title: Bereavement support on the frontline of COVID-19: Recommendations for hospital clinicians

text: Abstract Deaths due to COVID-19 are associated with risk factors which can lead to prolonged grief disorder, post-traumatic stress and other poor bereavement outcomes among relatives, as well as moral injury and distress in frontline staff. Here we review relevant research evidence, and provide evidence-based recommendations and resources for hospital clinicians to mitigate poor bereavement outcomes and support staff. For relatives, bereavement risk factors include dying in an intensive care unit, severe breathlessness, patient isolation or restricted access, significant patient and family emotional distress, and disruption to relatives’ social support networks. Recommendations include advance care planning; proactive, sensitive and regular communication with family members alongside accurate information provision; enabling family members to say goodbye in person where possible; supporting virtual communication; providing excellent symptom management and emotional and spiritual support; and providing and/or sign-posting to bereavement services. To mitigate effects of this emotionally challenging work on staff, we recommend an organisational and systemic approach which includes access to informal and professional support.


title: Phage P22 tailspike protein: crystal structure of the head-binding domain at 2.3 Å, fully refined structure of the endorhamnosidase at 1.56 Å resolution, and the molecular basis of O-antigen recognition and cleavage 1 1 Edited by K. Nagai

text: Abstract The tailspike protein of Salmonella phage P22 is a viral adhesion protein with both receptor binding and destroying activities. It recognises the O-antigenic repeating units of cell surface lipopolysaccharide of serogroup A, B and D1 as receptor, but also inactivates its receptor by endoglycosidase (endorhamnosidase) activity. In the final step of bacteriophage P22 assembly six homotrimeric tailspike molecules are non-covalently attached to the DNA injection apparatus, mediated by their N-terminal, head-binding domains. We report the crystal structure of the head-binding domain of P22 tailspike protein at 2.3 Å resolution, solved with a recombinant telluromethionine derivative and non-crystallographic symmetry averaging. The trimeric dome-like structure is formed by two perpendicular β-sheets of five and three strands, respectively in each subunit and caps a three-helix bundle observed in the structure of the C-terminal receptor binding and cleaving fragment, reported here after full refinement at 1.56 Å resolution. In the central part of the receptor binding fragment, three parallel β-helices of 13 complete turns are associated side-by-side, while the three polypeptide strands merge into a single domain towards their C termini, with close interdigitation at the junction to the β-helix part. Complex structures with receptor fragments from S. typhimurium, S. enteritidis and S. typhi253Ty determined at 1.8 Å resolution are described in detail. Insertions into the β-helix form the O-antigen binding groove, which also harbours the active site residues Asp392, Asp395 and Glu359. In the intact structure of the tailspike protein, head-binding and receptor-binding parts are probably linked by a flexible hinge whose function may be either to deal with shearing forces on the exposed, 150 Å long tailspikes or to allow them to bend during the infection process.


title: Quantitative immunohistochemical assessment of IgA, IgM, IgG and antigen-specific immunoglobulin secreting plasma cells in pig small intestinal lamina propria

text: Abstract Intestinal immune response plays an important defensive role for pathogens, particularly for those transmitted by the oro-faecal route or for foecal shedding modulation. This work examined three parts of intestine from twelve gilts experimentally infected with PCV2-spiked semen, six vaccinated (V group) and six unvaccinated (NV group) against PCV2, 29 and 53 days post infection (DPI). An immunohistochemical investigation for IgA-, IgG- and IgM-antibody bearing plasma cells (PCs) was run on intestinal samples coupled with a sandwich immunohistochemical method to reveal anti-PCV2 antibody-secreting PCs. Plasma cell density was compared in the two groups of animals at 29 and 53 DPI. The IgA, IgG and IgM PC density did not differ between groups but displayed an increase from the upper (villus) to the lower part of the crypts while a decreasing trend in PC density was identified from duodenum to ileum. In the NV group, no increase in anti-PCV2 PC density was demonstrable in the two sampling moment: the amounts of lamina propria PCV2-specific antibody-producing PCs remained constant, 10.55±4.24 and 10.06±5.01 at 29 DPI and 53 DPI, respectively. In the V group a significant increase in PCV2-specific antibody-producing PCs was observed over time. The amounts of PCV2-specific antibody-producing PCs increased from 9.37±13.36 at 29 DPI to 18.76±15.83 at 53 DPI. The data on IgA, IgM and IgG PC counts can be considered reference values in a population of adult pigs. The sandwich method can be proposed as a technique able to identify specific antibody-secreting PCs in formalin-fixed paraffin-embedded tissues. A practical application of the sandwich method is the demonstration of a “booster-like” response of the lamina propria in vaccinated compared to unvaccinated animals. After virus challenge, vaccination induced an increase in the number of PCs containing specific anti-PCV2 antibodies at the level of intestinal mucosa.


title: Hematopoietic cell transplantation and emerging viral infections

text: Viral infections remain important causes of morbidity and mortality in hematopoietic cell transplant recipients. More recent developments in preparative regimens and graft manipulations, as well as the control of well‐recognized post‐transplant infections by the introduction of prophylaxis and preemptive strategies, have influenced the timing and the epidemiology of infections. As new pathogens, such as human metapneumovirus (HMPV), human bocavirus, human coronaviruses HCoV‐NL63 and HCoV‐HKU1, human herpesviruses HHV‐6 and HHV‐7, and polyomaviruses, have emerged, it is fundamental to determine the significance of the newly discovered viruses and their role in the transplantation field. This article summarizes recent data on epidemiology and laboratory diagnosis of new pathogens, as well as clinical features and management of the associated infectious complications. J. Med. Virol. 82:528–538, 2010. © 2010 Wiley‐Liss, Inc.


title: The origin and global emergence of adamantane resistant A/H3N2 influenza viruses

text: Resistance to the adamantane class of antiviral drugs by human A/H3N2 influenza viruses currently exceeds 90% in the United States and multiple Asian countries. Adamantane resistance is associated with a single amino acid change (S31N) in the M2 protein, which was shown to rapidly disseminate globally in 2005 in association with a genome reassortment event. However, the exact origin of influenza A/H3N2 viruses carrying the S31N mutation has not been characterized, particularly in South-East Asia. We therefore conducted a phylogenetic analysis of the HA, NA, and M1/2 segments of viral isolates collected between 1997-2007 from temperate localities in the Northern hemisphere (New York State, United States, 492 isolates) and Southern hemisphere (New Zealand and Australia, 629 isolates) and a subtropical locality in South-East Asia (Hong Kong, 281 isolates). We find that although the S31N mutation was independently introduced at least 11 times, the vast majority of resistant viruses now circulating globally descend from a single introduction that was first detected in the summer of 2003 in Hong Kong. These resistant viruses were continually detected in Hong Kong throughout 2003-2005, acquired a novel HA through reassortment during the first part of 2005, and thereafter spread globally. The emergence and persistence of adamantane-resistant viruses in Hong Kong further supports a source-sink model of global influenza virus ecology, in which South-East Asia experiences continuous viral activity and repeatedly seeds epidemics in temperate areas.


title: Redefining the BH3 death domain as a “Short Linear Motif”

text: BCL-2-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence, the BCL-2 family has expanded to include a nebulous group of non-homologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs), and are diverse in their evolutionary histories. The implied corollaries are that BH3s have a broad phylogenetic distribution and could potentially bind to non-BCL-2-like structural domains with distinct functions.


title: Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study

text: In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129,551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (IQR 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Together, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19. Also, the asymptomatic phase in during recovery of COVID-19 urged that negativity in viral RNA is necessary as de-isolation criteria and follow-up is recommended.


title: Spinal Cryptococcoma in an Immunocompetent Cat

text: Summary This report describes an unusual case of primary cryptococcoma in the proximal thoracic spinal cord of an 11-year-old immunocompetent cat from a farm on which there were large numbers of pigeons. This animal was referred for examination with progressive paralysis and shown to be free from feline immunodeficiency virus, feline leukaemia virus, feline coronavirus and Toxoplasma gondii. It died 2 months later. At necropsy, the only lesion detected was a malacic area, 4cm in length, in the spinal cord. Histopathological examination of the spinal cord revealed severe granulomatous inflammation associated with large numbers of encapsulated yeast cells. In addition to the granulomatous host response, necrosis, digestion chambers, Gitter cells, spheroids and lymphocytic perivascular cuffs were features of the malacic areas. Immunohistochemistry confirmed the presence of Cryptococcus neoformans var. grubii yeast cells.


title: The prevalence of Middle East respiratory Syndrome coronavirus (MERS-CoV) infection in livestock and temporal relation to locations and seasons

text: Abstract Background The Middle East respiratory syndrome (MERS) has been reported for the first time infecting a human being since 2012. The WHO was notified of 27 countries have reported cases of MERS, the majority of these cases occur in the Arabian Peninsula, particularly in Saudi Arabia. Dromedary camels are likely to be the main source of Middle East respiratory syndrome virus (MERS-CoV) infection in humans. Methods MERS-CoV infection rates among camels in livestock markets and slaughterhouses were investigated in Saudi Arabia. A total of 698 nasal swabs were collected and examined with Rapid assay and rtRT-PCR. Ten MERS-CoV positive samples were subjected to full genomic sequencing. In addition, the sensitivity and specificity of the Rapid immunochromatographic assay (BioNote, South Korea) was evaluated as a diagnostic tool for MERS-CoV compared to rtRT-PCR. Results The results showed a high percentage of dromedaries (56.4%) had evidence for nasal MERS-CoV infection. Phylogenetic analysis of the ten MERS-CoV isolates showed that the sequences were closely related to the other MERS-CoV strains recovered from camels and human cases. Moreover, the results showed that 195 samples were positive for MERS-CoV by rapid assay compared to 394 positive samples of rtRT-PCR, which showed low rapid assay sensitivity (49.49%) while, the specificity were found to be 100%. Conclusion These findings indicate that these sites are a highly-hazardous to zoonotic diseases.


title: Clinical and molecular features of adenovirus type 2, 3, and 7 infections in children in an outbreak in Taiwan, 2011

text: Abstract Objectives We studied paediatric patients with human adenovirus (HAdV) infection during the 2011 outbreak in northern Taiwan to define the clinical features of different HAdV genotypes in children. Methods Between January and December 2011, 637 patients <19 years of age exhibited culture-confirmed adenoviral infection in Chang Gung Memorial Hospital, and provided specimens available for genotyping by multiplex real-time PCR. Clinical data were collected retrospectively. Results Excluding five cases with multiple genotypes, 632 cases were included for analysis. Three genotypes were identified, including HAdV-3 (429/632; 67.6%), HAdV-7 (144/632; 22.6%) and HAdV-2 (59/632; 9.8%). Median age was 4.58 years (range 2 months to 18 years), with children infected with HAdV-3 significantly older (82.9% >3 years; p <0.001). Of the 621 inpatients, 98.2% had fevers and all exhibited respiratory symptoms, 75 patients (12.1%) had lower respiratory tract infections, 20 (3.2%) required intensive care (HAdV-2: 1; HAdV-3: 8; and HAdV-7: 11), and three died (all HAdV-7-infected). HAdV-3-infected patients were significantly more likely to have upper respiratory symptoms and a high serum C-reactive protein level >100 mg/L, whereas leucocytosis (white blood cell count >15 000/mm3) was more common in HAdV-2-infected patients (p 0.007). HAdV-7 infections were significantly associated with a longer duration of fever, leucopenia (white blood cell count <5000/mm3), thrombocytopenia (platelet count <150 000/mm3), lower respiratory tract infections, a longer length of hospital stay, and requiring intensive care (all p <0.001). Conclusion Childhood HAdV-2, HAdV-3 and HAdV-7 infections may exhibit different clinical manifestations. Although HAdV-3 was the most prevalent genotype observed during the 2011 Taiwan outbreak, HAdV-7 caused more severe disease characteristics and outcomes.


title: A Case-Control Study Assessing the Impact of Nonventilated Hospital-Acquired Pneumonia on Patient Outcomes

text: Background Nonventilated hospital-acquired pneumonia (NVHAP) is a serious nosocomial infection that is increasingly attributed to antibiotic-resistant bacteria. Methods This is a retrospective case-control study comparing patients with and those without NVHAP from January 1, 2014 to December 31, 2014 at Barnes-Jewish Hospital, a 1,300-bed urban academic medical center in St. Louis, Missouri. Results One hundred seventy-four consecutive patients with NVHAP were enrolled. A random sample of 696 control patients matched by age, sex, race, and hospital admission date were selected from a total of 5,322 potential matched control subjects. NVHAP was pathogen-negative in 98 cases (56.3%). Respiratory viruses were identified in 42 patients (24.1%), gram-negative bacteria were seen in 25 patients (14.4%), and gram-positive bacteria were identified in 20 patients (11.5%). Individuals in whom NVHAP developed were more likely to die (15.5% vs 1.6%; P < .01), to require intensive care (56.3% vs 22.8%; P < .01) or mechanical ventilation (19.0% vs 3.9%; P < 0.01), and to have a longer hospital length of stay (15.9 days [range, 9.8-26.3 days] vs 4.4 days [range, 2.9-7.3 days]; P < 0.01). This case-control study identified a strong association between hospital mortality and NVHAP, with patients who acquired NVHAP having an 8.4 times greater odds of death (95% CI, 5.6-12.5). Conclusions The occurrence of NVHAP was associated with significant increases in mortality, the use of intensive care and mechanical ventilation, and hospital length of stay. We also found that respiratory viruses were an important cause of NVHAP. These findings suggest that efforts aimed at the successful prevention of NVHAP could improve patient outcomes and reduce health-care costs.


title: Strategies for the enhanced intracellular delivery of nanomaterials

text: The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.


title: Rapid, responsive, relevant (R3) research: a call for a rapid learning health research enterprise

text: Our current health research enterprise is painstakingly slow and cumbersome, and its results seldom translate into practice. The slow pace of health research contributes to findings that are less relevant and potentially even obsolete. To produce more rapid, responsive, and relevant research, we propose approaches that increase relevance via greater stakeholder involvement, speed research via innovative designs, streamline review processes, and create and/or better leverage research infrastructure. Broad stakeholder input integrated throughout the research process can both increase relevance and facilitate study procedures. More flexible and rapid research designs should be considered before defaulting to the traditional two-arm randomized controlled trial (RCT), but even traditional RCTs can be designed for more rapid findings. Review processes for grant applications, IRB protocols, and manuscript submissions can be better streamlined to minimize delays. Research infrastructures such as rapid learning systems and other health information technologies can be leveraged to rapidly evaluate new and existing treatments, and alleviate the extensive recruitment delays common in traditional research. These and other approaches are feasible but require a culture shift among the research community to value not only methodological rigor, but also the pace and relevance of research.


title: A double-blind block randomized clinical trial on the effect of zinc as a treatment for diarrhea in neonatal Holstein calves under natural challenge conditions

text: Abstract Diarrhea is the leading cause of death in neonatal calves and contributes to major economic losses. The objective of this double-blind randomized clinical trial was to evaluate the effect of oral inorganic or organic zinc supplementation as a treatment for neonatal diarrhea in calves. Seventy nine 1 to 8 day old male Holstein calves on a California calf ranch were block randomized to one of 3 treatments within 24h from their first onset of diarrhea. Calves received a daily dose of either a placebo composed of 80mg of zinc-free powder, 381.54mg of zinc methionine (Met) (equivalent to 80mg of zinc), or 99.69mg of zinc oxide (ZO) (equivalent to 80mg of zinc) in 2L of a zinc-free oral rehydration solution (ORS). Calves were treated once daily until normal fecal consistency or for a maximum of 14 days. Upon enrollment and exit, calves were weighed, and blood, feces, and liver biopsies were collected for trace mineral analysis. Fecal samples at enrollment and exit were tested for E. coli K99, Cryptosporidium spp., rotavirus and coronavirus. Pre-treatment liver zinc concentrations for the 71 calves in the placebo, zinc Met, and ZO treatment groups were 710.6 (SEM=147.7), 852.3 (SEM=129.6), and 750.7 (SEM=202.9)mg/kg dry weight (DW), respectively. Exit liver zinc concentrations for the calves in the placebo, zinc Met, and ZO treatment groups were 728.9 (SEM=182.9), 1141.0 (SEM=423.8), and 636.8 (SEM=81.5)mg/kg dry weight, respectively. Although statistically non-significant, there were clinically important findings identified for each of zinc Met and ZO treatments. Calves treated with zinc Met gained on average 40g/day during a diarrhea episode compared to a weight loss of 67g/day on average in the placebo-treated calves (Power 19.9%). Calves treated with ZO had 1.4 times higher hazard of clinical cure compared to calves in the placebo group (Power 5.3%). Calves that were fecal positive to cryptosporidium spp. at enrollment and treated with zinc Met had higher odds of testing negative at exit compared to placebo calves (Odds Ratio (OR)=16.0). In contrast, calves treated with ZO tended to recover (fecal score=1) one day earlier compared to calves treated with a placebo (8.5 d vs. 9.7 d). The current trial identified clinically important findings that warrant further research to investigate zinc's therapeutic effect for calf diarrhea.


title: Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study

text: BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.


title: Knowledge and practices of isolation precautions among nurses in Jordan

text: BACKGROUND: Implementation of isolation precautions from the Centers for Disease Control and Prevention (CDC) has been justified through research and clinical evidence. However, nurses' understanding and compliance with these precautions is still unknown. The aim of this study was to assess nurses' knowledge and practices in relation to isolation precautions in Jordan. METHODS: A cross-sectional, descriptive design was used. The study took place in 8 hospitals in Jordan. A self-reported questionnaire and an observational checklist were developed based on the CDC (2007) isolation precautions guidelines. RESULTS: A total of 247 questionnaires were returned out of 400, for a response rate of 61.7%. The results show that most nurses (90%) have good knowledge of isolation precautions. However, only 65% of nurses reported good compliance with isolation precautions. The results of a t test revealed that nurses with Bachelor's degrees perform better in knowledge examinations than nurses with 2-year diplomas (P < .001). However, there was no significant difference in knowledge and self-report practices scores based on nurses' previous training and existence of isolation guidelines in their units or wards (P > .05). The results of the checklists confirm that there is a low compliance with standard isolation practice. In addition, the checklist shows that a high percentage of units and wards do not use isolation signs (46.4%) and posters (34.5%). CONCLUSIONS: This study revealed that educating nurses about isolation is not enough strategy to improve their compliance. It is important to adapt other strategies, such as supporting nurses by giving them a manageable workload, and providing more supplies and reminders of isolation precautions in the hospitals.


title: Isolation and Phylogenetic Characterization of Streptococcus halichoeri from a European Badger (Meles meles) with Pyogranulomatous Pleuropneumonia

text: Summary Clinical and pathological studies in European badgers (Meles meles) are limited. Badgers play a significant role in the epidemiology of bovine tuberculosis (TB) in some countries and an accurate diagnosis is needed for this infection. However, the lesions of bovine TB are similar to those associated with other pathogens, making pathological diagnosis difficult. In the present study, Streptococcus halichoeri was isolated from a European badger with pyogranulomatous pleuropneumonia and suspected of having tuberculosis. TB and other pathogens able to induce similar lesions were ruled out. Comparative 16S rRNA and rpoB gene sequencing studies showed an identity of 99.51% and 98.28%, respectively, with S. halichoeri. This report represents the third description of this bacterium and the first in an animal species other than the grey seal (Halichoerus grypus). It also shows that S. halichoeri can be associated with a pathological process characterized by granulomatous inflammation and resembling tuberculosis.


title: Targeted Deletion of FGL2 Leads to Increased Early Viral Replication and Enhanced Adaptive Immunity in a Murine Model of Acute Viral Hepatitis Caused by LCMV WE

text: Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4(+)CD25(+) Foxp3(+) regulatory T (Treg) cells that inhibits immune activity by binding to FCγRIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2(−/−)) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2(−/−) had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2(+/+)). Frequencies of CD8(+) and CD4(+) T cells producing IFNγ in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2 (−/−) mice. Increased frequencies of CD8(+) T cells specific for LCMV tetramers GP(33) and NP(396) were detected within the liver of fgl2(−/−) mice. Plasma from fgl2(−/−) mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2(−/−) mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses.


Oral hygiene risk factor


title: Extracts of the medicinal herb Sanguisorba officinalis inhibit the entry of human immunodeficiency virus-1

text: Abstract Highly active antiretroviral therapy (HAART) has been successful in reducing human immunodeficiency virus (HIV)-1-associated morbidity and mortality since its introduction in 1996. However, it fails to eradicate HIV-1 infection. The high cost of life-long highly active antiretroviral therapy and the emergence of drug resistance among HIV-1-infected individuals have brought renewed pressure for the discovery of novel antivirals and alternative medicines. Traditional Chinese medicine (TCM) is a complementary and alternative medicine, and serves as a rich resource for new drug development. Despite the almost 100 plant-derived compounds that are in clinical trials, few target HIV-1 infection. In this study, we discovered that Sanguisorba officinalis extract (SOE) has anti-HIV-1 properties. Using a cell-based assay and single-cycle luciferase reporter viruses pseudotyped with envelopes from HIV-1 or control viruses, we found that SOE exhibited significant inhibitory ability against both CCR5 and CXCR4 tropic HIV-1 (ADA and HXB2), with respective IC50 values of 1.91 ± 0.16 μg/mL and 3.70 ± 0.53 μg/mL. SOE also inhibited simian immunodeficiency virus infection but failed to block vesicular stomatitis virus, severe acute respiratory syndrome coronavirus, and influenza H5N1 pseudoviruses. Furthermore, we showed that SOE had no effect on postentry events of HIV-1 replication. Because SOE pretreatment with the virus but not with cell lines expressing viral receptors showed the maximal inhibitory activity, we can state that SOE probably blocks entry by acting on the viral envelope directly. In addition, SOE was able to inhibit reverse transcriptase inhibitor resistant viruses (K103N, Y188L, and K103N/Y188L/G190A) and a protease inhibitor resistant strain (PI-2840). Our findings demonstrate SOE as a novel and specific entry inhibitor, which sheds light on the discovery of anti-HIV-1 drugs from traditional herbal medicines.


29th International Mammalian Genome Conference meeting report


title: Laboratory-based surveillance of hospital-acquired respiratory virus infection in a tertiary care hospital

text: Of 7,772 laboratory-confirmed cases of respiratory viral infection among hospitalized patients, 22.8% were categorized as having hospital-acquired infection. The overall incidence of hospital-acquired respiratory viral infection was 3.9 (95% confidence interval, 3.7-4.1) cases per 1,000 admitted patients. Rhinovirus was the most common virus (30.3%), followed by influenza virus (17.6%) and parainfluenza virus (15.6%).


docid: cakplpzq

title: Emerging Attack and Management Strategies for Nuclear Medicine in Responding to COVID-19—ACNM Member Experience and Advice

text: As the World Health Organization declared COVID-19 as “global pandemic,” it is important for everyone, including nuclear medicine personnel, to know how to stop transmission, contain, and prevent the spread of COVID-19. We reach out to our ACNM (American College of Nuclear Medicine) international members from Wuhan, China and Singapore, who have participated in dealing with COVID-19 for the last 2 months, to learn from their lessons and experiences, so to provide advice to all ACNM members for their clinical practice and management strategies in responding to COVID-19.


title: Adapting Orthopaedic Surgery Training Programs During the COVID-19 Pandemic and Future Directions

text: Abstract The COVID-19 pandemic swept across the world, altering the structure and existence of graduate medical education programs across all disciplines. Orthopaedic residency programs can adapt during these unprecedented times to continue providing meaningful education to trainees, and to continue providing high-quality patient care, all while keeping both residents and patients safe from disease. The purpose of this review is to evaluate the literature and describe evidence-based changes that can be taken to an orthopaedic residency program to ensure patient and resident safety, sustaining the principles of graduate medical education, during the COVID-19 pandemic. We describe measures which can be enacted now or with future pandemics, including workforce and occupational modifications, personal protective equipment, telemedicine, online didactic education, resident wellness, return to elective surgery and factors affecting medical students and fellows. After a review of these strategies, programs can make changes for sustainable improvements and adapt to be ready for second wave events or future pandemics.


title: Bat coronavirus phylogeography in the Western Indian Ocean

text: Bats provide key ecosystem services such as crop pest regulation, pollination, seed dispersal, and soil fertilization. Bats are also major hosts for biological agents responsible for zoonoses, such as coronaviruses (CoVs). The islands of the Western Indian Ocean are identified as a major biodiversity hotspot, with more than 50 bat species. In this study, we tested 1,013 bats belonging to 36 species from Mozambique, Madagascar, Mauritius, Mayotte, Reunion Island and Seychelles, based on molecular screening and partial sequencing of the RNA-dependent RNA polymerase gene. In total, 88 bats (8.7%) tested positive for coronaviruses, with higher prevalence in Mozambican bats (20.5% ± 4.9%) as compared to those sampled on islands (4.5% ± 1.5%). Phylogenetic analyses revealed a large diversity of α- and β-CoVs and a strong signal of co-evolution between CoVs and their bat host species, with limited evidence for host-switching, except for bat species sharing day roost sites. Importance This is the first study to report the presence of coronaviruses (CoVs) in bats in Mayotte, Mozambique and Reunion Island, and in insectivorous bats in Madagascar. Eight percent of the tested bats were positive for CoVs, with higher prevalence in continental Africa than on islands. A high genetic diversity of α- and β-CoVs was found, with strong association between bat host and virus phylogenies, supporting a long history of co-evolution between bats and their associated CoVs in the Western Indian Ocean. These results highlight that strong variation between islands does exist and is associated with the composition of the bat species community on each island. Future studies should investigate whether CoVs detected in these bats have a potential for spillover in other hosts.


docid: acrkbzey

title: Neutralization of genotype 2 porcine epidemic diarrhea virus strains by a novel monoclonal antibody

text: Abstract Porcine epidemic diarrhea virus (PEDV) has two genotypes, G1 and G2. To research the immunogenicity differences of PEDV G1 and G2 genotype strains and obtain a neutralizing monoclonal antibody (mAb), we inoculated specific-pathogen-free BALB/c mice with a newly emerged strain, PEDV-LNCT2. After immunizations, cells from the spleen of the mice were fused with SP2/0 myeloma cells. Following culturing and subcloning, a strain, 1B9, secreting neutralizing antibody, was obtained. The 1B9 mAb neutralized new variant genotype 2 PEDV strains (LNCT2, LNSY, and Hjms), but it did not neutralize a genotype 1 PEDV strain (CV777), in vitro. Results showed that the epitope recognized by the 1B9 mAb lies in the spike protein, and that it is a conformational epitope. These findings confirm that allelic differences in the PEDV S gene between the G1 and G2 genotype strains led to changes in the S protein and, thus, differences in its immunogenicity.


title: Innate immunity for biodefense: A strategy whose time has come

text: Defense against biothreat agents requires a broad-spectrum approach. Modulation of the innate immune system might fulfill this requirement. Hackett's previous review of innate immune activation as a broad-spectrum biodefense strategy identified several unresolved questions. The current article is a systematic approach to answering those questions with the focused participation of research groups developing this technology. Our team of academic and industry participants reviewed the promising agents and came to the following conclusions. It is feasible to construct a biodefense platform combining synergistic agents that activate the innate immune system against a broad range of pathogens on the basis of conserved microbial components by using a nasal spray for immune activation in the respiratory and gastrointestinal tracts because these are the most likely routes of attack. It might also be possible to include agents that inhibit molecular events leading to septic shock. Innate immune-activating agents designed to activate Toll-like and other receptors will probably provide protection against the biothreat pathogen spectrum for periods ranging from 2 to 14 days for IFNs up to 26 weeks for immunomodulatory oligonucleotides. Initial treatment is proposed on the first index case or biosensor alert. Boost doses would be required. Harmful inflammation is possible, but thus far, only transient fever has been observed. Autoimmune reaction and retroviral activation have not been seen thus far in preclinical and human trials of many of these compounds. Toll-like receptor agonists caused cytokine production in all subjects tested, but genetic polymorphism reduced the response to IFN in African American subjects.


title: COVID 19 in babies: Knowledge for neonatal care

text: Infection is a leading cause of death worldwide in babies under one month of age who are more susceptible to sepsis due to immature host defence mechanisms. Usually, babies may become acutely unwell from infective pathogens due to specific differences in their respiratory and immune systems. However, with the Covid-19 virus, the focus of this paper, it appears that the neonatal population is not significantly affected in the same way as adults. That said, knowledge about this novel virus is rapidly emerging. Therefore, it is vital that neonatal nurses, midwives and other healthcare professionals are adequately informed and educated about the potential impact on neonatal practice. This review paper draws upon key findings and themes from a selection of recent literature to provide an overview of current knowledge on Covid-19 and the implications for care within the neonatal field. The discussion focuses on the nature of Covid-19, its pathophysiology and transmission relevant to maternal and neonatal care. This is followed by implications for practice; namely, maternal issues, the importance of human breast milk, neonatal care relating to parenting and specific management before a final review of the current World Health Organization guidance.


title: Missouri K-12 school disaster and biological event preparedness and seasonal influenza vaccination among school nurses

text: BACKGROUND: School preparedness for bioevents, such as emerging infectious diseases, bioterrorism, and pandemics, is imperative, but historically has been low. METHODS: The Missouri Association of School Nurses members were sent an online survey during the 2013-2014 school year to assess current bioevent readiness. There were 15 and 35 indicators of school disaster and bioevent preparedness, respectively. Multivariate linear regressions were conducted to delineate factors associated with higher school disaster and bioevent preparedness scores. RESULTS: In total, 133 school nurses participated, with a 33.6% response rate. On average, schools had fewer than half of the disaster or bioevent indicators. Disaster and bioevent preparedness scores ranged from 1-12.5 (mean, 6.0) and 5-25 (mean, 13.8), respectively. The least frequently reported plan components included bioterrorism-specific psychological needs addressed (1.5%, n = 2), having a foodservice biosecurity plan (8.3%, n = 11), and having a liberal sick leave policy for bioevents (22.6%, n = 30). Determinants of better bioevent preparedness include perception that the school is well prepared for a pandemic (P = .001) or natural disaster (P < .05), nurse being on the disaster planning committee (P = .001), and school being a closed point of dispensing (P < .05). CONCLUSION: Schools are underprepared for biological events and are not on track to meet state and national biological preparedness goals.


title: Sensitivity and specificity of in vitro diagnostic device used for influenza rapid test in Taiwan

text: Abstract The pandemic influenza A/H1N1 outbreak resulted in 18,449 deaths in over 214 countries. In Taiwan, the influenza rapid test, an in vitro diagnostic device (Flu-IVD), only requires documented reviews for market approval by the Taiwan Food and Drug Administration. The purpose of this study was to investigate the analytical sensitivity and specificity of Flu-IVDs used in Taiwan. Analytical sensitivity and specificity tests were performed for influenza antigens A/California/7/2009 (H1N1) virus, A/Victoria/210/2009 (H3N2) virus, B/Brisbane/60/08 virus, and human coronavirus OC43. A total of seven domestic and 31 imported Flu-IVD samples were collected, of which, 20 samples had inadequate labeling, including those with removed package inserts or incorrect insert information. The analytical sensitivity of Flu-IVDs for A/H1N1, A/H3N2, and Flu B was 500–1000 ng/mL, 1000 ng/mL, and 1000 ng/mL, respectively. For the 50% cell culture infective dose (CCID50) label, the average A/H1N1 and A/H3N2 sensitivity for Flu-IVDs was log10 5.8 ± 0.5 and log10 6.6 ± 0.5 CCID50/mL, respectively. As to the specificity test, no product cross-reacted with human coronavirus OC43. This study provides important information on the Flu-IVD regulation status and can thus help the government formulate policies for the regulation of in vitro diagnostic devices in Taiwan.


title: Pneumonia in children in the developing world: New challenges, new solutions

text: Pneumonia has been a leading cause of death in both developed and developing countries as long as health indicators have been available. Yet the issues of concern for this syndrome are far from static. Improvements in access to health services have lowered infant mortality rates, benefiting children around the world and lowering the fraction of child deaths caused by pneumonia. However, progress has been interrupted repeatedly by the emergence of new pathogens. Landmark randomized controlled trials have now demonstrated the effectiveness of Haemophilus influenzae type b (Hib) and multivalent pneumococcal conjugate vaccines against childhood pneumonia, as well as meningitis and bacteremic disease. Momentum has gathered to tackle long-standing economic obstacles to expand access to new vaccines and programs for the poorest countries of the world. A pressing challenge for the control of pneumonia in developing countries is to identify better metrics for pneumonia. Surveillance tools are needed that will bridge studies of interventions, establish preventable disease burden, and serve as indicators for monitoring new programs.


title: Recent advances on host plants and expression cassettes' structure and function in plant molecular pharming

text: Plant molecular pharming is a promising system to produce important recombinant proteins such as therapeutic antibodies, pharmaceuticals, enzymes, growth factors, and vaccines. The system provides an interesting alternative method to the direct extraction of proteins from inappropriate source material while offering the possibility to overcome problems related to product safety and source availability. Multiple factors including plant hosts, genes of interest, expression vector cassettes, and extraction and purification techniques play important roles in the plant molecular pharming. Plant species, as a biosynthesis platform, are a crucial factor in achieving high yields of recombinant protein in plant. The choice of recombinant gene and its expression strategy is also of great importance in ensuring a high amount of the recombinant proteins. Many studies have been conducted to improve expression, accumulation, and purification of the recombinant protein from molecular pharming systems. Re-engineered vectors and expression cassettes are also pivotal tools in enhancing gene expression at the transcription and translation level, and increasing protein accumulation, stability, retention and targeting of specific organelles. In this review, we report recent advances and strategies of plant molecular pharming while focusing on the choice of plant hosts and the role of some molecular pharming elements and approaches: promoters, codon optimization, signal sequences, and peptides used for upstream design, purification and downstream processing.


COVID‐19 and Anxiety and Depression in 2020


title: The phenylalanine ammonia-lyase gene family in Isatis indigotica Fort.: molecular cloning, characterization, and expression analysis

text: Abstract Phenolic compounds, metabolites of the phenylpropanoid pathway, play an important role in the growth and environmental adaptation of many plants. Phenylalanine ammonia-lyase (PAL) is the first key enzyme of the phenylpropanoid pathway. The present study was designed to investigate whether there is a multi-gene family in I. Indigotic and, if so, to characterize their properties. We conducted a comprehensive survey on the transcription profiling database by using tBLASTn analysis. Several bioinformatics methods were employed to perform the prediction of composition and physicochemical characters. The expression levels of IiPAL genes in various tissues of I. indigotica with stress treatment were examined by quantitative real-time PCR. Protoplast transient transformation was used to observe the locations of IiPALs. IiPALs were functionally characterized by expression with pET-32a vector in Escherichia colis strain BL21 (DE3). Integration of transcripts and metabolite accumulations was used to reveal the relation between IiPALs and target compounds. An new gene (IiPAL2) was identified and both IiPALs had the conserved enzymatic active site Ala-Ser-Gly and were classified as members of dicotyledon. IiPAL1 and IiPAL2 were expressed in roots, stems, leaves, and flowers, with the highest expression levels of IiPAL1 and IiPAL2 being observed in stems and roots, respectively. The two genes responded to the exogenous elicitor in different manners. Subcellular localization experiment showed that both IiPALs were localized in the cytosol. The recombinant proteins were shown to catalyze the conversion of L-Phe to trans-cinnamic acid. Correlation analysis indicated that IiPAL1 was more close to the biosynthesis of secondary metabolites than IiPAL2. In conclusion, the present study provides a basis for the elucidation of the role of IiPALs genes in the biosynthesis of phenolic compounds, which will help further metabolic engineering to improve the accumulation of bioactive components in I. indigotica.


title: Imaging manifestations and pathological analysis of severe pneumonia caused by human infected avian influenza (H7N9)

text: Abstract Objective To investigate the imaging and pathological findings of severe pneumonia caused by human infected avian influenza (H7N9), and therefore to further understand and improve diagnostic accuracy of severe pneumonia caused by human infected avian influenza (H7N9). Methods The relevant clinical and imaging data of 19 cases, including 10 males and 9 females, with pneumonia caused by human infected avian influenza (H7N9) was retrospectively analyzed. One of the cases had received percutaneous lung biopsy, with the clinical, imaging and pathological changes possible to be analyzed. Results The lesions were mainly located at lower lobes and dorsal of lungs, involving multiple lobes and segments. Ground-glass opacities and/or pulmonary opacities were the more often imaging manifestations of severe pneumonia caused by human infected avian influenza (H7N9) in early and evolving phases (19/19,100%). By biopsy following percutaneous lung puncture, exudation of slurry, cellulose, RBC and neutrophils, formation of hyaline membrane, squamous metaplasia and organizing exudates were observable at the alveolar space. Some of alveoli collapsed, and some responded to show compensatory emphysema. Conclusion The imaging features of severe pneumonia caused by human infected avian influenza (H7N9) include obvious ground-glass opacity and pulmonary consolidation, mainly at lower lobes and dorsal of lungs, with rapid changes. The cross-analysis of imaging and pathology preliminary can elucidate the pathological mechanisms of ground-glass opacities and pulmonary consolidation of severe pneumonia. Such an intensive study is beneficial to prompt clinicians to observe and evaluate the progress of the disease. In addition, it is also in favor of managing the symptoms and reducing the mortality rate.


title: Anticardiolipin antibodies and COVID‐19—A case report from America

text: In an effort to unravel the pathological mechanism of COVID-19, several reports and studies have been recently conducted in the frontlines around the world. Some initial clues have been obtained, and among them, the concern for clot formation and the idea of an impaired coagulation has strongly increased. We report a case of pulmonary embolism in a COVID-19 patient who tested positive for anticardiolipin antibodies. This article is protected by copyright. All rights reserved.


title: Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind

text: Pangolins are of conservation concern as one of the most heavily poached, yet least understood mammals. The Sunda pangolin (Manis javanica) in particular is a critically endangered species. Here, we investigate the behaviour of these pangolins, for the first time, using a battery of cognitive tasks based on a manipulation of available sensory information. In an object-choice task in which only one of two containers was baited with food, the pangolins were able to find the food with olfactory information alone (N = 2), but not with visual or acoustic information alone (N = 1). The single subject tested on all three domains was further tested on how he used smell to find food by providing him with an opportunity to find it from a controlled distance or by using scent trails as a guide. The results suggest that our subject may have the capacity to exploit scent trails left by prey which can be tracked to a final source, though we found no evidence to suggest that he had the ability to initiate hunts based on distant prey odors. Despite the small sample size, this is the first controlled experiment to investigate pangolin foraging behaviour and cognition, which may have implications for the future protection of pangolin habitat based on the location of prey species.


Increased rates of respiratory viral (RV) infections using Flocked Swabs and UTM-RT


title: Aptamers: Uptake mechanisms and intracellular applications

text: Abstract The structural flexibility and small size of aptamers enable precise recognition of cellular elements for imaging and therapeutic applications. The process by which aptamers are taken into cells depends on their targets but is typically clathrin-mediated endocytosis or macropinocytosis. After internalization, most aptamers are transported to endosomes, lysosomes, endoplasmic reticulum, Golgi apparatus, and occasionally mitochondria and autophagosomes. Intracellular aptamers, or “intramers,” have versatile functions ranging from intracellular RNA imaging, gene regulation, and therapeutics to allosteric modulation, which we discuss in this review. Immune responses to therapeutic aptamers and the effects of G-quadruplex structure on aptamer function are also discussed.


Chinese institute makes bold sequencing play


title: Mild versus severe COVID-19: laboratory markers

text: Abstract The number of COVID-19 patients is increasing dramatically worldwide and treatment in intensive care units (ICU) has become a major challenge, the early recognition of severe forms of is absolutely essential for timely triaging of patients. While the clinical status, in particular Peripheral oxygen saturation (SpO2) levels and concurrent comorbidities of COVID-19 patients largely determines the need of their admittance to ICUs, several laboratory parameters may facilitate the assessment of disease severity. In hospitalized patients, clinicians should consider low lymphocyte count as well as the serum levels of CRP, D-dimers, ferritin and IL-6 which may be used in risk stratification to predict severe and fatal COVID-19. The more several or all of these parameters are altered, the more likely it is that the course of the disease will be unfavourable.


title: Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n-propanol, acetonitrile or 1,4-dioxane)+water

text: Abstract The equilibrium solubility of ribavirin in solvent mixtures of {methanol (1)+water (2)}, {n-propanol (1)+water (2)}, {acetonitrile (1)+water (2)} and {1,4-dioxane (1)+water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1kPa). At the same temperature and mass fraction of methanol (n-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol+water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. The preferential solvation parameters for methanol, n-propanol, acetonitrile or 1,4-dioxane (δx 1,3) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.


title: Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus

text: We have identified a series of 1-aryl-4,6-diamino-1,2-dihydrotriazines, structurally related to the antimalarial drug cycloguanil, as new inhibitors of influenza A and B virus and respiratory syncytial virus (RSV) via targeting of the host dihydrofolate reductase (DHFR) enzyme. Most analogues proved active against influenza B virus in the low micromolar range, and the best compounds (11, 13, 14 and 16) even reached the sub-micromolar potency of zanamivir (EC(50) = 0.060 μM), and markedly exceeded (up to 327 times) the antiviral efficacy of ribavirin. Activity was also observed for two influenza A strains, including a virus with the S31N mutant form of M2 proton channel, which is the most prevalent resistance mutation for amantadine. Importantly, the compounds displayed nanomolar activity against RSV and a superior selectivity index, since the ratio of cytotoxic to antiviral concentration was >10,000 for the three most active compounds 11, 14 and 16 (EC(50) ∼0.008 μM), far surpassing the potency and safety profile of the licensed drug ribavirin (EC(50) = 5.8 μM, SI > 43).


title: Using Latent Class Analysis to Identify the Complex Needs of Youth on Probation

text: Youth involved with the juvenile justice system have higher rates of unmet social and psychological service needs than the general population. Yet, scant research has addressed the potentially complex needs of youth on probation. This study is thus a first step in improving our ability to promote positive youth development and improved outcomes from youth on probation. It uses administrative data on probation youth from FY2011-2013 in a mid-Atlantic state. We estimated latent class models based on the ordinal scoring (high, moderate, none/low) of the 25 subscales from a standardized assessment administered at intake. In order to test whether groups were distinct, we examined a range of variables, including the official risk classification and recidivism rates measured by officieal rearrests and reconvictions. We report the demographic differences between the estimated groups, as well as adverse childhood experiences, school and employment status, previous legal history, and substance use history. Ultimately, the seven-class model produced four groups that others have noted: a relatively low needs (lowest need), relatively high needs (complex needs), substance use service needs, and mental health service needs. The other three groups that emerged include two gender specific groups (one for male and one for female high-need groups) and a group with skills needs that lacks supportive and protective skills. The analyses will facilitate a better appreciation for the service needs of moderate risk youth. Youth on probation are not a uniform population; they reflect tremendous heterogeneity, and probation systems should embrace systemic responsivity to provide appropriate services to improve youth outcomes. Advancing efforts to provide a broader spectrum of services that address multi-morbid conditions can ensure that youth have opportunities to improve their quality of life during the period of supervision.


title: Prevalence of Isospora suis and Eimeria spp. in suckling piglets and sows in Poland

text: Abstract The aim of this investigation was to determine the prevalence of coccidian infections in suckling piglets and sows in Poland. The research was carried out in 14 out of 16 Polish provinces in the years 2003–2005. The investigation was conducted on three types of farms: large farms (>100 sows), medium farms (25–100 sows) and small farms (<25 sows). Diarrhoea of unweaned piglets was observed on all the examined farms. Overall, 780litters of suckling piglets from 104 farms and 267 mother sows were examined. The faeces were analyzed with the modified McMaster method. Isopsora suis was found in 217 (27.8%) litters from 70 (66.7%) farms. Eimeria spp. was detected only in 20 (2.6%) litters from 12 (11.5%) farms. On the large farms I. suis infection was detected in 31.7% of litters whereas Eimeria spp. in 1.4% of them. On the medium sized farms I. suis was found in 18.1% of litters and Eimeria spp. in 0.6%. On the small farms I. suis was detected in only 13.2% of litters, whereas Eimeria spp. in as many as 28.9%. I. suis and Eimeria spp. oocysts were found in 18 (6.7%) and 16 (6%) sows respectively. From 72 sows producing I. suis infected piglets only 12 (16.7%) shed I. suis oocysts and as little as 4 (5.6%) shed Eimeria oocysts. In the remaining 56 sows (77.8%) no cases of coccidian infections were detected. The results of this investigation demonstrate the high prevalence of I. suis in suckling piglets on the large swine farms in Poland.


title: Coronavirus 2019 and health systems affected by protracted conflict: the case of Syria

text: Abstract Introduction Two thirds of countries globally are unprepared to respond to a health emergency as per the International Health Regulations (2005) with conflict-affected countries like Syria particularly vulnerable. Political influences on outbreak preparedness, response and reporting may also adversely affect control of SARS-CoV-2 in Syria. Syria reported its first case on 22 March 2020 however concerns were raised that this was delayed and that underreporting continues. Main Syria's conflict has displaced more than half its pre-war population leaving 6.7 million people internally displaced; consequent overcrowding with insufficient water, sanitation and healthcare (including laboratory capacity) could lead to conditions which are ideal for spread of SARS-CoV-2 in Syria. Political changes have led to the formation of at least three health systems within Syria's borders, each with their own governance, capacity and planning. This fragmentation with little interaction between them could lead to poor resource allocation and adversely affect control. As such, COVID-19 could overwhelm the health systems (particularly intensive care capacity) leading to high deaths across the population, particularly for the most vulnerable such as detainees. Conclusions Locally implementable interventions which rapidly build WASH and health system capacity are required across Syria to ensure early detection and management of COVID-19 cases.


title: Effects of coronavirus (COVID-19) pandemic on orthopedic residency program in the seventh largest city of the world: Recommendations from a resource-constrained setting

text: The coronavirus (COVID-19) pandemic has hit the entire world hard. Since its inception from Wuhan China the whole world is affected now. Health care facilities and workers are overwhelmed and the situation is changing on daily basis. With the changes in the dynamics of the hospitals, residency and fellowships training programs have also suffered undoubtedly. Due to decreased elective cases and outpatient clinics surgical training gets compromised, however on the other side this physical distancing and isolation have proven to be effective measures in controlling the disease. In this article we share our experience of effect of COVID-19 pandemic on our orthopedic residency program and how we coped along with it. We also discussed some way forwards in the article.


Which medical specialties should be prioritised to fill staffing gaps caused by COVID‐19 in the United Kingdom? A network analysis


title: RT-PCR Detection of Avian Coronaviruses of Galliform Birds (Chicken, Turkey, Pheasant) and in a Parrot

text: Of the many primer combinations that we have investigated for the detection of avian coronaviruses, two have worked better than any of the others: they worked with the largest number of strains/samples of a given coronavirus and the most species of avian coronavirus, and they also produced the most sensitive detection tests. The primer combinations were: oligonucleotide pair 2Bp/4Bm, which is in a region of gene 1 that is moderately conserved among all species of coronavirus (1); and UTR11-/UTR41+, which are in a highly conserved part of the 3′ untranslated region of avian coronaviruses related to infectious bronchitis virus (2). The gene 1 primer pair enabled the detection of a new coronavirus in a green-cheeked Amazon parrot (Amazon viridigenalis Cassin). In this chapter we describe the use of these oligonucleotides in a one-step (single-tube) RT-PCR, and describe the procedure that we used to extract RNA from turkey feces.


title: Serological characterization of guinea pigs infected with H3N2 human influenza or immunized with hemagglutinin protein

text: BACKGROUND: Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA) protein were studied. RESULTS: Serological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI), and recognition of linear epitopes by peptide scanning (PepScan). Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes. CONCLUSIONS: Infection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.


title: Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression

text: OBJECTIVES: To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir. METHODS: We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China. RESULTS: Of ten patients, secondary, tertiary and quartus patients emerged; the incubation period was 3–7 days. Mainly initial symptoms were cough and low fever (37.3–38.0 °C). An asymptomatic case presented normal radiography, the others had ground glass opacities. All cases (three transferred, seven discharged) were exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir because of adverse effects, two of them deteriorated, one was hospitalized longer than others who with sustained lopinavir use. Levels of potassium, albumin, and lymphocytes were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3–14, 6–8 and 7–9 days, respectively. CONCLUSIONS: Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir use. More research on a larger scale is needed to verify these points.


title: Identification of bovine viral diarrhea virus receptor in different cell types

text: Abstract Anti-idiotypic antibodies (anti-ids) have been used successfully in studies on bovine viral diarrhea virus (BVDV) receptor(s) in our laboratory. The anti-ids specifically bound to cultured cells and identified a 50 kDa cellular membrane protein, which is thought to be a specific receptor for BVDV. In this study, flow cytometric analyses demonstrated that the anti-ids also specifically bound to different cell types, namely MDBK, EBK, BT, PK15, MA104, and Vero. Experiments on virus attachment and replication showed that BVDV adsorbed to all cells and replicated in them except monkey kidney cells MA104 and Vero (non-permissive). Results from plaque reduction assays indicated that cellular membrane proteins from all cell lines competitively inhibited BVDV attachment to cultured MDBK cells, suggesting the presence of BVDV receptor on all cells. Immunoblotting of cell membrane proteins with the anti-ids revealed a 50 kDa protein in both permissive and nonpermissive cells. Subcloned or synchronized MDBK cells demonstrated no significant difference of binding with anti-ids as compared to normal cultured cells.


title: COVID-19: Immunology and treatment options

text: Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.


title: COVID‐19: a global threat to the nervous system

text: In less than 6 months, the severe acute respiratory syndrome‐coronavirus type 2 (SARS‐CoV‐2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID‐19) also involves multiple other organs including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS‐CoV‐2 infection is rapidly accumulating. These may result from a variety of mechanisms including virus‐induced hyper‐inflammatory and hypercoagulable states, direct virus infection of the CNS, and post‐infectious immune mediated processes. Example of COVID‐19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis and endothelialitis. In the peripheral nervous system COVID‐19 is associated with dysfunction of smell and taste, muscle injury, the Guillain‐Barre syndrome and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID‐19 poses a global threat to the entire nervous system. While our understanding of SARS‐CoV‐2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID‐19.


title: Genomic Characteristics and Changes of Avian Infectious Bronchitis Virus Strain CK/CH/LDL/97I after Serial Passages in Chicken Embryos

text: BACKGROUND: We previously attenuated the infectious bronchitis virus (IBV) strain CK/CH/LDL/97I and found that it can convey protection against the homologous pathogenic virus. OBJECTIVE: To compare the full-length genome sequences of the Chinese IBV strain CK/CH/LDL/97I and its embryo-passaged, attenuated level to identify sequence substitutions responsible for the attenuation and define markers of attenuation. METHODS: The full-length genomes of CK/CH/LDL/97I P5 and P115 were amplified and sequenced. The sequences were assembled and compared using the MEGALIGN program (DNAStar) and a phylogenetic tree was constructed using MEGA4 software. RESULTS: The CK/CH/LDL/97I virus population contained subpopulations with a mixture of genetic mutants. Changes were observed in nsp4, nsp9, nsp11/12, nsp14, nsp15, nsp16, and ORF3a, but these did not result in amino acid substitutions or did not show functional variations. Amino acid substitutions occurred in the remaining genes between P5 and P115; most were found in the S region, and some of the nucleotide mutations resulted in amino acid substitutions. Among the 9 nsps in the ORF1 region, nsp3 contained the most nucleotide substitutions. CONCLUSIONS: Sequence variations in different genes, especially the S gene and nsp3, in the genomes of CK/CH/LDL/97I viruses might contribute to differences in viral replication, pathogenicity, antigenicity, immunogenicity, and tissue tropism.


docid: bwllypvq

title: High-resolution melting curve analysis for infectious bronchitis virus strain differentiation

text: BACKGROUND AND AIM: Belonging to the Coronaviridae family, avian infectious bronchitis virus (IBV) causes respiratory, reproductive, and renal diseases in poultry. Preventative measures lie mainly in vaccination, while the gold standard for IBV classification and differentiation is based on the sequence analysis of the spike 1 (S1) gene. In this study, we tested a new assay for IBV strain classification that is less expensive and requires reduced time and effort to perform. We carried out a quantitative real-time polymerase chain reaction followed by high-resolution melting (qRT-PCR/HRM) curve analysis. MATERIALS AND METHODS: In this study, qRT-PCR was conducted on a partial fragment S1 gene followed by a high resolution melting curve analysis (qRT-PCR/HRM) on 23 IBV-positive samples in Jordan. For this assay, we utilized the most common IBV vaccine strains (Mass and 4/91) as a reference in the HRM assay. To evaluate the discrimination power of the qRT-PCR/HRM, we did the sequencing of the partial S1 gene. RESULTS: It was shown that HRM was able to classify IBV samples into four clusters based on the degree of similarity between their melting points: The first cluster exhibited the highest similarity to the 4/91 strain, while the second was similar to the Mass-related IBV strain. Although the third cluster contained the highest number of samples, it displayed no similarity to any of the reference vaccine strains, and, after comparing them with the sequencing results, we found that the samples in the third cluster were similar to the variant II-like (IS-1494-06) IBV field strain. Finally, the fourth cluster comprised one unique sample that was found to belong to the Q1 IBV strain. CONCLUSION: Our developed qRT-PCR/HRM curve analysis was able to detect and rapidly identify novel and vaccine-related IBV strains as confirmed by S1 gene nucleotide sequences, making it a rapid and cost-effective tool.


Malaria in travellers in the time of corona


title: COVID-19 related stress exacerbates common physical and mental pathologies and affects treatment (Review)

text: COVID-19 pandemic has caused a global public health emergency resulting in unprecedented individual and societal fear and anxiety. The stress surrounding this biothreat appears to have clinical implications in all aspects of medicine, both in mental and physical health spheres. The impact of COVID-19 related anxiety in Cardiology, Paediatrics, Oncology, Dermatology, Neurology and Mental Health and how it affects treatments is discussed. Moreover, the need for introducing novel communication and therapeutic approaches is highlighted in the new landscape of the COVID-19 era.


title: The treatment of rhinovirus infections: progress and potential

text: The common cold is an important illness both as a result of the economic impact of this common disease and because of the morbidity associated with the complications of the illness. Recent attempts to develop antiviral treatments for the common cold represent a substantial advance over previous efforts. Formidable barriers remain to be overcome, however, before any of these new products will be proven to be clinically useful. Recent advances in our understanding of the pathogenesis of common cold symptoms have provided insights into potential new targets for the treatment of this illness.


title: Shedding Light on Dysphagia Associated With COVID-19: The What and Why

text: The most common symptom of COVID-19 in critically ill patients is ARDS (acute respiratory distress syndrome), with many patients requiring invasive or noninvasive respiratory support in the intensive care unit. Oropharyngeal dysphagia may be a consequence of the respiratory-swallowing incoordination common in ARDS or may occur following the respiratory support interventions. In this commentary, we highlight the risk and complications of oropharyngeal dysphagia in patients with COVID-19 and urge medical and rehabilitation professionals to consider dysphagia a prognostic complication, provide appropriate referrals, and initiate early interventions as appropriate.


title: Status of Infection Prevention and Control in Tanzanian Primary Health Care Facilities: Learning From Star Rating Assessment

text: Abstract Background The WHO estimates 10-30% of hospital admissions are associated with poor infection prevention and control (IPC). There are no reliable data on IPC status in Tanzanian healthcare facilities; hence the Star Rating Assessment (SRA) was established to address this. This study compared the health facility performances on adherence to IPC principles using baseline and reassessment data of SRA. Methods A retrospective analysis of data from eight randomly selected regions across Tanzania. Data was gathered from an SRA database in which records of baseline assessments (2015/16) and reassessments (2017/18) were documented. Each healthcare facility’s ownership and service level were investigated as independent variables. Results A total of 2,131 healthcare facilities at baseline and 2,185 at reassessment were analysed. Median adherence to IPC principles increased from 31% (IQR: 20%, 46%) to 57% (IQR: 41.4%, 73.2%) after interventions (p<0.001). Privately-owned facilities had higher adherence to IPC principles compared to publicly-owned facilities during baseline (p<0.001) however, the difference was not significant after intervention (p=0.751). On average, hospitals scored highest followed by health centres and then dispensaries during both assessments. Being a privately-owned facility was a predictor of attaining a recommended IPC score of 80% at baseline (POR=1.92 CI=1.06-3.48) but not after the intervention. Facility level was not a predictor during baseline assessment; however after intervention hospitals were twice as likely to attain the recommended score compared to dispensaries (POR=2.27 CI=1.15-4.45) Conclusion Assessment and rating of quality and organization of health services plus management support to healthcare facilities, leads to improved adherence to IPC principles.


title: Transforming Public Health Law: The Turning Point Model State Public Health Act

text: Law is an essential tool for improving public health infrastructure and outcomes; however, existing state statutory public health laws may be insufficient. Built over decades in response to various diseases/conditions, public health laws are antiquated, divergent, and confusing. The Turning Point Public Health Statute Modernization National Collaborative addressed the need for public health law reform by producing a comprehensive model state act. The Act provides scientifically, ethically, and legally sound provisions on public health infrastructure, powers, duties, and practice. This article examines (1) how statutory law can be a tool for improving the public's health, (2) existing needs for public health law reform, (3) themes and provisions of the Turning Point Act, and (4) how it is being used by public health practitioners.


title: Procalcitonin and C-reactive protein in severe 2009 H1N1 influenza infection

text: PURPOSE: To examine whether, in an adult intensive care unit (ICU), procalcitonin or C-reactive protein (CRP) levels discriminated between 2009 H1N1 influenza infection and community-acquired pneumonia of bacterial origin. METHODS: A retrospective observational study performed at an Australian hospital over a 4-month winter period during the 2009 H1N1 influenza pandemic. Levels on admission of procalcitonin and CRP were compared between patients admitted to the ICU with community-acquired pneumonia of bacterial and 2009 H1N1 origin. RESULTS: Compared to those with bacterial or mixed infection (n = 9), patients with 2009 H1N1 infection (n = 16) were significantly more likely to have bilateral chest X-ray infiltrates, lower APACHE scores, more prolonged lengths of stay in ICU and lower white cell count, procalcitonin and CRP levels. Using a cutoff of >0.8 ng/ml, the sensitivity and specificity of procalcitonin for detection of patients with bacterial/mixed infection were 100 and 62%, respectively. A CRP cutoff of >200 mg/l best identified patients with bacterial/mixed infection (sensitivity 100%, specificity 87.5%). In combination, procalcitonin levels >0.8 ng/ml and CRP >200 mg/l had optimal sensitivity (100%), specificity (94%), negative predictive value (100%) and positive predictive value (90%). Receiver-operating characteristic curve analysis suggested the diagnostic accuracy of procalcitonin may be inferior to CRP in this setting. CONCLUSIONS: Procalcitonin measurement potentially assists in the discrimination between severe lower respiratory tract infections of bacterial and 2009 H1N1 origin, although less effectively than CRP. Low values, particularly when combined with low CRP levels, suggested bacterial infection, alone or in combination with influenza, was unlikely.


title: Chapter 7 Biofiltration technique for removal of waterborne pathogens

text: Abstract Pathogenic agents such as protozoa, bacteria, virus, and helminths disseminate among human community via ingestion of contaminated water and pose a serious concern to public health. Biological filtration method of disinfection is the key step in centralized multistep and decentralized point-of-use water treatment system. A biofilm of indigenous microorganisms fixed on solid surface, called biofilter, is an eco-friendly and economic technique for removal of pollutants and pathogens. Stone, gravel, sand, soil, compost, mesoporous mineral stone, wood chips, etc., exemplify solid bed medium which provide enhanced surface area for microbial adherence and water retention. Slow sand filter (SSF) characterized by slow flow rate (0.1–0.2m3/h) and a biological layer over filter bed called schmutzdecke is fairly efficient in removal of coliform microorganisms such as Giardia, Cryptosporidium, Salmonella, Escherichia coli, total coliform and fecal coliform, fecal streptococci, bacteriophage, and MS2 virus from wastewater. Rapid sand filter characterized by coarser sand and higher flow rate than SSF removes indicator microorganisms efficiently. Stormwater biofilter is popular and effective method for removal of pathogen and involves biological activity and physical retention of pathogen on filter media. Microbial diversity, inoculum size, pH and moisture of medium, temperature, and nutrient content are key parameters governing optimum performance of biofilter system. Therefore, biofiltration can be an efficient bioremediation technology for pathogen removal.


title: Profile of specific antibodies to SARS-CoV-2: The first report

text: • Profile of specific antibodies to virus in blood can assist diagnosis and reflect disease course. • The preliminary study explored the dynamic profile of IgM and IgG. • Serum IgM to SARS-COV-2 last more than a month indicating the prolonged virus replication in infected patients.


title: Computational tools for viral metagenomics and their application in clinical research

text: Abstract There are 100 times more virions than eukaryotic cells in a healthy human body. The characterization of human-associated viral communities in a non-pathological state and the detection of viral pathogens in cases of infection are essential for medical care and epidemic surveillance. Viral metagenomics, the sequenced-based analysis of the complete collection of viral genomes directly isolated from an organism or an ecosystem, bypasses the “single-organism-level” point of view of clinical diagnostics and thus the need to isolate and culture the targeted organism. The first part of this review is dedicated to a presentation of past research in viral metagenomics with an emphasis on human-associated viral communities (eukaryotic viruses and bacteriophages). In the second part, we review more precisely the computational challenges posed by the analysis of viral metagenomes, and we illustrate the problem of sequences that do not have homologs in public databases and the possible approaches to characterize them.


title: Is SARS-CoV-2 Vertically Transmitted?

text: At the end of 2019, in Wuhan (China), the onset of a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed. The disease, named COVID-19, has a wide spectrum of clinical presentations, ranging from asymptomatic or mild to critical, and for some patients the disease is even fatal. Apparently, being a child or being pregnant does not represent an additional risk for adverse outcomes. The purpose of this mini-review was to investigate what is in the scientific literature, so far, in regard to vertical transmission of SARS-CoV-2. Data were obtained independently by the two authors, who carried out a systematic search in the PubMed, Embase, LILACS, Cochrane, Scopus and SciELO databases using the Medical Subject Heading terms “coronavirus,” “COVID-19,” and “vertical transmission.” Few studies about the vertical transmission of SARS-CoV-2 are found in the literature. In all case reports and case series, the mothers' infection occurred in the third trimester of pregnancy, there were no maternal deaths, and most neonates had a favorable clinical course. The virus was not detected in the neonate nasopharyngeal swab samples at birth, in the placenta, in the umbilical cord, in the amniotic fluid, in the breast milk or in the maternal vaginal swab samples in any of these articles. Only three papers reported neonatal SARS-CoV-2 infection, but there is a bias that positive pharyngeal swab samples were collected at 36 h and on the 2nd, 4th, and 17th days of life. The possibility of intrauterine infection has been based mainly on the detection of IgM and IL-6 in the neonates' serum. In conclusion, to date, no convincing evidence has been found for vertical transmission of SARS-CoV-2.


title: Discovery of modulators of HIV-1 infection from the human peptidome

text: Almost all human proteins are subject to proteolytic degradation, which produces a broad range of peptides that have highly specific and sometimes unexpected functions. Peptide libraries that have been generated from human bodily fluids or tissues are a rich but mostly unexplored source of bioactive compounds that could be used to develop antimicrobial and immunomodulatory therapeutic agents. In this Innovation article, we describe the discovery, optimization and application of endogenous bioactive peptides from human-derived peptide libraries, with a particular focus on the isolation of endogenous inhibitors and promoters of HIV-1 infection. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro3312) contains supplementary material, which is available to authorized users.


title: Malaria in Children

text: Malaria remains widespread throughout the planet and increasing global travel continues to lead to imported cases of malaria in travelers, including children. This article provides an overview of pediatric malaria, including its epidemiology, clinical features, diagnosis, treatment, and prevention in travelers.


Síndrome de tako-tsubo asociado con COVID-19


title: Spectrum of bactericidal action of amylmetacresol/2,4-dichlorobenzyl alcohol lozenges against oropharyngeal organisms implicated in pharyngitis

text: PURPOSE: Pharyngitis is commonly caused by a self-limiting upper respiratory tract infection (URTI) and symptoms typically include sore throat. Antibiotics are often inappropriately used for the treatment of pharyngitis, which can contribute to antimicrobial resistance, therefore non-antibiotic treatments which have broad antiseptic effects may be more appropriate. Amylmetacresol (AMC) and 2,4-dichlorobenzyl alcohol (DCBA) are present in some antiseptic lozenges and have established benefits in providing symptomatic relief and some in vitro antiviral action. METHODS: Seven bacterial species associated with pharyngitis, namely Streptococcus pyogenes, Fusobacterium necrophorum, Streptococcus dysgalactiae subspecies equisimilis, Moraxella catarrhalis, Haemophilus influenza, Arcanobacterium haemolyticum and Staphylococcus aureus, were exposed to an AMC/DCBA lozenge dissolved in artificial saliva. In vitro bactericidal activity was measured as a log reduction in colony-forming units (CFUs). RESULTS: Bactericidal activity was recorded against all organisms after 1 minute. Greater than 3 log(10) reductions in CFUs were observed at 1 minute for S. pyogenes (log(10) reduction CFU/mL ± SD, 5.7±0.1), H. influenza (6.1±0.1), A. haemolyticum (6.5±0.0) and F. necrophorum (6.5±0.0), at 5 minutes for S. dysgalactiae (6.3±0.0) and M. catarrhalis (5.0±0.9) and at 10 minutes for S. aureus (3.5±0.1). CONCLUSION: An AMC/DCBA lozenge demonstrated a greater than 99.9% reduction in CFUs against all tested species within 10 minutes, which is consistent with the time a lozenge remains in the mouth. Patients with uncomplicated bacterial pharyngitis may benefit from the antibacterial action of antiseptic AMC/DCBA lozenges. Furthermore, AMC/DCBA lozenges may be more relevant and appropriate than antibiotics for pharyngitis associated with a self-limiting viral URTI.


title: Spontaneous dog osteoarthritis — a One Medicine vision

text: Osteoarthritis (OA) is a global disease that, despite extensive research, has limited treatment options. Pet dogs share both an environment and lifestyle attributes with their owners, and a growing awareness is developing in the public and among researchers that One Medicine, the mutual co-study of animals and humans, could be beneficial for both humans and dogs. To that end, this Review highlights research opportunities afforded by studying dogs with spontaneous OA, with a view to sharing this active area of veterinary research with new audiences. Similarities and differences between dog and human OA are examined, and the proposition is made that suitably aligned studies of spontaneous OA in dogs and humans, in particular hip and knee OA, could highlight new avenues of discovery. Developing cross-species collaborations will provide a wealth of research material and knowledge that is relevant to human OA and that cannot currently be obtained from rodent models or experimentally induced dog models of OA. Ultimately, this Review aims to raise awareness of spontaneous dog OA and to stimulate discussion regarding its exploration under the One Medicine initiative to improve the health and well-being of both species.


title: Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft

text: Abstract Objectives To evaluate ureteral replacement by a free homologous graft of acellular matrix in a rat model. Methods In 30 male Sprague-Dawley rats, a 0.3 to 0.8-cm midsegment of the left ureter was resected and replaced with an acellular matrix graft of equal length placed on a polyethylene stent. The animals were killed at varying intervals, and the grafted specimens were prepared for light and electron microscopy. Results In all animals, the acellular matrix graft remained in its original position without evidence of incrustation or infection, and histologic examination showed complete epithelialization and progressive infiltration by vessels. At 10 weeks, smooth muscle fibers were observed; at 12 weeks, nerve fibers were first detected; at 4 months, smooth muscle cells had assumed regular configuration. Conclusions The ureteral acellular matrix graft appears to promote the regeneration of all ureteral wall components.


COVID‐19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms?


China’s ‘mask diplomacy’ to change the COVID-19 narrative in Europe


title: A Review of Coronavirus Infection in the Central Nervous System of Cats and Mice

text: Feline infectious peritonitis (FIP) is a common cause of death in cats. Management of this disease has been hampered by difficulties identifying the infection and determining the immunological status of affected cats and by high variability in the clinical, pathological, and immunological characteristics of affected cats. Neurological FIP, which is much more homogeneous than systemic effusive or noneffusive FIP, appears to be a good model for establishing the basic features of FIP immunopathogenesis. Very little information is available about the immunopathogenesis of neurologic FIP, and it is reasonable to use research from the well‐characterized mouse hepatitis virus (MHV) immune‐mediated encephalitis system, as a template for FIP investigation, and to contrast findings from the MHV model with those of FIP. It is expected that the immunopathogenic mechanisms will have important similarities. Such comparative research may lead to better understanding of FIP immunopathogenesis and rational prospects for management of this frustrating disease.


title: Absence of neutralizing activity in serum 1 year after successful treatment with antivirals and recovery from MERS in South Korea

text: We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. The neutralizing activity in serum was measured by pseudovirus inhibition assays. Three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection.


title: Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar

text: BACKGROUND: The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases. METHODOLOGY: Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status. PRINCIPAL FINDINGS: A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections. CONCLUSIONS: These results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar.


title: Mutagenesis of the murine hepatitis virus nsp1-coding region identifies residues important for protein processing, viral RNA synthesis, and viral replication

text: Abstract Despite ongoing research investigating mechanisms of coronavirus replication, functions of many viral nonstructural proteins (nsps) remain unknown. In the current study, a reverse genetic approach was used to define the role of the 28-kDa amino-terminal product (nsp1) of the gene 1 polyprotein during replication of the coronavirus murine hepatitis virus (MHV) in cell culture. To determine whether nsp1 is required for MHV replication and to identify residues critical for protein function, mutant viruses that contained deletions or point mutations within the nsp1-coding region were generated and assayed for defects in viral replication, viral protein expression, protein localization, and RNA synthesis. The results demonstrated that the carboxy-terminal half of nsp1 (residues K124 through L241) was dispensable for virus replication in culture but was required for efficient proteolytic cleavage of nsp1 from the gene 1 polyprotein and for optimal viral replication. Furthermore, whereas deletion of nsp1 residues amino-terminal to K124 failed to produce infectious virus, point mutagenesis of the nsp1 amino-terminus allowed recovery of several mutants with altered replication and RNA synthesis. This study identifies nsp1 residues important for protein processing, viral RNA synthesis, and viral replication.