become an important public health issue. Recurrent infections and the emergence of resistant viral strains reinforce the need of searching new drugs to treat herpes virus infections. Cardiac glycosides are used clinically to treat cardiovascular disturbances, such as congestive heart failure and atrial arrhythmias. In recent years, they have sparked new interest in their potential anti-herpes action. It has been previously reported by our research group that two new semisynthetic cardenolides, namely C10 (3β-[(N-(2-hydroxyethyl)aminoacetyl]amino-3-deoxydigitoxigenin) and C11 (3β-(hydroxyacetyl)amino-3-deoxydigitoxigenin), exhibited potential anti-HSV-1 and anti-HSV-2 with selectivity index values > 1,000, comparable with those of acyclovir. This work reports the mechanism investigation of anti-herpes action of these derivatives. The results demonstrated that C10 and C11 interfere with the intermediate and final steps of HSV replication, but not with the early stages, since they completely abolished the expression of the UL42 (β) and gD (γ) proteins and partially reduced that of ICP27 (α). Additionally, they were not virucidal and had no prophylactic effects. Both compounds inhibited HSV replication at nanomolar concentrations, but cardenolide C10 was more active than C11 and can be considered as an anti-herpes drug candidate including against acyclovir-resistant HSV-1 strains.


title: COVID‐19 epidemic: Skin protection for health care workers must not be ignored

text: Since first reported in 2019, pneumonia associated with 2019 novel coronavirus disease (COVID‐19) has rapidly developed into an outbreak across the world.(1) Number of the patients of all age groups has increased significantly.(2) In order to curb the spread of the epidemic, thousands of health care workers (HCWs) have joined the front line of the fight against this highly contagious disease.(3) When taking care of patients with COVID‐19 pneumonia, HCWs must first protect themselves by performing adequate hand hygiene and using protective equipment including medical mask, goggles/face shield, gown and gloves.(4) However, the wearing of these personal protective equipment (PPE) on a daily basis and the frequent use of hand disinfectants often cause skin problems which could reduce their enthusiasm for overloaded work and make them anxious at all stages of the pandemic.


When preserving life becomes imperative, quality of life is eclipsed! COVID‐19 outbreak impacting patients with pelvic floor disorders undergoing pelvic floor rehabilitation


Measuring Grip Strength in COVID-19: A Simple Way to Predict Overall Frailty/Impairment


title: Experimental investigation of integrated air purifying technology for bioaerosol removal and inactivation in central air-conditioning system

text: In this research, high voltage static electricity and ultraviolet technologies were integrated to an air purifying device which can be used to trap and kill airborne bacteria and viruses in central air-conditioning systems. An experimental platform was built to mimic the central air system, in which the efficacy of the newly built device was examined. In addition to the standard physical and chemical tests, bacteriophages were used to simulate airborne viruses in the experimental system. The bacteriophage suspension was aerosolized into the air with ultrasonic wave atomization. The result showed that more than 86% removal efficiency of micro-particles (<10 micron in diameter) were removed after the device was in operation in a building and more than 95% of bacteriophages in the experimental system. It is concluded that the integrated air purifier is suitable for controlling air quality and preventing virus transmission through the central air system.


title: An Outlook on the Global Development of Renewable and Sustainable Energy at the Time of Covid-19

text: The outbreak of the novel COVID-19 has dominated the world stage, and its consequences, both direct and indirect, are expected to prove to be even more pervasive over time. The COVID-19 pandemic has struck the renewable energy manufacturing facilities, supply chains, and companies and slowed down the transition to the sustainable energy world. The global decline in economy-driven demand could damage the positive trend of green and low-carbon energy progress. Although it is too early to judge how profound the negative effects of the pandemic on the global renewable and sustainable energy systems will be, a significant short-run contraction to the development of renewables is inevitable. Therefore, the energy and climate policies may require to be restructured based on the new circumstances. In this context, several beneficial stimuluses should be offered by the governments to persuade the private sectors and society to invest on renewables. Undoubtedly, intelligent policies could convert the menaces of COVID-19 to the great opportunities for renewables and ultimately the world’s sustainable energy scenario could return to its long-term trajectory toward green power generation and utilization over the next few years.


Effects of 5‐alpha reductase inhibitors on lung function: A reason for discontinuation during COVID‐19 pandemic?


title: Potential transmission of SARS-CoV-2 on a flight from Singapore to Hanghzou, China: An epidemiological investigation

text: BACKGROUND: Between January 24, 2020 and February 15, 2020, an outbreak of COVID-19 occurred among 335 passengers on a flight from Singapore to Hangzhou in China. This study aimed to investigate the source of the outbreak and assess the risk of transmission of COVID-19 during the flight. METHOD: Using a standardized questionnaire, we collected information on the travelers’ demographic characteristics and illness before, during, and after the flight. We also collected data on factors potentially associated with COVID-19 transmission during the flight. RESULTS: A total of 16 COVID-19 patients were diagnosed among all passengers; the overall attack rate was 4.8%. The attack rate among passengers who had departed from Wuhan was significantly higher than that among those who had departed from other places. One passenger without an epidemiological history of exposure before boarding developed COVID-19. During the flight, he was seated near four infected passengers from Wuhan for approximately an hour and did not wear his facemask correctly during the flight. CONCLUSIONS: COVID-19 transmission may have occurred during the flight. However, the majority of the cases in the flight-associated outbreak could not be attributed to transmission on the flight but were associated with exposure to the virus in Wuhan or to infected members in a single tour group.


title: COVID‐19: A review of therapeutics under investigation

text: The COVID‐19 outbreak has disrupted global health care networks and caused thousands of deaths and an international economic downturn. Multiple drugs are being used on patients with COVID‐19 based on theoretical and in vitro therapeutic targets. Several of these therapies have been studied, but many have limited evidence behind their use, and clinical trials to evaluate their efficacy are either ongoing or have not yet begun. This review summarizes the existing evidence for medications currently under investigation for treatment of COVID‐19, including remdesivir, chloroquine/hydroxychlorquine, convalescent plasma, lopinavir/ritonavir, IL‐6 inhibitors, corticosteroids, and angiotensin‐converting enzyme inhibitors.


title: Advancing a multivalent ‘Pan-anthelmintic’ vaccine against soil-transmitted nematode infections

text: ASCARIS LUMBRICOIDES: The Sabin Vaccine Institute Product Development Partnership is developing a Pan-anthelmintic vaccine that simultaneously targets the major soil-transmitted nematode infections, in other words, ascariasis, trichuriasis and hookworm infection. The approach builds off the current bivalent Human Hookworm Vaccine now in clinical development and would ultimately add both a larval Ascaris lumbricoides antigen and an adult-stage Trichuris trichiura antigen from the parasite stichosome. Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively. Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions. Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.


title: Pathogen-Tested Planting Material

text: Abstract Certification programs have been developed to provide plant material that meets a predetermined level of plant health. The primary objectives of these programs are to limit pathogen incidence in plant material in order to minimize losses by growers and prevent movement of harmful pests and pathogens that may harm the environment. For many fruit and nut crops, orchards are expected to remain productive for years or decades; thus, starting with plants of high health status is essential. The components of certification programs in terms of plant health will be outlined, along with the benefits of harmonizing these programs where possible to facilitate plant movement without increasing trade in plant pathogens.


title: Potential Impact of Antiviral Drug Use during Influenza Pandemic

text: The recent spread of highly pathogenic strains of avian influenza has highlighted the threat posed by pandemic influenza. In the early phases of a pandemic, the only treatment available would be neuraminidase inhibitors, which many countries are considering stockpiling for pandemic use. We estimate the effect on hospitalization rates of using different antiviral stockpile sizes to treat infection. We estimate that stockpiles that cover 20%–25% of the population would be sufficient to treat most of the clinical cases and could lead to 50% to 77% reductions in hospitalizations. Substantial reductions in hospitalization could be achieved with smaller antiviral stockpiles if drugs are reserved for persons at high risk.


Regarding COVID‐19 and the Otolaryngologist: Preliminary Evidence‐Based Review


title: In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2

text: In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 μM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.


title: Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

text: Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.


title: Development of Small-Molecule MERS-CoV Inhibitors

text: Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection.


Convalescent plasma for COVID-19 in pregnancy: a case report and review


title: COVID-19: Lessons for the climate change emergency

text: The ongoing COVID-19 outbreak pandemic is now a global crisis. It has caused 9+ million confirmed cases and 400,000+ deaths at the time of writing and triggered unprecedented preventative measures that have confined a substantial portion of the global population and established ‘social distancing’ as a new global behavioral norm. The COVID-19 crisis has affected all aspects of everyday life and work, and heavily impacted the global economy. This crisis also offers unprecedented insights into how the global climate crisis may be managed, as there are many parallels between the COVID-19 crisis and what we expect from the imminent global climate emergency. Reflecting upon the challenges of today's crisis may help us better prepare for the future. Here we compile a list, by no means comprehensive, of the similarities and differences between the two crises, and the lessons we can learn from them: (i) High momentum trends, (ii) Irreversible changes, (iii) Social and spatial inequality, (iv) Weakening of international solidarity, and (v) Less costly to prevent than to cure.


title: Detection of HIV-1 RNA/DNA and CD4 mRNA in feces and urine from chronic HIV-1 infected subjects with and without anti-retroviral therapy

text: HIV-1 infects gut associated lymphoid tissues (GALT) very early after transmission by multiple routes. The infected GALT consequently serves as the major reservoir for HIV-1 infection and could constantly shed HIV-1 and CD4(+ )T cells into the intestinal lumen. To examine this hypothesis, we monitored HIV-1 RNA/DNA and CD4 mRNA in fecal samples of chronically infected subjects with and without antiretroviral therapy (ART). We compared this to levels of HIV-1 RNA/DNA in urine and blood from the same subjects. Our results show that HIV-1 DNA, RNA and CD4 mRNA were detected in 8%, 19% and 31% respectively, of feces samples from infected subjects with detectable plasma viral load, and were not detected in any of subjects on ART with undetectable plasma viral load. In urine samples, HIV-1 DNA was detected in 24% of infected subjects with detectable plasma viral load and 23% of subjects on ART with undetectable plasma viral load. Phylogenetic analysis of the envelope sequences of HIV-1 revealed distinct virus populations in concurrently collected serum, feces and urine samples from one subject. In addition, our study demonstrated for the first time the presence of CD4 mRNA in fecal specimens of HIV-1 infected subjects, which could be used to assess GALT pathogenesis in HIV-1 infection.


title: COVID-19 and Acute Pancreatitis: What Do Surgeons Need to Know?

text: Coronavirus disease 2019 (COVID-19) typically presents with pulmonary symptoms. Extra-pulmonary symptomatology of COVID-19 has drawn significant attention. However, information about the incidence, course and outcomes of acute pancreatitis in these patients is still limited.


title: Identification by functional proteomics of a deubiquitinating/deNeddylating enzyme in Plasmodium falciparum

text: Ubiquitination is a post‐translational modification implicated in a variety of cellular functions, including transcriptional regulation, protein degradation and membrane protein trafficking. Ubiquitin and the enzymes that act on it, although conserved and essential in eukaryotes, have not been well studied in parasites, despite sequencing of several parasite genomes. Several putative ubiquitin hydrolases have been identified in Plasmodium falciparum based on sequence homology alone, with no evidence of expression or function. Here we identify the first deubiquitinating enzyme in P. falciparum, PfUCH54, by its activity. We show that PfUCH54 also has deNeddylating activity, as assayed by a mammalian Nedd8‐based probe. This activity is absent from mammalian homologues of PfUCH54. Given the importance of parasitic membrane protein trafficking as well as protein degradation in the virulence of this parasite, this family of enzymes may represent a target for pharmacological intervention with this disease.


ASE Statement on the Reintroduction of Echocardiography Services During the COVID-19 Pandemic


title: Hospital Emergency Management Plan During the COVID‐19 Epidemic

text: The confirmed and suspected cases of the 2019 novel coronavirus disease (COVID-19) have increased not only in Wuhan, Hubei Province but also China and the world. Enormous demand for handling the COVID-19 outbreak challenged both the healthcare personnel and medical supply system. In West China Hospital, Emergency Department (ED) undertook the mission of clinical reception, primary diagnosis, and interim treatment for the suspected cases of COVID-19.


title: Air Pollution and temperature are associated with increased COVID-19 incidence: a time series study

text: OBJECTIVES: Although the COVID-19 is known to cause by human-to-human transmission, it remains largely unclear whether ambient air pollutants and meteorological parameters could promote its transmission. METHODS: A retrospective study is conducted to study whether air quality index (AQI), four ambient air pollutants (PM(2.5), PM(10), NO(2) and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase COVID-19 incidence in Wuhan and XiaoGan between Jan 26(th) to Feb 29(th) in 2020. RESULTS: First, a significant correlation was found between COVID-19 incidence and AQI in both Wuhan (R(2) = 0.13, p < 0.05) and XiaoGan (R(2) = 0.223, p < 0.01). Specifically, among four pollutants, COVID-19 incidence was prominently correlated with PM(2.5) and NO(2) in both cities. In Wuhan, the tightest correlation was observed between NO(2) and COVID-19 incidence (R(2) = 0.329, p < 0.01). In XiaoGan, in addition to the PM(2.5) (R(2) = 0.117, p < 0.01) and NO(2) (R(2) = 0.015, p < 0.05), a notable correlation was also observed between the PM(10) and COVID-19 incidence (R(2) = 0.105, p < 0.05). Moreover, temperature is the only meteorological parameter that constantly correlated well with COVID-19 incidence in both Wuhan and XiaoGan, but in an inverse correlation (p < 0.05). CONCLUSIONS: AQI, PM(2.5), NO(2), and temperature are four variables that could promote the sustained transmission of COVID-19.


title: Bioaerosols and Transmission, a Diverse and Growing Community of Practice

text: The transmission of infectious microbes via bioaerosols is of significant concern for both human and animal health. However, gaps in our understanding of respiratory pathogen transmission and methodological heterogeneity persist. New developments have enabled progress in this domain, and one of the major turning points has been the recognition that cross-disciplinary collaborations across spheres of human and animal health, microbiology, biophysics, engineering, aerobiology, infection control, public health, occupational health, and industrial hygiene are essential. Collaborative initiatives support advances in topics such as bioaerosol behavior, dispersion models, risk assessment, risk/exposure effects, and mitigation strategies in clinical, experimental, agricultural, and other field settings. There is a need to enhance the knowledge translation for researchers, stakeholders, and private partners to support a growing network of individuals and agencies to achieve common goals to mitigate inter- and intra-species pathogen transmission via bioaerosols.


title: Rhabdomyolysis in a Patient With Coronavirus Disease 2019

text: Coronavirus disease 2019 has rapidly enveloped the world in a pandemic after emerging in Wuhan, China, in December 2019. We describe a 49-year-old man presenting with fever, cough, dyspnea, and myalgia diagnosed with coronavirus disease 2019 along with rhabdomyolysis and acute kidney injury. The creatine phosphokinase was elevated to 23,800 U/L before trending down to normal levels. Rapid identification and treatment with aggressive intravenous hydration and correction of electrolyte abnormalities remain key to successful management. In a pandemic, often atypical presentations of this new disease have to be considered as differentials for early diagnosis and treatment of life-threatening conditions.


Obstructive Sleep Apnea, Obesity, and Noninvasive Ventilation: Considerations During the Coronavirus Disease 2019 Pandemic


title: A clinical approach to the threat of emerging influenza viruses in the Asia‐Pacific region

text: Seasonal influenza epidemics and periodic pandemics are important causes of morbidity and mortality. Patients with chronic co‐morbid illness, those at the extremes of age and pregnant women are at higher risks of complications requiring hospitalization, whereas young adults and obese individuals were also at increased risk during the A(H1N1) pandemic in 2009. Avian influenza A(H5N1) and A(H7N9) viruses have continued to circulate widely in some poultry populations and infect humans sporadically since 1997 and 2013, respectively. The recent upsurge in human cases of A(H7N9) infections in Mainland China is of great concern. Sporadic human cases of avian A(H5N6), A(H10N8) and A(H6N1) have also emerged in recent years while there are also widespread poultry outbreaks due to A(H5N8) in many countries. Observational studies have shown that treatment with a neuraminidase inhibitor (NAI) for adults hospitalized with severe influenza is associated with lower mortality and better clinical outcomes, especially when administered early in the course of illness. Whether higher than standard doses of NAI would provide greater antiviral effects in such patients will require further investigation. High‐dose systemic corticosteroids were associated with worse outcomes in patients with severe influenza. There is an urgent need for developing more effective antiviral therapies for treatment of influenza infections.


title: Structural parameterization and functional prediction of antigenic polypeptome sequences with biological activity through quantitative sequence-activity models (QSAM) by molecular electronegativity edge-distance vector (VMED)

text: Only from the primary structures of peptides, a new set of descriptors called the molecular electronegativity edge-distance vector (VMED) was proposed and applied to describing and characterizing the molecular structures of oligopeptides and polypeptides, based on the electronegativity of each atom or electronic charge index (ECI) of atomic clusters and the bonding distance between atom-pairs. Here, the molecular structures of antigenic polypeptides were well expressed in order to propose the automated technique for the computerized identification of helper T lymphocyte (Th) epitopes. Furthermore, a modified MED vector was proposed from the primary structures of polypeptides, based on the ECI and the relative bonding distance of the fundamental skeleton groups. The side-chains of each amino acid were here treated as a pseudo-atom. The developed VMED was easy to calculate and able to work. Some quantitative model was established for 28 immunogenic or antigenic polypeptides (AGPP) with 14 (1–14) A(d) and 14 other restricted activities assigned as “1”(+) and “0”(−), respectively. The latter comprised 6 A(b)(15–20), 3 A(k)(21–23), 2 E(k)(24–26), 2 H-2(k)(27 and 28) restricted sequences. Good results were obtained with 90% correct classification (only 2 wrong ones for 20 training samples) and 100% correct prediction (none wrong for 8 testing samples); while contrastively 100% correct classification (none wrong for 20 training samples) and 88% correct classification (1 wrong for 8 testing samples). Both stochastic samplings and cross validations were performed to demonstrate good performance. The described method may also be suitable for estimation and prediction of classes I and II for major histocompatibility antigen (MHC) epitope of human. It will be useful in immune identification and recognition of proteins and genes and in the design and development of subunit vaccines. Several quantitative structure activity relationship (QSAR) models were developed for various oligopeptides and polypeptides including 58 dipeptides and 31 pentapeptides with angiotensin converting enzyme (ACE) inhibition by multiple linear regression (MLR) method. In order to explain the ability to characterize molecular structure of polypeptides, a molecular modeling investigation on QSAR was performed for functional prediction of polypeptide sequences with antigenic activity and heptapeptide sequences with tachykinin activity through quantitative sequence-activity models (QSAMs) by the molecular electronegativity edge-distance vector (VMED). The results showed that VMED exhibited both excellent structural selectivity and good activity prediction. Moreover, the results showed that VMED behaved quite well for both QSAR and QSAM of poly-and oligopeptides, which exhibited both good estimation ability and prediction power, equal to or better than those reported in the previous references. Finally, a preliminary conclusion was drwan: both classical and modified MED vectors were very useful structural descriptors. Some suggestions were proposed for further studies on QSAR/QSAM of proteins in various fields.


title: Telecommuting: A viable option for medical physicists amid the COVID‐19 outbreak and beyond

text: The impact of recent outbreak of novel coronavirus disease, COVID-19, to the global healthcare systems is unprecedently enormous. Like many other clinical disciplines, medical physics has encountered unique challenges during this special period in wider aspects from clinical practice, research, administration to education. As hospitals implement various preventive and control measures to contain the virus, medical physicists are asked to perform non-essential activities by telecommuting or work-from-home (WFH) in many places.


title: Human adenovirus load in respiratory tract secretions are predictors for disease severity in children with human adenovirus pneumonia

text: BACKGROUND: Pneumonia is a serious public health issue and is concerned around the world. This study is to investigate the association between viral load in children with human adenovirus (HAdV) pneumonia and disease severity. METHODS: A total of 1313 cases of children hospitalized in Hunan Provincial People’s Hospital due to community acquired pneumonia (CAP) from April 2011 to May 2014 were enrolled in this study. Samples of nasopharyngeal aspirate were collected for the cohort. WHO criteria for CAP grading was emerged for pneumonia severity classification. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect 12 kinds of respiratory viruses. HAdV types were identified by nested PCR. The relationship between HAdV load and severity of disease was there by analyzed. RESULTS: Finally, 174 cases (174/1313, 13.3%) were positive for HAdV, and HAdV type 7 (HAdV-7) was the main serotype (76/174, 43.7%). Among the 174 cases, 70 cases were with HAdV infection alone and 104 cases were accompanied by other viruses. The patients were divided into mild pneumonia group (n = 108 cases) and severe pneumonia group (n = 66 cases). HAdV load of children in severe pneumonia group was higher than that in mild pneumonia group. Similar result was obtained in the 70 cases with HAdV infection alone after subgrouping. Relevant factors analysis results showed that severe pneumonia children presented lower onset age, more prone to fever, longer fever time, and longer hospital stay compared with that of mild pneumonia children. Children with HAdV-7 infection developed more frequently severe pneumonia. Multivariate regression analysis showed that HAdV load, age, and fever time were risk factors for pneumonia severity. CONCLUSION: The severity of HAdV infection is significantly correlated with viral load and serotype.


title: Nasal virome of dogs with respiratory infection signs include novel taupapillomaviruses

text: Using viral metagenomics, we characterized the mammalian virome of nasal swabs from 57 dogs with unexplained signs of respiratory infection showing mostly negative results using the IDEXX Canine Respiratory Disease RealPCR™ Panel. We identified canine parainfluenza virus 5, canine respiratory coronavirus, carnivore bocaparvovirus 3, canine circovirus and canine papillomavirus 9. Novel canine taupapillomaviruses (CPV21-23) were also identified in 3 dogs and their complete genome sequenced showing L1 nucleotide identity ranging from 68.4 to 70.3% to their closest taupapillomavirus relative. Taupapillomavirus were the only mammalian viral nucleic acids detected in two affected dogs, while a third dog was coinfected with low levels of canine parainfluenza 5. A role for these taupapillomavirues in canine respiratory disease remains to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-019-01634-6) contains supplementary material, which is available to authorized users.


title: Response to Emergence of Middle East Respiratory Syndrome Coronavirus, Abu Dhabi, United Arab Emirates, 2013–2014

text: In January 2013, several months after Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia, Abu Dhabi, United Arab Emirates, began surveillance for MERS-CoV. We analyzed medical chart and laboratory data collected by the Health Authority–Abu Dhabi during January 2013–May 2014. Using real-time reverse transcription PCR, we tested respiratory tract samples for MERS-CoV and identified 65 case-patients. Of these patients, 23 (35%) were asymptomatic at the time of testing, and 4 (6%) showed positive test results for >3 weeks (1 had severe symptoms and 3 had mild symptoms). We also identified 6 clusters of MERS-CoV cases. This report highlights the potential for virus shedding by mildly ill and asymptomatic case-patients. These findings will be useful for MERS-CoV management and infection prevention strategies.


title: Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2

text: Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric VSV containing the envelope proteins of Zaire ebolavirus (VSV-ZEBOV) or SARS-CoV-2 (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small molecule inhibitors of the main endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase, PIKfyve. We also describe potent inhibition of SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020 by Apilimod. These results define new tools for studying the intracellular trafficking of pathogens elicited by inhibition of PIKfyve kinase and suggest the potential for targeting this kinase in developing small-molecule antivirals against SARS-CoV-2.


title: Autoimmune and inflammatory diseases following COVID-19

text: Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae.


title: Current knowledge, attitude and behaviour of hand and food hygiene in a developed residential community of Singapore: a cross-sectional survey

text: BACKGROUND: Diarrhoea incidence has been increasing progressively over the past years in developed countries, including Singapore, despite the accessibility and availability to clean water, well-established sanitation infrastructures and regular hygiene promotion. The aim of this study is to determine the current knowledge, attitude and behaviour of hand and food hygiene, and the potential risk factors of diarrhoea in a residential community of Singapore. METHODS: A cross-sectional study was conducted within a residential area in the west of Singapore from June to August 2013. A total of 1,156 household units were randomly sampled and invited to participate in an interviewer-assisted survey using standardised questionnaires. Descriptive, univariate and multivariate analyses were performed using descriptive statistics, Fisher’s Exact test and multivariate logistic regression modelling, respectively. R program was used for all statistical analysis. All tests were conducted at 5 % level of significance with 95 % confidence intervals (CI) reported where applicable. RESULTS: A total of 240 units (20.8 %) consented and responded to the survey invitation. About 77 % of the expected knowledge and attitude were observed in at least 80 % of the participants, compared to only about 31 % of the expected behaviours and practises. Being single [adjusted odds ratio (AOR) = 2.29; 95 % CI = 1.16-4.48], having flu in the past six month (AOR = 3.24; 95 % CI = 1.74-6.06), preferred self-medication (AOR = 2.07; 95 % CI = 1.06–4.12) were risk factors of diarrhoea. Washing hands with water before attending to children or sick persons (AOR = 0.30; 95 % CI = 0.11–0.82), washing hands with water (AOR = 0.16; 95 % CI = 0.05–0.45) and water with soap (AOR = 0.29; 95 % CI = 0.12–0.72) after attending to children or sick persons, and hand washing between 30 s to a minute (AOR = 0.44; 95 % CI = 0.20-0.90) were protective factors against diarrhoea. CONCLUSIONS: Good knowledge and attitude of the participants did not positively translate into high compliance and motivation to perform good hygiene practices. This observation may have resulted in a significant extent on the increasing diarrhoea incidences. Current interventions may be improved with more active community partnership among the residents, schools and the relevant social organizations, to raise awareness on the importance of compliance to good hygiene practices, and the risk factors of diarrhoea. A large case–control study would be required to validate these findings in future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1910-3) contains supplementary material, which is available to authorized users.


title: MMPs and ADAMs in neurological infectious diseases and multiple sclerosis

text: Metalloproteinases—such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs)—are involved in various diseases of the nervous system but also contribute to nervous system development, synaptic plasticity and neuroregeneration upon injury. MMPs and ADAMs proteolytically cleave many substrates including extracellular matrix components but also signaling molecules and receptors. During neuroinfectious disease with associated neuroinflammation, MMPs and ADAMs regulate blood–brain barrier breakdown, bacterial invasion, neutrophil infiltration and cytokine signaling. Specific and broad-spectrum inhibitors for MMPs and ADAMs have experimentally been shown to decrease neuroinflammation and brain damage in diseases with excessive neuroinflammation as a common denominator, such as pneumococcal meningitis and multiple sclerosis, thereby improving the disease outcome. Timing of metalloproteinase inhibition appears to be critical to effectively target the cascade of pathophysiological processes leading to brain damage without inhibiting the neuroregenerative effects of metalloproteinases. As the critical role of metalloproteinases in neuronal repair mechanisms and regeneration was only lately recognized, the original idea of chronic MMP inhibition needs to be conceptually revised. Recently accumulated research urges for a second chance of metalloproteinase inhibitors, which—when correctly applied and dosed—harbor the potential to improve the outcome of different neuroinflammatory diseases.


title: Rôle des infections rhino-sinusiennes dans le déclenchement des pathologies allergiques et inflammatoires

text: Summary Much controversy still exists about the role of viruses, bacteria and fungi in nasal sinus diseases. Viral rhinitis alone does not seem to be able to elicit clinical acute sinusitis. Bacteria determine the clinical picture and outcome of sinusitis. S. pneumoniae, H. influenzae and M. catarrhalis are the bacteria most frequently involved. Much more conflicting reports are published about normal sinus flora, the role of anaerobes and the microbiology of chronic sinusitis. The relationship between infectious and allergic diseases ise more difficult to explain. It is shown that, in particular viruses can induce the release of inflammatory mediators and modify the inflammatory process. Their role in epithelial damage, excitation of nerve fibers, sensitization of inflammatory cells, and therefore, in general hyperreactivity has also been reported. Finally, with regard to sinusitis, different hypothesis have been proposed to explain the possible links with bronchial hyperreactivity.


Life at the Editorial “COVID Frontline”. The American Thoracic Society Journal Family


title: Gastrointestinal and Liver Manifestations of COVID-19

text: The worldwide pandemic of COVID-19, caused by the virus SARS-CoV,-2 has continued to progress, and increasing information is becoming available about the incidence of digestive symptoms as well as abnormal liver-associated enzymes in patients who are infected. These are postulated to be related to the virus's use of ACE-2 receptors located on certain intestinal cells, cholangiocytes, and hepatocytes. This brief review summarizes the available limited data on digestive manifestations of COVID-19. A significant proportion of COVID-19 patients can present initially with only digestive complaints. The most common digestive symptoms are anorexia, nausea, vomiting, and diarrhea. Liver-related transaminases are elevated in a substantial proportion of patients, although generally only mildly elevated. Currently there is no firm evidence to suggest that severity of digestive symptoms corresponds to severity of COVID-19 clinical course, however, more severe alterations in liver enzymes may correlate with worse clinical course. Given use of antiviral and antibacterial agents in sicker patients, drug-induced liver injury cannot be ruled out either in these cases. Although viral RNA can be detected in stool, it is unclear whether fecal-oral transmission can be achieved by the virus. As further data becomes available, our understanding of the digestive manifestations of COVID-19 will continue to evolve.


title: Evaluating a multicomponent program to improve hypertension control in Guatemala: study protocol for an effectiveness-implementation cluster randomized trial

text: BACKGROUND: Hypertension is a major risk factor for cardiovascular disease (CVD). Despite advances in hypertension prevention and treatment, the proportion of patients who are aware, treated and controlled is low, particularly in low-income and middle-income countries (LMICs). We will evaluate an adapted version of a multilevel and multicomponent hypertension control program in Guatemala, previously proven effective and feasible in Argentina. The program components are: protocol-based hypertension treatment using a standardized algorithm; team-based collaborative care; health provider education; health coaching sessions; home blood pressure monitoring; blood pressure audit; and feedback. METHODS: Using a hybrid type 2 effectiveness-implementation design, we will evaluate clinical and implementation outcomes of the multicomponent program in Guatemala over an 18-month period. Through a cluster randomized trial, we will randomly assign 18 health districts to the intervention arm and 18 to enhanced usual care across five departments, enrolling 44 participants per health district and 1584 participants in total. The clinical outcomes are (1) the difference in the proportion of patients with controlled hypertension (< 130/80 mmHg) between the intervention and control groups at 18 months and (2) the net change in systolic and diastolic blood pressure from baseline to 18 months. The context-enhanced Reach, Efficacy, Adoption, Implementation, Maintenance (RE-AIM)/Practical Robust Implementation and Sustainability Model (PRISM) framework will guide the evaluation of the implementation at the level of the patient, provider, and health system. Using a mixed-methods approach, we will evaluate the following implementation outcomes: acceptability, adoption, feasibility, fidelity, adaptation, reach, sustainability, and cost-effectiveness. DISCUSSION: We will disseminate the study findings, and promote scale up and scale out of the program, if proven effective. This study will generate urgently needed data on effective, adoptable, and sustainable interventions and implementation strategies to improve hypertension control in Guatemala and other LMICs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03504124. Registered on 20 April 2018.


title: Isolation of a thermostable trypsin inhibitor with exploitable potential

text: A novel trypsin inhibitor with considerable thermal and pH stability, designated Glytine, was isolated from seeds of the Chinese black soybean Glycine max (L.) Merr. The purification procedure involved ammonium sulfate precipitation, ion-exchange chromatography on CM-Sephadex C-50, gel filtration chromatography on Sephacryl S-200HR, and gel filtration chromatography on POROS HS-20. The 20 N-terminal amino acid sequences were determined to be DEYSKPCCDLCMCTRRCPPQ, demonstrating close homology with the sequences of leguminous trypsin inhibitors. The molecular mass and isoelectric point of the inhibitor were estimated by SDS-PAGE and isoelectric focusing to be 19.9 kDa and 6.2, respectively. Trypsin could be completely inhibited by Glytine when the weight ratio was 1.5. The inhibitory activity of Glytine was unaffected by exposure to temperatures up to 100 °C, or within the pH range 2–12. Besides trypsin–chymotrypsin inhibition activity, Glytine demonstrated other biological activities including antiproliferative activity against tumor cells including human liver hepatoma cells Bel-7402 and neuroblastoma cells SHSY5Y. In addition, the inhibitor showed antifungal activity against Pythium aphanidermatum, Fusarium oxysporum, Alternaria alternata (Fr.) Keiss, Fusarium solani, and Botrytis cinerea. This study extended research on leguminous trypsin–chymotrypsin inhibitor and suggested exploitable potential.


title: Hepatitis E Virus ORF2 Protein Activates the Pro-Apoptotic Gene CHOP and Anti-Apoptotic Heat Shock Proteins

text: BACKGROUND: Hepatitis E virus (HEV) is a non-enveloped plus-strand RNA virus that causes acute hepatitis. The capsid protein open reading frame 2 (ORF2) is known to induce endoplasmic reticulum stress in ORF2 expressing cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study we found that HEV ORF2 activates the expression of the pro-apoptotic gene C/EBP homologous protein (CHOP). ORF2 stimulates the CHOP promoter mainly through AARE (amino acid response elements) and to a minor extent the ERSE (endoplasmic reticulum stress response elements). Activating transcription factor 4 (ATF4) protein binds and activates the AARE regulatory sites of the CHOP promoter. ORF2 expression also leads to increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) that in turn initiates the translation of ATF4 mRNA. The pro-apoptotic gene CHOP is an important trigger to initiate endoplasmic reticulum stress induced apoptosis. However, the activation of CHOP by ORF2 in this study did not induce apoptosis, nor did BCL2-associated X protein (Bax) translocate to mitochondria. Microarray analysis revealed an ORF2 specific increased expression of chaperones Hsp72, Hsp70B', and co-chaperone Hsp40. Co-immunoprecipitation (Co-IP) and in silico molecular docking analysis suggests that HEV ORF2 interacts with Hsp72. In addition, Hsp72 shows nuclear accumulation in ORF2 expressing cells. CONCLUSIONS/SIGNIFICANCE: These data provide new insight into simultaneously occurring counter-acting effects of HEV ORF2 that may be part of a strategy to prevent host suicide before completion of the viral replication cycle.


title: Titration of Human Coronaviruses, HCoV-229E and HCoV-OC43, by an Indirect Immunoperoxidase Assay

text: Calculation of infectious viral titers represents a basic and essential experimental approach for virologists. Classical plaque assays cannot be used for viruses that do not cause significant cytopathic effects, which is the case for strains 229E and OC43 of human coronavirus (HCoV). An alternative indirect immunoperoxidase assay (IPA) is herein described for the detection and titration of these viruses. Susceptible cells are inoculated with serial logarithmic dilutions of samples in a 96-well plate. After viral growth, viral detection by IPA yields the infectious virus titer, expressed as “tissue culture infectious dose” (TCID(50)). This represents the dilution of a virus-containing sample at which half of a series of laboratory wells contain replicating virus. This technique is a reliable method for the titration of HCoV in biological samples (cells, tissues, or fluids).


title: The spike protein of SARS-CoV — a target for vaccine and therapeutic development

text: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.


Scaling up testing for COVID-19 in Africa: Responding to the pandemic in ways that strengthen health systems


title: Tobacco use and vaping in the COVID‐19 era

text: Health crises have become a popular topic of discussion. In the wave of the ongoing pandemic, experts have suggested the role of vaping and other tobacco product use exemplifying the vulnerability of the population to contract the COVID‐19. We discuss some of the events that led up to these conclusions and also offer a unique insight into another form of tobacco use that is potentially propagating its spread especially in the South Asian region—chewed tobacco. Both of these have been a perennial issue that head and neck cancer surgeons have been dealing with. Governments and head and neck cancer care providers now have an opportunity to deal with a common enemy in the midst of this pandemic.


title: COVID-19, insurer board utility, and capital regulation

text: This paper develops a down-and-out call option model by introducing a structural break in volatility to capture the coronavirus (COVID-19) outbreak. The life insurer's equity and its board's utility are evaluated at the optimal guaranteed rate in the equity maximization. Results suggest that the seriousness degree of the COVID-19 outbreak and capital regulation enhance the optimal guaranteed rate and the board's utility. Increased the board's utility by increasing liabilities costs insurer profitability. Conflicts of incentives can arise during the COVID-19 outbreak.


COVID-19 and the Ophthalmology Match


title: Impacto de la pandemia COVID-19 en el servicio de urología de un centro de referencia en la Comunidad de Madrid

text: Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has caused tens of thousands of deaths in Spain and has managed to breakdown the healthcare system hospitals in the Community of Madrid, largely due to its tendency to cause severe pneumonia, requiring ventilatory support. This fact has caused our center to collapse, with 130% of its beds occupied by COVID-19 patients, thus causing the absolute cessation of activity of the urology service, the practical disappearance of resident training programs, and the incorporation of a good part of the urology staff into the group of medical personnel attending these patients. In order to recover from this extraordinary level of suspended activity, we will be obliged to prioritize pathologies based on purely clinical criteria, for which tables including the relevance of each pathology within each area of urology are being proposed. Technology tools such as online training courses or surgical simulators may be convenient for the necessary reestablishment of resident education.


title: Etiology and Risk Factors for Mortality in an Adult Community-acquired Pneumonia Cohort in Malawi

text: Rationale: In the context of rapid antiretroviral therapy rollout and an increasing burden of noncommunicable diseases, there are few contemporary data describing the etiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa. Objectives: To describe the current etiology of CAP in Malawi and identify risk factors for mortality. Methods: We conducted a prospective observational study of adults hospitalized with CAP to a teaching hospital in Blantyre, Malawi. Etiology was defined by blood culture, Streptococcus pneumoniae urinary antigen detection, sputum mycobacterial culture and Xpert MTB/RIF, and nasopharyngeal aspirate multiplex PCR. Measurements and Main Results: In 459 patients (285 [62.1%] males; median age, 34.7 [interquartile range, 29.4–41.9] yr), 30-day mortality was 14.6% (64/439) and associated with male sex (adjusted odds ratio, 2.60 [95% confidence interval, 1.17–5.78]), symptom duration greater than 7 days (2.78 [1.40–5.54]), tachycardia (2.99 [1.48–6.06]), hypoxemia (4.40 [2.03–9.51]), and inability to stand (3.59 [1.72–7.50]). HIV was common (355/453; 78.4%), frequently newly diagnosed (124/355; 34.9%), but not associated with mortality. S. pneumoniae (98/458; 21.4%) and Mycobacterium tuberculosis (75/326; 23.0%) were the most frequently identified pathogens. Viral infection occurred in 32.6% (148/454) with influenza (40/454; 8.8%) most common. Bacterial–viral coinfection occurred in 9.1% (28/307). Detection of M. tuberculosis was associated with mortality (adjusted odds ratio, 2.44 [1.19–5.01]). Conclusions: In the antiretroviral therapy era, CAP in Malawi remains predominantly HIV associated, with a large proportion attributable to potentially vaccine-preventable pathogens. Strategies to increase early detection and treatment of tuberculosis and improve supportive care, in particular the correction of hypoxemia, should be evaluated in clinical trials to address CAP-associated mortality.


title: Clinical characteristics and therapeutic procedure for a critical case of novel coronavirus pneumonia treated with glucocorticoids and non-invasive ventilator treatment

text: The novel coronavirus pneumonia (NCP) outbreak occurred in Wuhan, China at the end of 2019. Here, we report the clinical characteristics and therapeutic procedure for a case of severe NCP. The patient was started on glucocorticoids and non-invasive ventilator treatment. After treatment, the patient’s symptoms improved, and the status was confirmed as NCP negative. Our results may provide clues for the treatment of NCP.


title: COVID‐19: From pathogenesis models to the first drug trials

text: The number of people infected with SARS‐CoV‐2, and sadly dying from COVID‐19, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision‐making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini‐review is an update of earlier reports (Brüssow, Microb Biotechnol 2020a;13:607; Brüssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592).


title: Severe maternal morbidity and mortality associated with COVID‐19: The risk should not be down‐played

text: Nordic countries have a long tradition of collecting health related population data meticulously and reporting them transparently. Such data provide firm grounds for making good decisions and as a result the public health institutions in Scandinavia enjoy the trust of society. The Covid‐19 pandemic has, however, resulted in a completely new situation as we are now exploring in uncharted waters. Based on reports from China,(1,2,3) Italy,(4) USA(5) and perhaps with the good intention of reducing anxiety among this vulnerable population group, it has been widely publicized that pregnant women are not at increased risk of susceptibility, infectivity and severity of COVID‐19 compared to the general population or non‐pregnant women, although a systematic review of 108 cases of laboratory confirmed pregnancies with COVID‐19 has reported the possibility of increased risk of severe disease among pregnant women.(6)


title: Association between dopamine and cerebral autoregulation in preterm neonates

text: BACKGROUND: To test the hypothesis that dopamine is associated with impaired cerebral autoregulation (ICA) in a dose-dependent fashion. METHODS: Non a priori designed secondary analysis of a prospectively enrolled cohort study subjects <12 h of life between 24(0) and 29(6) weeks gestation. Cerebral saturations (rScO2) and mean arterial blood pressure (MAP) were continuously monitored every 30 s for 96 h. ICA was defined by a 10 min epoch rScO2-MAP correlation coefficient of >0.5. RESULTS: Twenty-three of 61 subjects (38%) required dopamine. Time spent with ICA was 23% in dopamine-exposed subjects vs. 14% in those not exposed (p = 0.0001). On the epoch level, time spent with ICA was 15%, 29%, 34%, 37%, and 23% in epochs with dopamine titration of 0, 1–5, 6–10, 11–15, and 16–20 μg/kg/min, respectively. Using mixed-effect modeling, ICA for each dopamine titration was significantly higher than unexposed times when controlling for gestation, presence of a patent ductus arteriosus, day of life, MAP less than gestational age, and illness severity score (p < 0.02). CONCLUSIONS: Dopamine exposure during the first 96 h was associated with ICA. Time periods with ICA increased with dopamine exposure in a dose-dependent fashion peaking at a concentration of 11–15 μg/kg/min.


title: Informing Emergency Care for all patients: The Registry for Emergency Care (REC) Project Protocol

text: OBJECTIVES: In Australia, the current emergency department (ED) burden related to COVID‐19 is from ‘suspected’ rather than ‘confirmed’ cases. The initial aim of the Registry for Emergency Care (REC) Project is to determine the impact of isolation processes on the emergency care of all patients. METHODS: The REC Project builds on the COVID‐19 Emergency Department Quality Improvement Project (COVED). Outcomes measured include times to critical assessment and management. RESULTS: Clinical tools will be generated to inform emergency care, both during and beyond the COVID‐19 pandemic. CONCLUSIONS: The REC Project will support ED clinicians in the emergency care of all patients. This article is protected by copyright. All rights reserved.


Lessons learned from HIV can inform our approach to COVID‐19 stigma


title: Outcome of phacoemulsification in 71 cats: A multicenter retrospective study (2006‐2017)

text: PURPOSE: To assess outcome of phacoemulsification in cats. METHODS: Records of 71 cats (82 eyes) from five referral centers were reviewed. Groups were divided by cause of cataract (congenital/juvenile [n = 32], traumatic [n = 33], and secondary to uveitis [n = 6]), and group comparisons were performed for the most common complications: postoperative ocular hypertension (POH), uveitis, corneal ulceration, synechia/dyscoria, and posterior capsular opacity (PCO) in three different time periods: immediately postoperatively, at 1‐90 days, and at >90 days. RESULTS: Median follow‐up was 198 days (interquartile range 64‐518 days). The overall visual success rate of the cats with a 12‐month follow‐up was 92.6% (25/27 eyes). POH occurred in 35/82 (42.6%) eyes. Immediately postoperatively, uveitis was the most common complication in 28/82 eyes (34.1%) followed by corneal ulceration in 22/82 eyes (26.8%). At 1‐90 days, uveitis in 41/81 eyes (50.6%) remained the most common complication, followed by synechia/dyscoria in 21/81 eyes (25.9%), corneal ulceration in 16/81 eyes (19.7%), and PCO in 15/81 eyes (18.5%). At >90 days, PCO in 17/47 eyes (36.1%), followed by synechia/dyscoria in 16/47 eyes (34%), was the most common complications. The number of eyes with synechia/dyscoria in the trauma group was higher (13/33 [39.3%]) than in the congenital/juvenile group (5/31 [16.1%]) at 1‐90 days (P = .039). No statistical difference was found for the other group comparisons. Three eyes in total were enucleated owing to endophthalmitis, post‐traumatic ocular sarcoma, and secondary glaucoma. CONCLUSION: Uveitis in the short‐term and PCO and synechia/dyscoria in the long‐term were the most common complications following phacoemulsification in cats.


title: The history and epidemiology of Middle East respiratory syndrome corona virus

text: Corona viruses cause common cold, and infections caused by corona viruses are generally self-resolving. During the last 4 years, corona viruses have become the most important viruses worldwide because of the occurrence of several recent deaths caused by corona viruses in Saudi Arabia. Spread of the infection occurred worldwide; however, most cases of mortality have occurred in the Middle East. Owing to the predominance of outbreaks in the Middle Eastern countries, the virus was renamed a Middle East respiratory syndrome corona virus (MERS-CoV) by the Corona virus Study Group. The Center for Diseases Control and Prevention and World Health Organization maintain a website that is updated frequently with new cases of MERS-CoV infection. In this review, we describe the history and epidemiology of this novel virus. Studies of the genetics and molecular mechanisms of this virus are expected to facilitate the development of vaccines in the future.


title: Infectious MERS-CoV Isolated From a Mildly Ill Patient, Saudi Arabia

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. We describe isolation of infectious MERS-CoV from the upper respiratory tract of a mildly ill 27-year-old female in Saudi Arabia 15 days after illness onset.


title: Coronavirus Disease 2019: A Gastroenterologist’s Perspective in May 2020

text: We are in the middle of coronavirus disease 2019 (COVID-19) pandemic which has affected every aspect of human life all over the world. Although COVID-19 primarily affects the lungs, it is in fact a multisystem disorder causing high mortality and panicking the whole world. Gastrointestinal (GI) manifestations of this disorder usually accompany respiratory manifestations and this combination is indicative of the severity of the disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, which causes COVID-19, enters the body by attaching to angiotensin converting enzyme-2 receptors which are not only present in the respiratory tract but also in the GI tract. Person-to-person droplet transmission is the main mode of spread although there is potential for fecal-oral transmission. Patients with inflammatory bowel disease (IBD) are not at increased risk of developing COVID-19 and they should continue to take their current medications. If they become positive for SARS-CoV-2 RNA or COVID-19, their biologic therapy should be either delayed or on hold temporarily. GI endoscopy units are high-risk areas and GI procedures are high-risk procedures for the transmission of SARS-CoV-2 infection. Only emergency and semi-emergency procedures should be done, and elective procedures should be temporarily on hold until adequate resources are available. Endoscopists should use appropriate personal protective equipment. Mildly abnormal liver function tests (LFTs) are common in COVID-19 patients and are mostly due to systemic inflammatory response, hepatic ischemia or hepatotoxic medications. Close monitoring of liver function and supportive care of COVID-19 patients are recommended.


title: Which type of cancer patients are more susceptible to the SARS-COX-2: evidence from a meta-analysis and bioinformatics analysis

text: OBJECTIVE: Numerous studies have reported that patients with cancer seem to be more likely to be diagnosed with COVID-19. However, it is still unknown the prevalence of different types of cancer in patients with COVID-19. Therefore, this study will explore which type of cancer patients are more susceptible to the SARS-COX-2. METHODS: Eligible studies were identified by searching several electronic databases for relevant studies published before April 28, 2020. The language was restricted to English or Chinese. The meta-analysis was performed using Stata 12.0. The GEPIA database evaluated the expression of SARS-COX-2 infection key genes in different types of normal and tumor samples. RESULTS: A total of 6 studies, including 205 patients, were identified to be eligible for this meta-analysis. Among the cancer patients infected by SARS-COX-2, the proportion of patients with the lung, colorectal,breast,esophagus,bladder,pancreatic and cervical cancer were 24.7%, 20.5%, 13.0%, 7.6%,7.3%,6.1%,and 6.0%, respectively. These findings were also corroborated by the results of the GEPIA database. CONCLUSION: Compared with other types of cancer, lung cancer and colorectal cancer are more susceptible to SARS-COX-2 infection.


title: Immunopathogenesis of coronavirus infections: implications for SARS

text: At the end of 2002, the first cases of severe acute respiratory syndrome (SARS) were reported, and in the following year, SARS resulted in considerable mortality and morbidity worldwide. SARS is caused by a novel species of coronavirus (SARS-CoV) and is the most severe coronavirus-mediated human disease that has been described so far. On the basis of similarities with other coronavirus infections, SARS might, in part, be immune mediated. As discussed in this Review, studies of animals that are infected with other coronaviruses indicate that excessive and sometimes dysregulated responses by macrophages and other pro-inflammatory cells might be particularly important in the pathogenesis of disease that is caused by infection with these viruses. It is hoped that lessons from such studies will help us to understand more about the pathogenesis of SARS in humans and to prevent or control outbreaks of SARS in the future.


title: Profile–profile comparisons by COMPASS predict intricate homologies between protein families

text: Recently we proposed a novel method of alignment–alignment comparison, COMPASS (the tool for COmparison of Multiple Protein Alignments with Assessment of Statistical Significance). Here we present several examples of the relations between PFAM protein families that were detected by COMPASS and that lead to the predictions of presently unresolved protein structures. We discuss relatively straightforward COMPASS predictions that are new and interesting to us, and that would require a substantial time and effort to justify even for a skilled PSI-BLAST user. All of the presented COMPASS hits are independently confirmed by other methods, including the ab initio structure-prediction method ROSETTA. The tertiary structure predictions made by ROSETTA proved to be useful for improving sequence-derived alignments, because they are based on a reasonable folding of the polypeptide chain rather than on the information from sequence databases. The ability of COMPASS to predict new relations within the PFAM database indicates the high sensitivity of COMPASS searches and substantiates its potential value for the discovery of previously unknown similarities between protein families.


title: Partial Purification of IBV and Subsequent Isolation of Viral RNA for Next-Generation Sequencing

text: RNA viruses are known for a high mutation rate and rapid genomic evolution. As such an RNA virus population does not consist of a single genotype but is rather a collection of individual viruses with closely related genotypes—a quasispecies, which can be analyzed by next-generation sequencing (NGS). This diversity of genotypes provides a mechanism in which a virus population can evolve and adapt to a changing environment. Sample preparation is vital for successful sequencing. The following protocol describes the process of generating a high-quality RNA preparation from IBV grown in embryonated eggs and then partially purified and concentrated through a 30 % sucrose cushion for NGS.


title: Control of the PI3K/Akt pathway by porcine reproductive and respiratory syndrome virus

text: Phosphatidylinositol-3-kinase (PI3K)/Akt is an important cellular pathway that has been shown to participate in various replication steps of multiple viruses. In the present study, we compared the phosphorylation status of Akt during infection of MARC-145 cells and porcine alveolar macrophages (PAMs) with highly pathogenic PRRSV (HP-PRRSV) strain HuN4. We observed that biphasic activation of Akt was induced in at both the early stage (5, 15 and 30 min postinfection) and the late stage (12 and 24 h postinfection) of HP-PRRSV infection of MARC-145 cells, while an early-phase activation of Akt was found exclusively in virus-infected PAMs in vitro. Analysis with the PI3K-specific inhibitor LY294002 confirmed that PI3K acted as the upstream activator for the virus-induced activation of Akt. UV-irradiation-inactivated virus still induced the early event in PAMs but not in MARC-145 cells, suggesting that different mechanisms are employed for the early-stage induction of phosphorylated Akt within different cell cultures. We further demonstrated that FoxO1 and Bad, which serve as downstream targets of Akt, were phosphorylated in virus-infected MARC-145 cells. Moreover, the suppression of phosphorylated Akt with LY294002 significantly inhibited the virus-induced cytopathic effect (CPE) on MARC-145 cells, but it had a negligible effect on virus propagation. Collectively, our data provide new evidence of a novel role for the PI3K/Akt pathway in PRRSV infection of MARC-145 cells.


title: Pandemic preparedness of community pharmacies for COVID-19: A cross-sectional survey

text: BACKGROUND: Community pharmacies provide an important healthcare service, which is broadly established, and constitutes the preferred and initial contact for members of the community. The significant value of community pharmacies was further highlighted during the COVID-19 pandemic crisis. OBJECTIVE: The assessment of community pharmacies preparedness for the COVID-19 pandemic. METHODS: A cross‐sectional interview survey of 1018 community pharmacies working in four regions of Egypt (South, East, Centre, and North). Data collection was conducted from 8–19 April 2020. RESULTS: Availability of personal protective equipment (PPE) and medication was better than alcohol (70% conc.). Home delivery services were available in 49.1% of pharmacies. Infection control measures covering interactions between staff were in place in up to 99.5% of pharmacies. Conversely, there was less frequent availability of contactless payment (29.1%), hand sanitizers (62.1%) or masks (86.5%) for customer use, or a separate area for patients with suspected COVID-19 (64%). Verbal customer education (90.4%) was used preferably to written (81.3%). Despite high clinical knowledge and awareness (97.6%–99.2%), only 8.8% of pharmacists had reported suspected COVID-19 cases, however this varied significantly with pharmacist demographics (geographic region P < 0.001; pandemic training p < 0.001; position p = 0.019; age p = 0.046). CONCLUSIONS: Government and policymakers strive to mitigate the shortage of PPE and medication. More attention should be given to infection control measures around interactions between staff and customers to ensure community pharmacists are fit and able to provide continuity in their important role. Educating customers using regularly-updated posters, banners or signs will contribute to decreasing contact with patients, and reducing the number and duration of visits to the pharmacy. Pandemic preparedness of community pharmacists must also extend to reporting procedures. By avoiding under-reporting or over-reporting, community pharmacists will contribute to accurate monitoring of the national spread of infection.


Right Ventricular Function and Pulmonary Pressures as Independent Predictors of Survival in Patients With COVID-10 Pneumonia


title: Delivery technologies for human vaccines

text: There is currently intense research activity aimed at the development of new delivery systems for vaccines. The goal is to identify optimal methods for presenting target antigens to the immune system in a manner that will elicit immune responses appropriate for protection against, or treatment of, a specific disease. Several different approaches to this general goal have been developed, some are empirical and remain poorly understood, others are more rational, being based, for example, on mimicking natural infections in vivo or on targeting particular features of the immune system. This article will review three categories of delivery systems: (i) adjuvants and formulations; (ii) antigen vectors, including live attenuated micro-organisms and synthetic vectors; and (iii) novel devices for vaccine administration. The review will be restricted to late stage developments in the field of human vaccination.


title: Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review

text: OBJECTIVE: to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. METHOD: for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. RESULTS: the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. CONCLUSIONS: there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed.


title: A call to action for public health nurses during the COVID‐19 pandemic

text: Public health nurses (PHNs) are on the frontline of the public health crisis the world now knows as the COVID-19 pandemic. They serve on mobile strike teams investigating case-contacts, deliver education on self-isolation and quarantine through hotlines and home visits, and interpret the rapidly shifting guidance from the Centers for Disease Control and Prevention (CDC). They are reliable and proven responders during infectious disease emergencies, providing safe, effective, and nondiscriminatory care to the communities in which they serve.


title: Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome

text: Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.


title: Agents and Robots for Collaborating and Supporting Physicians in Healthcare Scenarios

text: Monitoring patients through robotics telehealth systems is an interesting scenario where patients’ conditions, and their environment, are dynamic and unknown variables. We propose to improve telehealth systems’ features to include the ability to serve patients with their needs, operating as human caregivers. The objective is to support the independent living of patients at home without losing the opportunity to monitor their health status. Application scenarios are several, and they spread from simple clinical assisting scenarios to an emergency one. For instance, in the case of a nursing home, the system would support in continuously monitoring the elderly patients. In contrast, in the case of an epidemic diffusion, such as COVID-19 pandemic, the system may help in all the early triage phases, significantly reducing the risk of contagion. However, the system has to let medical assistants perform actions remotely such as changing therapies or interacting with patients that need support. The paper proposes and describes a multi-agent architecture for intelligent medical care. We propose to use the beliefs-desires-intentions agent architecture, part of it is devised to be deployed in a robot. The result is an intelligent system that may allow robots the ability to select the most useful plan for unhandled situations and to communicate the choice to the physician for his validation and permission.


title: Longitudinal study of interventional radiology activity in a large metropolitan Italian tertiary care hospital: how the COVID-19 pandemic emergency has changed our activity

text: OBJECTIVES: To retrospectively analyze interventional radiology (IR) activity changes in the COVID-19 era and to describe how to safely and effectively reorganize IR activity. METHODS: All IR procedures performed between January 30 and April 8, 2020 (COVID-era group) and the same 2019 period (non-COVID-era group) were retrospectively included and compared. A sub-analysis for the lockdown period (LDP: 11 March–8 April) was also conducted. Demographic, hospitalization, clinical, and procedural data were obtained for both groups and statistically compared with univariable analysis. RESULTS: A total of 1496 procedures (non-COVID era, 825; COVID era, 671) performed in 1226 patients (64.9 ± 15.1 years, 618 women) were included. The number of procedures decreased by 18.6% between 2019 and 2020 (825 vs 671, p < .001), with a reduction by 48.2% in LDP (188 vs 363, p < .0001). In the LDP COVID era, bedside procedures were preferred (p = .013), with an increase in procedures from the intensive care unit compared with the emergency department and outpatients (p = .048), and an increased activity for oncological patients (p = .003). No incidents of cross-infection of non-infected from infected patients and no evidence of COVID-19 infection of healthcare workers in the IR service was registered. CONCLUSIONS: Coronavirus disease outbreak changed the interventional radiology activity with an overall reduction in the number of procedures. However, this study confirms that interventional radiology continuum of care can be safely performed also during the pandemic, following defined measures and protocols, taking care of all patients. KEY POINTS: • Coronavirus disease pandemic determined a reduction of interventional radiology activity as compared to the same period of the previous year. • Interventional radiology procedures for life-threatening conditions and non-deferrable oncologic treatments were prioritized as opposed to elective procedures. • Strict adoption of safe procedures allowed us to have until now no incidents of cross-infection of non-infected from infected patients and no evidence of COVID-19 infection of HCWs in the IR service.


title: Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study

text: BACKGROUND. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. METHODS. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. RESULTS. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. CONCLUSIONS. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.


title: Viral Etiology of Influenza-Like Illnesses in Cameroon, January–December 2009

text: Background. No information is available on the viral etiology of upper respiratory tract infections in Cameroon. Methods. We prospectively enrolled outpatients with influenza-like illness (ILI) presenting at 14 sentinel clinics located across the country from January through December 2009. The specimens were tested using real-time and multiplex reverse-transcription polymerase chain reaction methods for the detection of 15 RNA respiratory viruses. Results. We detected at least 1 respiratory virus in 365 of 561 specimens (65.1%). Overall, influenza virus was the most commonly detected virus (28.2% of specimens), followed by human rhinovirus (17.8%); parainfluenza virus (PIV) types 1–4 (7.5%); enterovirus (5.9%); respiratory syncytial virus (RSV; 5.7%); human coronavirus (HCoV) OC43, 229E, NL63, and HKU1 (5.3%); and human metapneumovirus (HMPV; 5.0%). RSV (26 of 31 specimens [83.9%]), PIV (30 of 39 [76.9%]), and HRV (64 of 99 [64.6%]) were most common among children <5 years of age. Coinfections were found in 53 of 365 positive specimens (14.5%), and most (71.7%) were in children <5 years of age. While influenza virus, enterovirus, RSV, and HMPV had a defined period of circulation, the other viruses were detected throughout the year. Conclusions. We found that respiratory viruses play an important role in the etiology of ILI in Cameroon, particularly in children <5 years of age.


title: Interdependent Citizens: The Ethics of Care in Pandemic Recovery

text: The crisis of Covid‐19 has forced us to notice two things: our human interdependence and American society's tolerance for what Nancy Krieger has called “inequalities embodied in health inequities,” reflected in data on Covid‐19 mortality and geographies. Care is integral to our recovery from this catastrophe and to the development of sustainable public health policies and practices that promote societal resilience and reduce the vulnerabilities of our citizens. Drawing on the insights of Joan Tronto and Eva Feder Kittay, we argue that the ethics of care offers a critical alternative to utilitarian and deontological approaches and provides a street‐ready framework for integration into public health deliberations to anchor public policy and investments concerning the recovery and future well‐being of America's citizens and society.


title: Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.


title: EARLY REPORT ON THE IMPACT OF COVID-19 OUTBREAK IN NEUROSURGICAL PRACTICE AMONG MEMBERS OF THE LATIN AMERICAN FEDERATION OF NEUROSURGICAL SOCIETIES

text: Abstract Background The COVID-19 pandemic has caused severe economic consequences by local governmental measures to contain the outbreak1 We provide insight on the impact that healthcare restriction has made on neurosurgical activity in Latin Iberoamerica. METHODS: We performed an internet-based survey among Presidents and Members of the Societies of the Latin American Federation of Neurosurgical Societies (FLANC). We blindly analyzed information about local conditions and their impact on neurosurgical praxis using SPSS® software. Results Information came from 21 countries. Sixteen Society Presidents reported having suspended regular activities, and differing local scheduled congresses, fourteen reported mandatory isolation by government, and four instituted a telemedicine project. Four-hundred eighty-six colleagues, mean age 49 years, reported a mean 79% reduction in their neurosurgical praxis. Seventy-six percent of neurosurgeons had savings to self-support for 3-6 months, if restrictions are long lasting. Conclusions Stopping activities among Societies of the FLANC, together with a drop of 79% of neurosurgical praxis, adds to deficits in provider´s protection equipment and increasing demand for attention in the healthcare systems; representing a huge financial risk for their sustainability. Neurosurgeons should involve in local policies to protect health and economy. Telemedicine represents an excellent solution, avoiding another pandemic of severe diseases across all-specialties as non-essential care can turn essential if left untreated. Financial support and ethics code review is needed to battle this new disease, designated the occupational disease of the decade, that continues to struggle the healthcare systems. Times of crisis are times of great opportunities for humanity to evolve.


title: Adding Colchicine to the Antiretroviral Medication - Lopinavir/Ritonavir (Kaletra) in Hospitalized Patients with Non-Severe Covid-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomized Controlled Trial

text: OBJECTIVES: Colchicine is a well-known drug, which has been used for years to treat a wide range of rheumatic and inflammatory disorders. It helps break the cycle of inflammation through diverse mechanisms including reducing Intereukin-6, Interleukin-8, Tumour Necrosis Factor-alpha besides controlling oxidative stress pathways which all are important and pathologic components in the clinical course and outcome of patients infected with COVID-19. This study aims to assess the anti-inflammatory effects of colchicine in non-severe hospitalized COVID-19 patients. TRIAL DESIGN: Prospective, randomized (1:1 ratio), double blind study with parallel group design. PARTICIPANTS: Hospitalized patients with positive nasopharyngeal swab for COVID-19 infection (RT -PCR) and lung Computed tomography scan involvement compatible with COVID-19 pneumonia. The patients are not severely hypoxic, do not need intubation or invasive oxygenation. Exclusion criteria: known hypersensitivity to colchicine; known hepatic failure; estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m(2) (by the CKD-EPI Creatinine Equation for Glomerular Filtration Rate (GFR) which estimates GFR based on serum creatinine. ; kidney transplant recipients, using Digoxin, QTc >450 msec. Participants will be recruited from inpatients at Labbafinejad Meidcal Center , Tehran, Iran. INTERVENTION AND COMPARATOR: Eligible enrolled patients will be randomized into two groups. Group A will receive the antiretroviral Lopinavir/Ritonavir (Kaletra) while group B will receive Lopinavir/Ritonavir (Kaletra) + Colchicine 1.5 mg loading then 0.5 mg twice daily orally. All patients in both groups will receive the same amounts of essential minerals, vitamins as antioxidants, and antibiotics. Patients of both groups will be treated under optimal treatment based on the CDC and WHO guidelines and national consensus proposed in Iran including the same dosages of Lopinavir/Ritonavir, antibiotics, trace elements and antioxidants while only in group-B patients Colchicine will be added on top of this protocol. MAIN OUTCOMES: Primary: Time for clinical improvement and lung CT score changes 14 days after treatment. Secondary: 14 days after treatment – C-Reactive Protein test x Neutrophil to Lymphocyte Ratio , Interleukin-6, malondialdehyde (MDA) levels reduction – Percentage of patients who require supplemental Oxygen – Mean hospital stay length RANDOMISATION: Patients will be allocated to each group (ratio 1:1) by using an online randomization tool: http://www.graphpad.com/quickcalcs/index.cfm BLINDING (MASKING): This will be a double-blind study in which participants and those assessing the final outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Regarding the pandemic crisis and our center capacity to hospitalize confirmed COVID-19 patients, a total of 80 patients was found to be logical to be randomized into two groups of 40- patients. TRIAL STATUS: Recruitment is ongoing. Recruitment began on 20/03/2020 and the date by which the recruitment is anticipated to be completed is 30/05/2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04360980, registered 24/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Aspectos medicolegales derivados de la pandemia del COVID-19.