We encountered a challenging case of endovascular repair for distal stent graft-induced new entry (SINE) using the AFX aortic cuff. Postoperative computed tomography revealed no endoleak with a preferable conformation change of the externally mounted graft material of the AFX cuff against the tear.

Intraprosthetic regurgitation (IR) is a rare but devastating complication of transcatheter aortic valve implantation (TAVI). We describe the successful treatment of moderate intraprosthetic regurgitation in a 89 year old woman, who had been treated for severe aortic stenosis using a 23mm SAPIEN-3 valve.

In tetanus patients Levodopa and Carbidopa combination (which is usually used to relieve the signs of extrapyramidal) causes respiratory muscles spasm relief thereby the need for sedatives is decreased and patient saved later on via central nervous system mechanism, by providing the inhibitory neurotransmitters at Anterior Horn cells.

To the editor, Chronic eosinophilic pneumonia (CEP) is an idiopathic disease rarely reported in children1,2. It typically occurs in non-smoking, middle age females and the diagnosis requires exclusion of systemic or primary eosinophilic lung diseases1,2. The triad of pulmonary symptoms (usually for >2 weeks), abnormal chest radiographic findings and eosinophilia in the blood and/or pulmonary tissue in the absence of an alternative etiology is highly suggestive of CEP. Patients may present with cough (90-93%) dyspnea (50-90%), fever (77-87%), night sweats (23%), weight loss (57-75%), rhinitis or sinusitis (6-24%), chest pain (8-16%), hemoptysis (8-10%), and weakness/fatigue1,2. An asthma phenotype is present in roughly a third to 3/4 of patients. Bilateral peripheral consolidative infiltrates are seen on chest radiograph (CXR) with computed tomography (CT) showing peripheral airspace disease and reactive hilar adenopathy1,2. Peripheral eosinophilia is almost universal with cell counts routinely higher than 1000/mm3 and more than half of patients also have an elevated IgE2. Eosinophilia on the bronchoalveolar lavage (BAL) ranges from 12 to 95% with a mean of 58%2. The triad of pulmonary symptoms, radiographic findings and eosinophilia in CEP typically respond to prednisone within a few days2. Initial doses range from 0.5 to 1mg/kg/day and may be tapered after clinical/radiographic improvement. Duration of therapy depends on the response and is highly variable, with a mean of 19 months but a range of 0.5 to 96 months1. Relapse is common, occurring in up 50% of patients2. While the pathogenesis of CEP is not fully understood, the underlying mechanism undoubtedly involves eosinophils and likely shares inflammatory pathways with asthma, which is why it may be amenable to treatment with novel biologic therapies approved for asthma. Although there are case reports of patients with CEP who were treated with either omalizumab or mepolizumab, there are no reports of treatment with dupilumab3.  However, there is a report of a patient possibly experiencing CEP as a consequence of dupilumab4.             We present the case of an 11-year-old, previously healthy, African American female who presented with fever, cough, dyspnea, chest pain and decreased appetite of 3 months duration. Her past medical history was significant for pneumonia three months prior that failed to resolve with antibiotics.  She was subsequently prescribed albuterol and treated as an outpatient with a working diagnosis of asthma. Her symptoms persisted and she was ultimately hospitalized with chronic pneumonia of unclear etiology.  Her family and social histories were unremarkable.  She strongly denied vaping or inhalant abuse. Her physical exam was remarkable for bilateral coarse crackles, signs of respiratory distress and reproducible chest pain. Her CXR showed bilateral consolidative opacities and her CT demonstrated bilateral lymphadenopathy and multilobar consolidation (see Figures 1 &2). Her initial lab work was remarkable for a white blood cell count of 10,000/µL (3.84-9.84/µL) with 10% (0-4%) peripheral eosinophilia, erythrocyte sedimentation rate of 103 mm/hr (0-15mm/hr), and C reactive protein of 7mg/dL (0.00-0.50mg/dL). She was treated with 14 days of antibiotics without clinical improvement. During the course of follow up her FEV1 declined > 35% and she developed a severe persistent asthma phenotype.  She was evaluated for tuberculosis, allergic bronchopulmonary aspergillosis, helminth infection, eosinophilic granulomatosis with polyangitis, sarcoidosis, and immunodeficiency however her work up was negative. She underwent bronchoscopy, which demonstrated significant bilateral lower airway casts that were 93% eosinophilic. She was treated with high dose prednisone for 4 weeks and improved for a few months, however her symptoms returned. She continued oral prednisone intermittently for approximately 22 months without improvement and was deemed refractory to therapy.  Repeat imaging during that time demonstrated persistent opacities and she developed bronchiectasis.  Repeat bronchoscopies revealed return of mucoid impactions. Throughout her course, she continued to have eosinophilia in the blood (ranging from 0.4 to 13%) and on BAL (ranging from 9-93%).  She was then treated with pulse methylprednisolone and daily cyclosporine in an attempt to gain clinical remission which resulted in modest improvement of symptoms. She continued daily cyclosporine with the addition of dupilumab every 2 weeks for 6 months. Following the addition of dupilumab significant clinical and radiographic improvement were noted within 2 weeks.   Her cyclosporine was subsequently weaned without recurrence of symptoms and she remains symptom free with marked improvement in her Chest X-ray findings for over 12 months on subcutaneous dupilumab injections q 2 weeks. Dupilumab is an injectable humanized IgG4 monoclonal antibody, approved for home use in patients with eosinophilic or steroid dependent asthma, which targets IL-4α receptors and inhibits IL-4 and IL-13 binding. It has been shown to reduce the frequency of asthma exacerbations, improve FEV1 and reduce oral steroid use in patients with severe asthma5.  This is the first report of dupilumab as a therapy to treat CEP and the first report of monoclonal antibody therapy to treat CEP in a pediatric patient. Dupilumab may be an alternative for CEP that is refractory to corticosteroids or that requires prolonged therapy. It may also be a more convenient therapy compared to other monoclonal antibodies available to patients because it can be administered at home.  References1. Jederlinic PJ, Sicilian L, Gaensler EA. 1988. Chronic eosinophilic pneumonia. A report of 19 cases and a review of the literature. Medicine (Baltimore). 67(3):154-162.2. Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF. 1998. Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The groupe d'etudes et de recherche sur les maladies "orphelines" pulmonaires (germ"o"p). Medicine (Baltimore). 77(5):299-312.3. Lin RY, Santiago TP, Patel NM. 2019. Favorable response to asthma-dosed subcutaneous mepolizumab in eosinophilic pneumonia. J Asthma. 56(11):1193-1197.4. Menzella F, Montanari G, Patricelli G, Cavazza A, Galeone C, Ruggiero P, Bagnasco D, Facciolongo N. 2019. A case of chronic eosinophilic pneumonia in a patient treated with dupilumab. Ther Clin Risk Manag. 15:869-875.5. Castro M, Rabe KF, Corren J, Pavord ID, Katelaris CH, Tohda Y, Zhang B, Rice MS, Maroni J, Rowe P et al. 2020. Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. ERJ Open Res. 6(1).

Education in ecology and evolution often utilizes field instruction to teach key learning outcomes. Remote teaching of learning outcomes that have been traditionally taught in the field, necessitated by the COVID-19 pandemic, presents unique challenges for students, instructors, and institutions. A survey of 117 faculty conducted during spring 2020 revealed substantial reduction of learning outcomes typically taught in the field, and frequent substitutions of less active and more instructor-centered remote activities for field activities. The survey revealed generally negative instructor views on many remote teaching substitutions, yet also showed several approaches that instructors regarded as more effective, despite potential challenges with equitably teaching them. I suggest several models of remote substitutions for traditional field teaching of identification, field techniques, data collection, and study design in the context of the results of this survey.

The coronavirus disease of 2019 (COVID-19) pandemic has impacted educational systems worldwide, in particular primary and secondary schooling. To enable students of the local secondary school in Brisbane, Queensland, to continue with their practical agricultural science learning and facilitate online learning, a small-scale citizen science project was designed and rapidly implemented as a collaboration between the school and a multidisciplinary university research group focused on pollen allergy. Here we reflect on the process of developing and implementing this project from the perspective of the school and the university. A learning package including modules on pollen identification, tracking grass species, measuring field greenness, using a citizen science data entry platform, forensic palynology, as well as video guides, risk assessment and feedback forms were generated. Junior agriculture science students participated in the learning via online lessons and independent data collection in their own local neighborhood and/or school grounds situated within urban environments. The project provided useful data on local distribution and flowering of grass species. The experience allowed two-way knowledge exchange between the secondary and tertiary education sectors. The unique context of restrictions imposed by the social isolation policies as well as Public Health and Department of Education directives, allowed the team to respond by adapting teaching and research activity to develop and trial learning modules and citizen science tools. The project provided a focus to motivate and connect teachers, academic staff, and school students during a difficult circumstance. Extension of this citizen project for the purposes of research and secondary school learning, has the potential to offer ongoing benefits for grassland ecology data acquisition and student exposure to real-world science.

BACKGROUND: The burden of disease generated by acute bronchiolitis (AB) in infants is unknown in developing countries. Evidence on the disease burden is important for decision-making processes within the health sector. The objective of the present study is to determine the Disability-Adjusted Life Years in a middle-income country METHODS: DALYs were calculated, using the methodology of Global Burden of Disease Study, for the following health outcomes of AB: AB uncomplicated, AB with complications, AB with severe complications, with long term complications. To estimate the DALY of each outcome, we performed a systematic review of evidence and complemented with information from the national epidemiological surveillance system. Sensibility analysis was made using a bootstrapped method with 10000 iterations in package DALY calculator of R program. RESULTS: In 2019, we estimated that 482 993 years of life (IC 95% 366 565- 690 294) were lost due to AB in infants. The rate of DALYs estimated for AB with mild complications were 19 DALYs / 1000 person-year, 6 DALYs / 1000 person-year for AB with severe complications, 6 DALYs / 1000 person-year for AB uncomplicated CONCLUSION: The burden of AB is a serious problem in Colombia, with a considerable social impact in terms of disability and mortality. It is necessary novel pharmacological strategies to minimize the impact of this serious problem in Colombia.

The increasingly wide application of chloroplast(cp) genome super-barcode in taxonomy and the recent breakthrough in cp genetic engineering make the development of new cp gene resources urgent and significant. Corydalis is recognized as the most genotypes complicated and taxonomically challenging plant taxa in Papaveraceae. However, no complete cp genome for this genus has been reported to date. In this study, we sequenced four complete cp genomes of two endangered lithophytes Corydalis saxicola and C. tomentellav in Corydalis, conducted a comparative genomics study on them, and a highly variable cp genome structure was found. The cp genomes have a large genome size of 189,029 to 190,247 bp, possessing a quadripartite structure and with two highly expanded inverted repeat (IR) regions (length: 41,955 to 42,350 bp). Comparison between the cp genomes of C. tomentella, C. saxicola and Papaveraceae species, five NADH dehydrogenase-like genes (ndhF, ndhD, ndhL, ndhG, ndhE) with psaC, rpl32, ccsA and trnL-UAG normally located in the SSC region have migrated to IRs, resulting in IR expansion and gene duplication. An up to 9 kb inversion involving five genes (rpl23, ycf2, ycf15, trnI-CAU and trnL-CAA) was found within IR regions. The accD gene was found to be absent and the ycf1 gene has shifted from the IR/SSC border to the SSC region as a single copy. Phylogenetic analysis based on the sequences of common CDS showed that the genus Corydalis is quite distantly related to the other genera of Papaveraceae, it provided a new clue for recent advocacy to establish a separate Fumariaceae family. Our results revealed one special cp genome structure in Papaveraceae, provided a useful resources for classification of the genus Corydalis, and will be valuable for understanding Papaveraceae evolutionary relationships.

Objective: Investigate in-patients weight loss during hospital stay. Methods: In a retrospective study carried out with 170 in-patients, weight loss during hospitalization and its relationship with the type of disease, diet therapy, subjective global assessment (SGA), nutritional risk screening (NRS), anthropometry and hospitalization time (HT) were investigated. The Chi-square test, the Mann-Whitney and the univariate and multiple Cox regression analysis were used. Results: During hospitalization 41.18% patients experienced weight loss. Patients who were overweight experienced a higher rate of weight loss while in the ward (45.7% of patients; p=0.0179). Patients who were overweight, were twice as likely to lose weight during hospitalization, when compared with those who were already underweight (p= 0.0339; HR = 2.312; CI % = 1.066; 5.018). The age, gender, disease, diet prescribed during hospitalization, SGA, NRS, anthropometry and fasting time were not considered risk factors associated with weight loss. Conclusion: There was no influence of the dietary therapy type on weight loss. Only those patients who were overweight according to BMI were more associated to lose weight during hospitalization.

The current COVID-19 pandemic has forced the global higher education community to rapidly adapt to partially- or fully-online course offerings. For field- or lab-based courses in ecological curricula, this presents unique challenges. Fortunately, a diverse set of active learning techniques exist, and these techniques translate well to online settings. However, limited guidance and resources exist for developing, implementing, and evaluating active learning assignments that fulfil specific objectives of ecology-focused courses. To address these informational gaps, we (1) identify broad learning objectives across a variety of ecology-focused courses, (2) provide examples, based on our collective online teaching experience, of active learning activities that are relevant to the identified ecological learning goals, and (3) provide guidelines for successful implementation of active learning assignments in online courses. Using The Wildlife Society’s list of online higher education ecology-focused courses as a guide, we obtained syllabi from 45 ecology-focused courses, comprising a total of 321 course-specific learning objectives. We classified all course-specific learning objectives into at least one of five categories: (1) Identification, (2) Application of Concepts/Hypotheses/Theories, (3) Management of Natural Resources, (4) Development of Professional Skills, or (5) Evaluation of Concepts/Practices. We then provided two examples of active learning activities for each of the five categories, along with guidance on their implementation in online settings. We suggest that, when based on sound pedagogy, active learning techniques can enhance the online student’s experience by activating ecological knowledge; moreover, active learning techniques should also be incorporated into in-person offerings once the current COVID-19 crisis has abated.

Now, we know that the first report of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was in December 2019 in Wuhan, China. In January, the existence of a disease caused by a virus with respiratory tropism for humans was announced, and in February it was already named SARS-Cov-2. The World Health Organization (WHO) 1 gave it the name of COVID-19, on February 11. One month later, WHO declared that the disease caused by this virus was already a pandemic (WHO, 2020)1. The virus started in China, then affected other Asian countries such as Japan, South Korea, etc., and later spread to Europe, then America.As this pandemic progresses, the reports of this six-month period show that this SARS-CoV-2 coronavirus not only targets the respiratory system, its effect on the cardiovascular, digestive, and renal apparatus has also been described. In addition, recent reports have described a set of neurological symptoms 2-4. Furthermore, the presence of this virus in the neurons and the capillary endothelium of the frontal cortex was seen in a patient who died of SARS-CoV-24. Moreover, other reports have shown its presence in the brainstem and in the cerebrospinal fluid (CSF) of other patients with SARS-CoV-2 5-6. Recent reports suggested that the cells with the expression of the angiotensin-converting enzyme 2 (ACE-2) may be a target for this coronavirus, since ACE 2 is a suggested cellular receptor for this coronavirus 4,7-8. Interestingly, various reports have demonstrated the presence of ACE-2, in both neurons and glial cells 7,9-11. Consequently, the evidence suggests that central nervous system (CNS) may be a target organ for this virus. It is known that the presence of this virus is responsible for the inflammatory process, which causes damage not only at the pulmonary level, but also at the cardiovascular, renal, and digestive system levels. All of these structures have a great regenerative capacity and thus reduce the damage in the long term. However, an inflammatory process at the CNS level could leave sequelae that, with age, could favor the early appearance of neurodegenerative processes, such as Alzheimer’s disease, Parkinson’s disease, vascular type dementia, multiple sclerosis etc., 12-13. Consequently, preventive measures should be taken to avoid the CNS from suffering future damage.Autopsy of patients with COVID-19 has shown that the brain tissue is hyperemic, edematous, and has degenerated neurons 2,7. However, it is necessary to know the percentage of cases in which there were changes in the nervous tissue caused by SARS-CoV-2, the types of modifications and the CNS regions most affected by COVID\sout-19. Data can help us know the impact on the brain tissue of this viral infection. In addition to supporting the neuroinvasive effect on the CNS and peripheral nervous system (PNS) of this coronavirus, there are the reported cases of meningitis, encephalitis, and Guillain-Barré syndrome associated with SARS-CoV-2 7,14-17.The clinical picture of SARS-CoV-2 is very wide, with symptoms and signs that involve the respiratory, cardiovascular, renal, digestive, and hepatic systems. However, there are also symptoms in which the CNS and PNS could be involved 2,3. Neurological manifestations have been classified as non-specific and specific by various authors2,15,18-20. Among the non-specific ones are headache, fatigue, dyspnea, etc. While the specific ones imply clear CNS or PNS affection data, such as loss of smell and reduction of taste and vision, neural pain, epileptic seizures, acute cerebrovascular disease, and deterioration of the state of consciousness have also been reported3,14,15,17,19,20.The way in which the SARS-CoV-2 can reach neurons and glial cells is through the blood crossing the blood-brain barrier or by retrograde transport through peripheral nerves. There is evidence for both hypotheses. At the beginning of the disease, patients with COVID-19 may have alterations or loss of smell and taste, probably because the virus may damage this pathway, which has been reported to recover, in some cases at the end of the disease and in others up to several weeks after the patient recovered 20. The virus can pass through the olfactory pathway, which enters the brain through the cribiform plate (transcribial route) 5,7,21. This route has been reported for other viruses, including SARS-CoV7,18,22. In addition, various reports have detected various viruses with respiratory tropism, including some coronaviruses, can reach the brain by retrograde transport, due to their neurotropic properties 5,7,21,22.Moreover, there is a percentage of patients who enter the ICU and require ventilatory assistance, since they do not breathe spontaneously7,21,23. Consequently, it is necessary to study whether this effect of COVID-19 is due to direct action on lung tissue or due to its neurotoxicity at the level of the brainstem, by affecting the respiratory center, which responds to changes in blood pH and CO2 levels 24.In summary, more studies are required to obtain additional information on the neurotoxic effects of COVID-19. However, with the aforementioned data, we can suggest that this coronavirus has neurotropic properties with neuroinvasive activity, which should be investigated, looking for therapeutic tools to reduce the damage that could be left at the nervous tissue level.ReferencesWorld Health Organization, Novel Coronavirus (2019-nCoV) Situation Report – 22, 2020Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, et al., Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol . 2020;77;1–9.Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, et al., Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med . 2020;382;2268-2270.Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol . 2020;92;699-702.Bulfamante G, Chiumello D, Canevini MP, Priori A, Mazzanti M, Centanni S, Felisati G. First ultrastructural autoptic findings of SARS-Cov-2 in olfactory pathways and brainstem. Minerva Anestesiol . 2020.Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, Ueno M, et al., A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis . 2020;94;55-58.Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci . 2020;11;995-998.Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science . 2020;367;1444-1448.Yamagata R, Nemoto W, Nakagawasai O, Takahashi K, Tan-No K. Downregulation of spinal angiotensin converting enzyme 2 is involved in neuropathic pain associated with type 2 diabetes mellitus in mice.Biochem Pharmacol . 2020;174;113825.Mukerjee S, Gao H, Xu J, Sato R, Zsombok A, Lazartigues E. ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons.Hypertension. 2020;74;1181-1191.Kehoe PG, Al Mulhim N, Zetterberg H, Blennow K, Miners JS. Cerebrospinal Fluid Changes in the Renin-Angiotensin System in Alzheimer’s Disease. J Alzheimers Dis. 2019;72(2):525-535.Cairns DM, Rouleau N, Parker RN, Walsh KG, Gehrke L, Kaplan DL. A 3D human brain-like tissue model of herpes-induced Alzheimer’s disease.Sci Adv. 2020;6;eaay8828.. Flores G, Flores-Gómez GD, Gomez-Villalobos MJ. Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia. Synapse. 2016;70;198-205.Dalakas MC. Guillain-Barré syndrome: The first documented COVID-19-triggered autoimmune neurologic disease: More to come with myositis in the offing. Neurol Neuroimmunol Neuroinflamm . 2020;7; e781.Faucher A, Rey PA, Aguadisch E, Degos B.Isolated post SARS-CoV-2 diplopia. J Neurol. 2020;1–2.Joob B, Wiwanitkit V. COVID-19 and Guillain-Barré syndrome. Rev Neurol (Paris), 2020.Wang L, Shen Y, Li M, Chuang H, Ye Y, Zhao H, Wang H. Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. J Neurol . 2020;1–13.Asadi-Pooya AA, Simani L Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci . 413,116832..Kanwar D, Baig AM, Wasay M. Neurological manifestations of COVID-19. J Pak Med Assoc. 2020;70(Suppl 3), S101-S103.Kosugi EM, Lavinsky J, Romano FR, Fornazieri MA, Luz-Matsumoto GR, Lessa MM, Piltcher O, Sant’Anna GD. Incomplete and late recovery of sudden olfactory dysfunction in COVID-19. Braz J Otorhinolaryngol , 2020;S1808-8694, 30059-30068.Baig, A.M. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther . 2020;26;499-501.Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic Alterations Due to Respiratory Virus Infections. Front Cell Neurosci . 2018;12;386.Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients.J Med Virol . 2020;92;552-555.Guyenet PG, Bayliss DA. Neural Control of Breathing and CO2 Homeostasis. Neuron. 2015;87;946-961.

IntroductionHuman cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that persistently infects the majority of the human population worldwide (Cannon et al., 2010). Following primary infection under the control of a healthy immune system, a latent infection is established that persists lifelong (Reeves et al., 2005). Although primary infection is mostly asymptomatic in healthy individuals, HCMV may lead to significant morbidity or mortality in immunocompromised patients, particularly transplant recipients and AIDS patients (Griffiths et al., 2015). Vertical transmission of HCMV is a leading cause of congenital infection, resulting in deafness and intellectual disability in newborns (Manicklal et al., 2013). Existing therapies that either target the viral polymerase or terminase are associated with significant toxicity and/or sporadic resistance (El Helou and Razonable, 2019). The identification and characterisation of critical facets of host innate immunity that are targeted for degradation by HCMV proteins thus has important implications for antiviral therapy, since such interactions may be inhibitable by small-molecules, facilitating endogenous inhibition of viral replication (Nathans et al., 2008).HCMV has been reported to disrupt interferon (IFN) production, neutralise the IFN response (Le-Trilling and Trilling, 2015;Goodwin et al., 2018), inhibit natural killer (NK) cell activation (Patel et al., 2018), and avoid T cell surveillance via downregulation of MHC molecules (Jackson et al., 2011). A common final pathway for many host protein targets is proteasomal or lysosomal degradation (Halenius et al., 2015). For example, HCMV facilitates viral replication by degrading components of cellular promyelocytic leukemia nuclear bodies (PML-NB) Sp100, MORC3 and DAXX that act as restriction factors (Kim et al., 2011;Tavalai et al., 2011;Schreiner and Wodrich, 2013;Sloan et al., 2016).We previously developed three orthogonal proteomic/transcriptomic screens to quantify protein degradation early during HCMV infection, identifying 133 degraded proteins that were enriched in antiviral restriction factors. The power of this approach was demonstrated by our identification of helicase-like transcription factor (HLTF) as a novel restriction factor that potently inhibited early viral gene expression and was targeted by the HCMV protein UL145 (Nightingale et al., 2018). However, a global approach to identify the mechanism of HCMV-induced protein degradation is lacking. Our previous study employed the broad, non-selective inhibitor MG132, which is known to affect lysosomal cathepsins in addition to the proteasome (Wiertz et al., 1996), and leupeptin which is a naturally occurring protease inhibitor that can inhibit some proteasomal proteases in addition to the lysosome (Nightingale et al., 2018).In this study, we used the selective proteasome inhibitor bortezomib (Chen et al., 2011) to identify proteins specifically targeted for proteasomal degradation during HCMV infection. This identified that the majority of proteins rescued from degradation by MG132 were also rescued by bortezomib, highlighting the role of viral subversion of the proteasome in immune evasion. Our data additionally provide a shortlist of proteins degraded by the proteasome early during infection that are enriched in known antiviral factors for further investigation.

SARS-COV2 virus is originated from a closely related  bat Coronavirus RaTG13 after gaining insertions by exchanged recombination with  pangolin virus Pan_SL_COV_GD. SARS-COV2 uses its entry-point key residues in S1  protein to attach with ACE2 receptor to infect human. The evolution of  SARS-COV2 could include any of these three possibilities: it entered human from  bat early with its poorly developed entry-point residues and remained silent  for long time with slower mutation rate to evade human immune system but  eventually perfected them for widespread infectivity; or recently with  efficiently developed entry-point residues having more infective power but  adapted  with higher mutation rate to  evade human immune system; or recently through an intermediate host having  human like conditions where it mutated both its entry-point residues as well as  immune evading system to survive easily in human. RaTG13 shows 96.3% identity  with SARS-COV2 genome of 29903 base implying that it substituted ~1106  nucleotides to become present-day virus. Using pairwise sequence analysis of  eighty-three SARS-COV2 genome from December, 2019, we show that its mutation  rate in human is as low as 36 nucleotides per year that would take  approximately 30 years to emerge as SARS-COV2 from bat RaTG13. Furthermore, a  critical entry-point residue 493Q that binds with K31 residue of ACE2  is evoluted from RaTG13 amino acid Y, which  needs the code must be mutated twice with an intermediate virus carrying amino  acid H (Y>H>Q). However, such an intermediate COV virus with 493H has not  been identified in bat or pangolin. Taken together, absence of any evidence of  silent presence of SARS-COV2  in human for  a long time or very high  mutation rate  or  an intermediate host or virus  emphasizes that either such an intermediate host or virus must be still obscure  in nature  or the emergence of SARS-COV2 is  urguably doubtful. 

Introduction: Respiratory Syncytial Virus (RSV) is the main causative agent of respiratory tract infections at pediatric ages in Mexico and around the world. In our study we determine and correlating clinics characteristics to the levels of specific IgA against RSV in respiratory samples for infected children and the absence or presence of exclusive breastfeeding. Material and methods: This is a clinical, ambispective and comparative study. There were included all patients pediatrics hospitalized and the samples of nasopharyngeal exudate were obtained, there was performed an ELISA on them with a Human Respiratory Syncytial Virus to determine the levels of specific IgA against RSV. Results: The total of patients included was 197. Finding that only 4.1% of infants received a complete vaccination schedule. Up to 22.8% were coinfected with a virus upon admission. There was found a significant difference in the rate of oxygenation during the admission presented by lactated vs non-lactated patients (p 0.002), as well as the presence of crackles p = 0.029 (95% CI 0.502-0.095) and wheezing p = 0.043 (95% CI 0.522-0.980), and a difference between the levels of specific IgA and the personal history of repeated respiratory tract infections (p = 0.018). Differences in symptoms such as dry cough, thoracoabdominal dissociation (p = 0.043, p = 0.044 respectively), were found as well. Conclusions: The results obtained from this research lead to stablish that low levels of specific IgA against RSV in the airways, are statistically and clinically related to greater severity of RSV infection.

The research on the structure-function relationship between the molecular flexibility and emulsifying properties of soybean protein isolate (SPI) under Maillard reaction conditions is still very limited until now. This paper investigated the effects of different pH values (5.0, 6.0, 7.0, 8.0, 9.0) on the molecular flexibility, emulsifying activity and emulsion stability of Maillard reaction products between soybean protein isolate with glucose. As the pH increased, the degree of grafting and browning of soybean protein isolate-glucose (SPI-G) increased significantly. The results of secondary structure analysis showed that the α-helix content decreased, which further proved that the protein flexibility increased. Correlation analysis showed that there was a good correlation between molecular flexibility and emulsifying properties of SPI-G. The correlation coefficient between the molecular flexibility and emulsifying activity of SPI-G was 0.963 (P <0.01), and the correlation coefficient between the molecular flexibility and emulsion stability of SPI-G was 0.879 (P <0.05).

Oil flow with different particles was tested in a square tube using PIV measurement technology. The instantaneous velocity vector data of the flow field were acquired in oil with different particle sizes and concentrations of the particles, and the distributions of the transient speed and average speed and the pulsation intensity of oil along the streamwise and wall-normal directions were analyzed. The results showed that the distribution of the streamwise pulsation intensity of oil changes more gently along the wall-normal direction in the center region and changes more steeply in the near-wall area. With increasing particle concentration, the streamwise pulsation intensity of oil decreases gradually. The distribution of the wall-normal pulsation intensity of oil along the wall-normal direction is roughly “w”-shaped under different particle grain diameters. The amplitude value of the wall-normal pulsation intensity of oil is larger in the center region and near-wall area, and the effect of the particle concentration in oil on the distribution of the wall-normal pulsation intensity of oil is not unidirectional. With increasing particle concentration, the main frequency trend of the oil speed along the streamwise and wall-normal directions decreases, and the streamwise average speed of the oil increases. The change in the wall-normal average speed of oil decreases when the particle concentration is under 3.00 ppm, and the normal velocity of oil increases when the particle concentration is over 3.00 ppm

Objective: To assess the cost-effectiveness of induction of labour (IOL) with outpatient balloon catheter cervical priming versus inpatient prostaglandin (PG) vaginal gel or tape. Design: Economic evaluation alongside a multi-centre, randomized controlled trial. Setting: Eight Australian maternity hospitals. Population: A total of n=448 women with a live singleton pregnancy, cephalic presentation, at or beyond 37+0 weeks gestation, undergoing IOL for low-risk indications between September 2015 and October 2018. Methods: An economic decision tree model was designed from a health services perspective. Sensitivity and subgroup analyses were performed to test the robustness of model outcomes. Main Outcome Measures: We estimated resource use from time of IOL to discharge of mother and infant, collected data on health outcomes (using EQ-5D-3L questionnaire) and reported cost per quality-adjusted life year (QALY) gained, incremental cost-effect ratio (ICER) and net monetary benefit (NMB). Results: Deterministic analysis showed lower mean costs (AUD $7,294 versus AUD $7,585) in the outpatient-balloon (n=205) compared to the inpatient-PG group (n=243), with better health outcomes (0.75 vs 0.74 QALYs gained) and overall higher NMB ($30,054 vs $29,338). In probabilistic analyses outpatient-balloon IOL was cost-effective in 55.3% of all simulations and 59.1% for women with favourable cervix (modified Bishop score >3) and 64.5% for nulliparous women. Conclusions: Outpatient-balloon IOL might be cost-saving compared to inpatient IOL with PG and is most likely to be cost-effective for nulliparous women. Funding: There was no external funding source for this study. Keywords: Decision analysis, labor induced, cost-effectiveness, prostaglandin, balloon ripening, randomised controlled trial

Background: Left ventricular hypertrophy is associated with poor prognosis and ad-verse events. Left ventricular and left atrial global strain and left atrial reservoir strain (LV-GS; LA-GS; LA-RS) could be used as markers for myocardial function in different forms of ventricular remodeling. The aim of this study was to evaluate LV-GS and LA-GS scores in different ventricular remodeling variants and identify risk factors for myo-cardial dysfunction. Methods and Results: This cross-sectional study was divided into four groups of ventricular remodeling: normal geometry, eccentric hypertrophy (EH), concentric hypertrophy (CH) and concentric remodeling (CR). Strain analysis was obtained using standardized protocols. We included 121 subjects, 33 with previous myocardial infarction (MI). We found that EH had the lowest LV-GS and CH the lowest LA-GS and LA-RS. Atrial and ventricular dysfunction was present in 40 (33%) and 14 (11.5%) subjects, respectively. Smoking, male sex and previous MI were associated with LV dysfunction and smoking and dyslipidemia with LA dysfunction. EH was closely associated with LV dysfunction and CH with LA dysfunction. Conclusions: We conclude that different types of ventricular geometry had echocardiographic profiles associated with different risk factors for dysfunction assessed by strain. The assessment of ventricular remodeling by global strain could be used as a complementary tool in the echocardiographic evaluation of ventricular and atrial function.

The emergence and outbreak of coronavirus disease 2019 (COVID-19) poses great challenges to our society, economy, and public health, and has already become an international public health emergency. The prevention and control of COVID-19 requires early detection and the timely and effective control of virus dissemination. Front-line medical personnel in the outpatient and emergency departments of hospitals, quarantine centers, and entry and exit ports are key to the early detection and control of COVID-19. Based on experiences in the prevention and control of other new and recurrent infectious diseases, epidemiologists previously proposed the concept of “vital sign zero” and the “Identify-Isolate-Inform” (3I) system for the detection and control of infectious diseases. The use of “vital sign zero” and the “3I system” for COVID-19 will facilitate the prevention and control of new infections, provide more timely treatment and effective isolation of patients, and protect the safety and health of medical workers. These concepts will also prevent the spread of COVID-19 and help to ensure public health and safety.

Background: Some long QT syndrome (LQTS) patients experience breakthrough cardiac events (BCEs) despite maximal therapy. Small studies have shown that intentional permanent atrial pacing (IPAP) is beneficial in refractory LQTS. As such, we sought to determine the genotype-specific utilization and efficacy of IPAP in a single-center LQTS registry. Methods and Results: In this retrospective study, electronic medical records from 1,065 LQTS patients were used to identify individuals that received IPAP. Pre- and post-IPAP heart rate, heart rate-corrected QT (QTc) values, annual BCE rate, and IPAP-related complications were compared between genotypes. BCEs were defined as LQTS-associated syncope/seizures, ventricular arrhythmia (VA)-terminating ICD therapies, and sudden cardiac arrest/death. Overall, 52/1065 LQTS patients received adjunctive IPAP therapy [77% female; median age 18.5 (IQR 1-35.5) years; 73% with prior VA]. Over an average IPAP follow-up of 121  82 months, the average heart rate increased from 65.8  20.4 bpm to 78.9  17.1 bpm; (p<0.01) and the average QTc decreased from 533.4  66.6 ms to 488.3  52.4 ms; (p<0.01). The mean BCE rate dropped from 0.88 to 0.19 per patient-year (p=0.01), driven by a marked decrease in LQT2 patients (1.01 BCE/year to 0.02 BCE/year; p=0.003). No serious IPAP-related complications were observed. Conclusion: In high-risk LQTS patients, namely those with recalcitrant LQT2, IPAP appears to be a safe and efficacious adjunct therapy. The beneficial effects of IPAP may stem from attenuating the QTc and circumventing a pause-dependent trigger. Whether IPAP might obviate the need for an ICD in some instances warrants further study.

Introduction: Cardiac autonomic system modulation by endocardial ablation targeting atrial ganglionated plexi (GP) is an alternative strategy in selected patients with severe functional bradyarrhythmias, although no consensus exists on the best ablation strategy. The aim of this study was to evaluate if a simplified approach by a purely anatomical guided ablation of just the atrial right GP is enough for the treatment of these patients. Methods: We prospectively enrolled patients with significant functional bradyarrhythmias and performed endocardial ablation purely guided by 3D electroanatomic mapping directed at the atrial right GP and accessed parameters of parasympathetic modulation and recurrence of bradyarrhythmias. Results: Thirteen patients enrolled (76.9% male, median age 51, 42-63 years). After ablation, a median RR interval shortening of 28.3 (25.6–40.3)% occurred (111, 937.5-1395.4ms to 722.9, 652.2-882.4ms, p=0.0015). The AH interval also shortened (19, 10.5–35.7%) significantly after the procedure (115, 105-122ms to 85, 71-105ms, p=0.002) as well as Wenckebach cycle length (11.1, 5.9–17.8% shortening) from 450, 440-510ms to 430, 400-460ms, p=0.0014. On 24-hour Holter monitoring there was significant increase in heart rates (HR) of patients after ablation (minimal HR increased from 34 (26-43)bpm to 49 (43–56)bpm, p=0,0063 and mean HR from 65 (47-72)bpm to 78 (67-87)bpm, p=0.0015). No patients had recurrence of symptoms or significant bradyarrhythmias during a median follow-up of 8.4 months. Conclusions: A purely anatomic guided procedure directed only at the atrial right ganglionated plexi seems to be enough as a therapeutic approach for cardiac parasympathetic modulation in selected patients with significant functional bradyarrhythmias.

Sir, We read with interests the article by Kate F Walker and colleagues, entitled ”Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis”. We would like to discuss some points that merit further.In the article, the authors systematically analyzed the mode of delivery on the infection rates of COVID-19 of newborn, they found that the infection rate is no greater when the baby is born vaginally, breastfed or allowed contact with the mother, compared with those performed with Caesarean sections.Despite the limitations, especially the retrospective feature, this study provided important information for the selection of mode of delivery with COVID-19, that Caesarean birth was not better than virginal delivery on neonatal infection outcomes.However, the main defect was the lacking severity evaluation of COVID-19 of the mothers, which may result in selective bias, or even alter the conclusion. Clinically, pregnant women combined with more severe degrees of COVID-19 always prefer Caesarean delivery than virginal delivery. Possibility was that the protective effects of Cesarean birth might have been neutralized by the severity of COVID-19.COVID-19 is a kind of highly contagious respiratory virus, Both the patients and doctors feel anxious about the possible increased infection risk during the second stage of the labor, for the virginal labor usually takes longer than Caesarean.Considering the above, prospective evaluation the safety of mode of delivery with COVID-19 would have important significance for clinical practice.Rui-hong Xue11Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Aims: Difficulties are often encountered while controlling atrial fibrillation (AF), especially in hemodialysis (HD) patients. Previous data revealed that cryoballoon ablation (CBA) for treating paroxysmal atrial fibrillation (PAF) was not inferior to radiofrequency ablation (RFA); however, HD patients were excluded in this prior trial. Thus, the efficacy of CBA for HD patients is still unknown. Methods: This retrospective study analyzed HD patients who underwent catheter ablation (CA) for AF from August 2011 to June 2019. Patients who received CBA (CBA group) and those who received RFA (RFA group) were compared. The primary endpoint was defined as freedom from a composite outcome (a documented recurrence of any atrial tachyarrhythmia or a prescription of antiarrhythmic drugs) at one year after CA. The secondary endpoint was freedom from a documented recurrence of any atrial tachyarrhythmia at one year after CA. Results: The RFA and CBA groups were composed of 21 and 23 patients, respectively. Freedom from a composite outcome was 58.4% in the RFA group and 68.2 % in the CBA group (Log-rank: p=0.571). Freedom from any atrial tachyarrhythmia was 63.5% in the RFA group and 90.9% in the CBA group (Log-rank: p=0.042). Conclusion: Our results suggest that patients on HD with AF who were treated with CBA tended to have better outcomes than patients treated with RFA. Therefore, CBA could be a suitable ablation method for HD patients.

Introduction: Randomized controlled trials (RCTs) have shown improved outcomes in patients undergoing first-line catheter ablation of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with ischemic cardiomyopathy (ICM). Herein, outcomes were stratified based on left ventricular ejection fraction (LVEF). Methods: RCTs evaluating first-line ablation versus medical therapy in patients with VT and ICM were included. Risk estimates and 95% confidence intervals (CI) were measured. Results: Four RCTs with a total of 505 patients (mean age 66 ± 9 years, 89% male, 80% with previous revascularization) were included. Mean LVEF was 35 ± 8%. At a mean follow-up of 24 ± 9 months, a significant benefit in survival-free from appropriate ICD therapies was observed in all patients undergoing first-line catheter ablation compared to medical management (RR 0.70, 95% CI 0.56-0.86). In patients with moderately depressed LVEF (>30-50%), first line VT ablation was associated with a statistically significant reduction in the composite endpoint of survival-free VT/VF and appropriate ICD therapies (HR: 0.52, 95% CI: 0.36-0.76), whereas there was no difference in patients with severely depressed LVEF (30-50%).