The COVID-19 pandemic has transformed lives across the world. In the UK there has been a public health driven policy of population ‘lockdown’ that had enormous personal and economic impact. We compare UK response/outcomes including excess deaths with European countries with similar levels of income/healthcare resources. We calibrate estimates of the economic costs as different %loss in GDP against possible benefits of avoiding life years lost, for different scenarios where local COVID-19 mortality/comorbidity rates were used to calculate the loss in life expectancy. We apply quality-adjusted life years (QALY) value of £30,000 (maximum under NICE guidelines). The implications for future lockdown easing policy in the UK are also evaluated. The spread of cases across European countries was extremely rapid. There was significant variation both in severity and timing of both implementation and subsequent reductions in social restrictions. There was less variation in the trajectory of mortality rates and excess deaths, which have fallen across all countries during May/June 2020. The average age at death and life expectancy loss for non-COVID-19 was 79.1 and 11.4years respectively while COVID-19 were 80.4 and 10.1years; including for life-shortening comorbidities and quality of life reduced this to 5QALY for each COVID-19 death. The lowest estimate for lockdown costs incurred was 50% higher than highest benefits from avoiding the worst mortality case scenario at full life expectancy tariff and in more realistic estimation they were over 50 times higher. Application to potential future scenarios showed in the best case a QALY value of £220k (7xNICE guideline) and in the worst-case £3.7m (125xNICE guideline) was needed to justify the continuation of the lockdown. The evidence suggests that the costs of continuing severe restrictions in the UK are so great relative to likely benefits in numbers of lives saved so that a substantial easing in restrictions is now warranted.

Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

Bird feathers serve multiple functions through their physical structure and coloration, but the evolution of functional novelty in bird feathers remains poorly understood. We investigated how selective pressures gave rise to seasonal coloration change in the feathers of the New World Warblers (Aves: Parulidae), a family with a remarkable diversity of plumage, molt, and life history strategies. Seasonal color changes in the plumages of migratory warblers are hypothesized to reflect a tradeoff between natural and sexual selection on the breeding and non-breeding distributions. We used comparative methods including phylogenetic path analysis to examine nested hypotheses relating to the evolution of seasonal dichromatism (i.e. breeding and nonbreeding plumages) and the molts that produce these plumages. We found that biannual molts likely evolved in response to increased feather wear and that changes in feather coloration evolved after the biannual molt itself. These results demonstrate that structural needs, not seasonal selection on coloration, drive the evolution of molt strategies in Parulidae. Importantly, once a biannual molt evolves, it served as a preadaptation for seasonal changes in plumage color. These results reveal how life history strategies act upon multiple and separate feather functions to drive the evolution of feather replacement patterns and bird coloration.

Objective: The research aimed to study the pregnancy outcomes and determine the safety of continued pregnancy until the third trimester after being infected with SARS-CoV-2 during early pregnancy. Design:Retrospective cohort study. Setting: Wuhan, Hubei, China.Population:Pregnant women in recovery who had a history of COVID-19 during early pregnancy at the Union Hospital from 15 Jan 2020 to 30 April 2020 were included. Methods:The clinical manifestation, laboratory examinations, treatment, pregnancy outcomes, maternal SARS-CoV-2 throat swab RT-PCR test results, and SARS-CoV-2 antibody tests in neonates were detected. The placental pathology, ACE2 expression and SARS-CoV-2 presence was also studied. Main outcome measures: Maternal and neonatal clinical and laboratory status. Results: We included cases in our study. Three cases were diagnosed with COVID-19 during early pregnancy (Case A to C), and two cases were serum IgG positive asymptomatic cases (Case D and E). Case A showed complete recovery after severe COVID-19. Case C was infected at 6 weeks during the first trimester and had induced medical abortion at 12 weeks. No pneumonia was found in all neonates, the nucleic acid test and serum IgM were negative, and IgG were positive. All placental samples were negative for SARS-CoV-2 nucleic acid test. Infants followed-up at 1-3 months were healthy and asymptomatic. Placental pathology showed chronic ischemia performance.Conclusions COVID-19 during pregnancy did not significantly affect pregnancy outcomes. No adverse outcomes were observed in all the neonates. The inflammatory state of COVID-19 may cause placental injury. The placenta does not appear be a target organ for SARS-CoV-2.

IntroductionThe coronavirus infected millions of people and caused a global pandemic. It was reported that the basic reproduction number R (0) of this infectious disease was 2.2, or even up to 6.6 [1-2]. About 20.9% of the confirmed diagnosis patients had no symptoms [3] that also made the new coronavirus more hidden and spread rapidly. For a while, the virus is rampant due to the strong infectivity and lack of effective antiviral drugs. Therefore it is urgent to develop effective drugs and vaccines. However, it will take quite a long time and huge efforts to develop vaccines and drugs that may miss the epidemic situation and the virus even may mutate. Chinese medicine that is symptom-oriented medicine was highlighted in this virus campaign in China by delaying the progress of the disease, reducing the sufferings of patients, and preventing the spread of the disease. There were clinical observations reported from Wuhan that integrated Chinese medicine and Western medicine could improve clinical symptoms two days faster than western medicine alone and cure fever in 2 days. And the improvement rate of CT image was 88.2%, the clinical cure rate was 94.1% and 5.9% of the general type progressed to the severe type, which were significantly better than those of the western medicine group (53.8%, 68.8%, 61.1%, 33.3%, respectively)[4]. Notably, the mortality rate of this clinical observation is only 2%, lower than that of the whole mortality rate in Wuhan area. This showed that the integration of Chinese and Western treatment could reduce the progress of novel coronavirus pneumonia (NCP), promote the recovery of severe and critical patients, and reduce mortality. In the future, more data reports on clinical research of TCM treatment are expected. From the perspective of modern medicine, it’s hard to make the complex mechanism clear since there are many components in Chinese herb remedies.Recently, many scholars have adopted modern methods to explore its action mechanism. However, there are many kinds of prescriptions actually used in clinical, which are individualized treatment according to the symptoms of patients rather than some fixed herbs. TCM recognizes diseases from the clinical manifestations of cold and hot symptoms of patients and chooses the prescription of anti-drug to treat. Simply, for example, the cold syndrome is treated by the herbs with warm or hot quality, the hot syndrome by the herbs with cold feature, and the damp syndrome treated by the herbs with dry character. We chose three kinds of clinically proven representative prescriptions according to the three different syndromes of the NCP. Then the Ma Huang decoction (cold syndrome), Yin Qiao powder (hot syndrome) and Da Yuan Yin decoction (damp syndrome) that were adopted in the treatment of NCP were selected. These three prescriptions are representative of the clinical experience of thousands of years in clinical application. To systematically elucidate the same disease treated with different herb prescriptions, we carried out the network pharmacological analysis to find out the universal biological mechanism behind the curative effect.

Fang and his colleagues have suggested to investigate the genetic predisposition for an increased risk of SARS-CoV-2 infection and they’ve proposed an explanation that might be linked to its receptor ACE2 polymorphisms1. The author agrees with their suggestion and would like to discuss it in a more elaborative manner.ACE2 polymorphisms and its induced mutations have been previously linked to enhanced susceptibility of heart diseases including coronary heart disease, myocardial infarction as have been revealed both clinically and experimentally2,3. Further, The ACE2 rs4646188 variant was suggested as a potential and optimal genetic susceptibility marker for essential hypertension, dyslipidemia and its related ischemic stroke4. Similarly, three ACE2 variants (rs4240157, rs4646155, and rs4830542) were found to be associated with essential hypertension and hypertension-related atrial fibrillation and left atrial remodeling5 Further, genetic variants in the ACE2 gene have been suggested to be associated with left ventricular mass, septal wall thickness and left ventricular hypertrophy in hemizygous men6. Noteworthy, genetic variants in the ACE2 gene were significantly associated with diastolic blood pressure responses to cold stress in the Chinese female population7. The author would like to suggest that It might be probable that ACE2 polymorphisms in the lungs could be one of the causes linked to a higher morbidity and/or mortality rate encountered in some groups of COVID-19 patients rather than the drugs suggested by Fang and his colleagues which have been refuted8. Further, these polymorphisms might also be one of the answers why some young, apparently healthy adults have been deceased while some very old patients have been rescued. The author recommends examining COVID-19 consented autopsies to explore this hypothesis as it might help us to develop some genetic tests to warn those more susceptible individuals exempt vulnerable health care professionals from duty.Conflict of interests:The author has no conflicts of interest to declare.Funding:None.References:1. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? The Lancet Respiratory Medicine 2020;8:e21.2. Wang W, Patel VB, Parajuli N, et al. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease. Journal of Molecular Medicine 2014;92:847-58.3. Yang W, Huang W, Su S, et al. Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population. Clin Sci (Lond) 2006;111:333-40.4. Pan Y, Wang T, Li Y, et al. Association of ACE2 polymorphisms with susceptibility to essential hypertension and dyslipidemia in Xinjiang, China. Lipids Health Dis 2018;17:241.5. Luo Y, Liu C, Guan T, et al. Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang. Hypertens Res 2019;42:681-9.6. Lieb W, Graf J, Gotz A, et al. Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy. J Mol Med (Berl) 2006;84:88-96.7. Huang J, Chen S, Lu X, et al. Polymorphisms of ACE2 are associated with blood pressure response to cold pressor test: the GenSalt study. Am J Hypertens 2012;25:937-42.8. ACEIs, ARBs, Ibuprofen linked to COVID-19: The other side of the broken mirror. 2020, June 2,. at https://www.authorea.com/users/318758/articles/456017-aceis-arbs-ibuprofen-linked-to-covid-19-the-other-side-of-the-broken-mirror?commit=c85d790e9c1c2a3e698675ed1798efe534abdfa7.)

1 IntroductionSpecies dispersal has a profound impact on species populations from ecological and evolutionary perspectives (Johnson & Gaines, 1990; Paradis et al., 1998), and represents the first stage of the invasion process (Davis, 2009). The causes of species dispersal are complex: it may be influenced by life-history, kin selection, avoiding of inbreeding depression, habitat loss, climate change, and species introductions (Clobert, 2012; Kokko, 2006; Travis & Dytham, 2002). Researching on species dispersal and distribution from the ecological niche perspective can help better understand biological responses to environmental changes (Ingenloff et al., 2017; McCauley et al., 2014). Otherwise, dispersal behavior into novel areas may pose challenges to the integrity of local ecosystems and biodiversity conservation (Tingley et al., 2014; Vilà et al., 2010). Therefore, it is necessary to study changing ecological niches and distribution trends during species dispersal.Over the past two decades, Ecological niche models (ENM) have been widely implemented in biological invasion research. Extensive research has revealed ecological niche dynamics, potential geographical distributions, driving factors behind invasion, and assessments of invasion risk using various modeling approaches, such as measuring niche characteristics and comparing differences between native and novel niches, analyzing habitat suitability, and predicting future spatial distribution trends (Beukema et al., 2018; Olivier Broennimann & Guisan, 2008; Mandle et al., 2010; Ørsted & Ørsted, 2019; Parravicini et al., 2015; Tingley et al., 2014; Villaverde et al., 2017). Studies of niche dynamics under climate change, which have received more attention, show the biological invasion often accompany with niche shift (O. Broennimann et al., 2007; Gallagher et al., 2010; Stiels et al., 2014). However, such conclusions can be suspicious because of insufficient evidence or inappropriate modeling frameworks, such as lack of analyses in environmental space, and excluding factors like partial niche filling, sampling bias, or the unequal availability of environmental conditions (Guisan et al., 2014; Peterson et al., 2011; Petitpierre et al., 2012; Qiao et al., 2017). Hence, an appropriate modeling method should be chosen rather than blind trust (Joppa et al., 2013; Qiao et al., 2015).On the other hand, the recent use of niche models for biological invasion-related studies on plants or animals have mainly focused on colonized species. For example, ring-necked parakeet (Psittacula krameri ) (Strubbe et al., 2015), brown marmorated stink bug (Halyomorpha halys ) (Zhu et al., 2017), and eastern gray squirrel (Sciurus carolinensis ) (Creley et al., 2019) are such studies. They emphasize the fundamental niche of the species. With the development of niche theory, the relevant niche concepts have been constantly improved (Guisan et al., 2014; Jackson & Overpeck, 2000; Peterson et al., 2011; Sax et al., 2013). In particular, Sax (2013) proposed the existence of a marginal zone outside of the fundamental niche, a ”tolerance niche” area in which individuals of a species can survive even if they do not currently have self-sustaining populations. Tolerance niches are prevalent among many species, especially those with dispersal and migration behaviors, such as the Amur falcon that breeds in east Asia and winters in Africa, so the winter niche is the tolerance niche. Combined with the stages of biological invasion (Davis, 2009), individual dispersal behavior before the establishment of a population in a new distribution area should also be included in the tolerance niche discussion. However, in contrast to colonized species, there is much less information about the niche dynamics mechanisms for species that have not yet successfully established in an invaded area (Bush et al., 2018; Feng & Papeş, 2017; Rosenblad et al., 2019). Here, we select a representative species with natural dispersal to investigate its niche dynamics and the potential effects of dispersal on the population.The Asian openbill (Anastomus oscitans ) is a large wading bird that specializes in forage mollusks. It belongs to the stork family Ciconiidae and is mainly distributed in South Asia and Southeast Asia, including India, Sri Lanka, Bangladesh, Myanmar, Thailand, Vietnam, and other countries (Elliott et al., 2020). Observed data in recent years describe a large-scale phenomenon of Asian openbill dispersal: the first was documented in Dali, China in 2006 (Wang, 2007), it was recorded by Perlis State in Chuping, Malay peninsula in 2008 (Lim et al., 2008), and it was first discovered in Singapore in 2013 (Low et al., 2013). The dispersal behavior can be divided into two directions: south to southern Thailand, Malaysia, Singapore and north to northern Vietnam and China, and the number of dispersed individuals has increased from a few to thousands each year (Han et al., 2016; Jiang, 2010; Liu et al., 2015; Low et al., 2013). Data showed that no breeding behavior was found in any population of Asian openbill in the new distribution areas (Han et al., 2016; Low et al., 2013; Zainul-Abidin et al., 2017), and presented that majority population are subadult birds and the population is more in summer and less in winter in China (Han et al., 2016; Lei et al., 2017). In comparison to temperate species, tropical species are generally adapted to a narrow and constant range of abiotic conditions (Gaston & Chown, 1999; Janzen, 1967), It is interesting when tropical birds naturally spread to both low and high latitudes, hence the following questions about abiotic conditions during Asia openbill dispersal: 1) Did the niche change during the dispersal process? 2) Is it possible to establish populations successfully in new areas? 3) Based on the present niche characteristics, how might the Asian openbill spread in the future?

1. Detritivores need to up-cycle their food to increase its nutritional value. One method is to fragment detritus promoting the colonisation of nutrient-rich microbes, which consumers then ingest. This is known as microbial gardening. Observations and numerical models of the detritus-dominated ocean mesopelagic zone have suggested microbial gardening by zooplankton is fundamental process in the ocean organic carbon cycle, as it leads to increased respiration of carbon-rich detritus. However, no experimental evidence exists to prove microbial respiration is higher on smaller, fragmented detrital particles. 2. Using aquaria-reared Antarctic krill faecal pellets we showed fragmentation increased microbial particulate organic carbon (POC) turnover by 70 %, but only on brown faecal pellets of low nutritional value. Microbial POC turnover on un-and fragmented green faecal pellets of higher nutritional value was equal. Thus we find particle size alone is not enough to determine microbial activity, and the nutritional value and age of the particle are important. 3. We estimate mesopelagic zooplankton can potentially increase the proportion of essential nutrients (e.g. unsaturated fatty acids) in their food by at least 11 %. In addition we propose ‘communal gardening’ may occur whereby other mesopelagic organisms consume the particle and microbes gardened by a neighbouring detritivore. 4. Increases in microbial turnover of detrital POC reduces the sink of organic carbon in the ocean. Thus microbial gardening should be represented in models forecasting the future carbon cycle. Model parameterisations will require further understanding of the energetic gains to zooplankton communities, how microbial gardening influences other sinking particles such as detrital aggregates, and the relative importance of biological (i.e. particle lability, size and age) vs. physical (i.e. temperature and oxygen) constraints on gardening.

We systematically investigate the binding nature of CB[7] towards 20 amino acids in both neutral (AAs) and protonated (AAs+) states by quantum chemistry methods. The result indicates molecular recognition process are enthalpy-driven. Among AAs, Arg and Asn shows the largest binding strength to CB[7], and for AAs+, Gln+ and Asn+ bind to CB[7] the strongest. The binding strength of protonated CB[7]/AA+ is much stronger than that of neutral CB[7]/AA counterpart, due to the introduction of ion-dipole interaction and the increase number and strength of hydrogen bonds. Energy decomposition analysis (EDA) indicates that electrostatic interactions play major roles in both CB[7]/AAs and CB[7]/AAs+ complexes. Moreover, we analyzed the dependence of binding strength on single AA volume and dipole moment. This study is benefit for providing valuable information in predicting the recognition sites for sequence-based peptide or protein by CB[7] and rationally designing synthetic host molecule for specific peptide or protein recognition.

Invasive species are of increasing concern to the local biodiversity and ecology as the magnitude of biological invasions is increasing globally. The genetic structures of newly established invasive populations may reveal insights towards the invasion processes, making population genetics an important tool for understanding current invasions. Here we study newly established populations (<10-20 years before first sampling) of the cosmopolitan alien ascidian Botryllus schlosseri in four Puget Sound (Washington, USA) marinas, using eight polymorphic microsatellites. Up to seven sampling sessions over a period of 19 years revealed populations with fluctuating allelic richness (AR=2.693-4.417) and gene diversity (He=0.362-0.589). The populations were well differentiated on spatial and temporal scales and subjected to moderate genetic drift (Fs’=0.027-0.071). The obtained significant heterozygote deficiencies, positive inbreeding coefficients (Fis) and population structure measures (Fst) revealed that no population was under the Hardy-Weinberg equilibrium. Comparing these parameters with those from two Californian sites (Moss Landing and Santa Cruz, 1200 km southerly; invaded by Botryllus during 1940’s) revealed a connection between Moss Landing and Puget Sound, while Santa Cruz remained isolated. On the US west coast scale, this study revealed no major difference in invasive population dynamics between recently and decade long established populations, except for fewer alleles and lower He. When comparing ten worldwide sites, only few microsatellite loci displayed strong regional differences. With globally the lowest numbers of alleles and lowest genetic indices, the Puget Sound Botryllus populations exhibit genetic characteristics of recently established populations, further emerging as one of the youngest B. schlosseri populations, worldwide.

To survive within complex environmental niches, including the human host, bacteria have evolved intricate inter-species communities driven by competition for limited nutrients, cooperation via complementary metabolic proficiencies, and establishment of homeostatic relationships with the host immune system. Such complex, interdependent relationships have hampered attempts to culture many bacterial strains in research settings, where standard readout of co-culture experiments are usually limited to the relative abundance of each species. Here, we utilize a microfluidic-based co-culture system to characterize dynamic interactions between multiple oral bacterial isolates. Using time-lapse imaging, we define species-specific effects on spatial community relationships during co-culture of Streptococcus species and Staphylococcus aureus with Actinomyces species. Co-culture of Streptococcus cristatus or S. salivarius in nanoliter compartments with Actinomyces graevenitzii revealed localized exclusion of Streptococcus and Staphylococcus from media immediately surrounding A. graevenitzii micro colonies. This community structure did not occur with S. mitis or S. oralis strains, or in co-cultures containing other Actinomycetaceae species such as S. odontolyticus or A. naeslundii. Moreover, fewer neutrophils were attracted to compartments containing both A. graevenitzii and Staphylococcus aureus than to equal number of either species alone, suggesting a possible survival benefit from the interaction.

Objective: This study is to describe surgical morphological types of the crista fenestra (CF) in relation to round window membrane (RWM) and to determine its impact on cochlear implant (CI) via the RW insertion. Materials and Methods: A series of 140 cases of CI which were performed in tertiary referral centers for CI with intra-operative video recording. Two senior CI surgeons reviewed these recordings for detection of morphological classification. Results: 125 cases (89.28%) showed the type (A) CF, which sub-classified to: Type A-1 in 93 cases (66.42%), type A-2 in 26 cases (18.57%) and type A-3 in 6 cases (4.28%) Type (B) CF was detected in 15 cases, which sub-classified to: Type B-1 in 11 cases (7.85%) and type B-2 in 4 cases (2.85%). Conclusion: In spite of large morphological diversity, Crist Fenestra can be classified into two main types. Most of them were no need for its removal whereas in a minority of the cases it hinders electrode insertion and needs drilling. KEYWORDS: Cochlear implant, round window membrane, Crista fenestra, drilling.

This paper examines land use patterns of rural households and the association with food production and income across three different zones of various forest proximity across a landscape gradient (remote, intermediate and on-road) in the Chittagong Hill Tracts region of Bangladesh. We conducted in-depth semi-structured surveys of households (175-300) and farm owners (30) to collect information on people’s perceptions of land use change, present land use patterns and contributions to food production and income. Our research found that more than half of the surveyed households experienced a decline in the land available for food production over the past 30 years. The land use patterns revealed decreasing crop lands (mainly swidden farms) and an increase in areas of planted trees. However, household use of the reduced crop land has not affected food production in the on-road zone, whereas the diversity of food sources has declined. People living in more remote areas used larger areas of crop (swidden farms) and fallow lands, fruit orchard and accessed natural forest lands that provide a diverse reservoir of food sources. The current land uses contribute to variations in annual household income, with remote dwelling people earning less to those living in the intermediate and on-road zones. In summary, this transition of land uses over three decades and changes in income and food availability cannot be generalised across the region because of zone specific differences. We recommend a broader and context-reliant landscape management approach in consideration of the diversity of forest and tree benefits.

The increasingly wide knowledge of the microbiota, as well as its continuous relation with several pathologies, favours the interest, discovery and classification of all the bacteria that are part of it. The isolation of strain P3519T is possible thanks to the application of new strategies such as culturomics and taxono-genomics. Strain Marseille-P3519T isolated from the fecal flora of a 25-year-old healthy French woman was a Gram-positive anaerobic bacterium, non-motile and non-spore-forming. The 16S rRNA gene sequence of Marseille-P3519 showed 98.57% of sequence similarity with Lactobacillus caviae MOZM2, the closest species, phylogenetically. Its genome had 2,237,367 bp with 45.42 mol% of G+C content. These findings support that strain Marseille-P3519 is a new member of the genus Lactobacillus for which the name Lactobacillus caccae sp. nov., is proposed.

A document by Levio Quinto. Click on the document to view its contents.

The COVID-19 pandemic has had a profound effect on the practice of clinical medicine. Tremendous resources have been poured into caring for patients infected with the virus necessitating a reduction in elective medical procedures. The extent to which physicians have modified their behavior in treating non-COVID-19 patients remains unclear. To address this question, we queried major cardiology vendors (Boston Scientific, Abbott and Biosense Webster) in the Philadelphia region to quantify arrhythmia ablation and cardiac device implantation volumes at 27 hospitals. We observed a significant, inverse correlation between regional COVID-19 cases and cardiac electrophysiologic procedures since the beginning of the US outbreak in late January. Furthermore, we observed that atrial fibrillation ablation and ICD implantation rates dropped more than VT ablation and device generator change rates did consistent with a shift away from elective medical procedures. These results can inform expected procedural volume load and planning once routine clinical practice resumes.

Food allergy is increasing in prevalence, affecting up to 10% of children in developed countries. Food allergy can significantly affect the quality of life and well-being of patients and their families; therefore, an accurate diagnosis is of extreme importance. Some food allergies can spontaneously resolve in 50-60% of cow’s milk and egg allergic, 20% of peanut allergic and 9% of tree nut allergic children by school age. For that reason, food allergic status should be monitored over time to determine when to reintroduce the food back into the child’s diet. The gold-standard to confirm the diagnosis and the resolution of food allergy is an oral food challenge; however, this involves a risk of causing an acute allergic reaction and requires clinical experience and resources to treat allergic reactions of any degree of severity. In the clinical setting, biomarkers have been used and validated to enable an accurate diagnosis when combined with the clinical history, deferring the oral food challenge, whenever possible. In this review, we cover the tools available to support the diagnosis of food allergies and to predict food allergy resolution over time. We review the latest evidence on different testing modalities and how effective they are in guiding clinical decision-making in practice. We also evaluate predictive test cut-offs for the more common food allergens to try and provide guidance on when challenges might be most successful in determining oral tolerance in children.

Multisystem inflammatory syndrome in children (MIS-C) during the COVID-19 pandemic raised a global alert from the Centers for Disease Control and Prevention’s Health Alert Network. The main manifestations of MIS-C in the setting of a severe inflammatory state include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes, and in some cases it progressed to multi-organ failure. The low percentage of children with asymptomatic cases compared with mild illness and moderate illness could be correlated with the rare cases of MIS-C. One potential explanation for the progression to severe MIS-C disease despite the presence of readily detectable anti-SARS-CoV-2 antibodies could be due to potential role of antibody-dependent enhancement (ADE). We reason that the incidence of the ADE phenomenon whereby the pathogen-specific antibodies can promote pathology should be considered in vaccine development against SARS-COV-2.

Background：With the improvement of radiofrequency catheter ablation technology, an increasing number of patients with atrial fibrillation (AF) choose it as the treatment option. However, the individual recurrence rate after ablation is difficult to accurately predict. Objective：This study aimed to develop and validate an effective prognostic nomogram for predicting long-term recurrence of patients with AF who underwent ablation. Methods: We conducted a retrospective single-center cohort study of 493 patients with AF from five wards in The First Affiliated Hospital of Soochow University from January 1, 2015 to December 31, 2019. Three quarters of patients(n=371) were randomly assigned to the training cohort, and the rest (n=122) were assigned to the validation cohort. Univariate and multivariate cox regression analysis was performed using R software version 3.6.2 to prognostic variables for recurrence and develop a nomogram. The C index, ROC, calibration curve, Greenwood-D’Agostino-Nam, and DCA were used for verification in the modeling cohort and the verification cohort respectively for validation. Results: Multivariate cox regression analysis shown that 6 independent predictors were identified: age, female, AF duration, AF type, coronary artery disease, left atrial diameter. And these predictors were entered into the nomogram, which shown favorable discrimination and calibration both in the training cohort and validation cohort. Conclusion: The proposed nomogram can accurately predict recurrence of patients after AF ablation. Compared to the CHA2DS2-VASc score, clinicians can promote individual-oriented therapy and disease management by using this tool.

There is emerging evidence that a keen understanding of atrial myofiber architecture is paramount to characterizing and treating atrial arrhythmias. Heterogeneity in the three dimensional anatomic structure of the atrium has previously been shown to create distinct endocardial and epicardial activation patterns during tachycardia in a canine model (1). In the clinical setting, the epicardial atrial architecture and its contribution to arrhythmias have been less well explored until recently. There has been a renewed interest in and appreciation of epicardial and interatrial connections, particularly in the treatment of left atrial arrhythmias refractory to traditional endocardial ablation.The vein of Marshall has been postulated to harbor epicardial connections between the coronary sinus (CS) and the left atrium (LA), sustaining peri-mitral flutters refractory to endocardial ablation (2,3). Conduction across the intercaval bundle, which connects the right atrium to the right superior pulmonary vein, has been reported to render isolation of the RSPV challenging requiring ablation at the carina or from the RA (4,5). Similarly, the Bachmann bundle, the main pathway of interatrial connection, has been shown to be critical for maintenance of biatrial flutters (6,7). More recently, conduction across the subepicardial septopulmonary bundle has been implicated in the maintenance roof dependent flutter despite isolation of the endocardial posterior wall (8). In contrast, the role of epicardial connections in sustaining right atrial arrhythmias has been less well described.In this edition of the Journal, Chaumont et al. describe five patients who underwent electrophysiology study for typical atrial flutter, who had persistent arrhythmia despite achieving a line of block along the endocardial aspect of cavotricuspid isthmus (CTI) (9). Using entrainment and activation mapping during tachycardia, they identified atrial tissue critical to the arrhythmia circuit in the middle cardiac vein in four patients, and in close proximity to the CS ostium in one patient. Ablation at these locations restored sinus rhythm. Electroanatomic mapping was not available for most of these cases. Rather than a limitation, this absence allowed an amazing demonstration “old school” deductive electrophysiology.The authors should be commended for this series of cases which demonstrate connections that sustain atrial flutter by bypassing the endocardially blocked CTI. This study elucidates the complex, layered physiology underpinning atrial flutter, considered among the simpler of arrhythmias we treat in the electrophysiology laboratory. The strength of the study is the elegant intracardiac electrograms for each case which allowed the authors to infer the mechanism of refractory arrhythmia and eliminate it by targeting critical areas guided by EGMs within the coronary venous system. Prior studies of atrial fibrillation have suggested that epicardial-endocardial breakthrough maybe an important mechanism in maintenance of persistent AF (10). It appears that a similar mechanism maybe responsible for maintaining typical flutter refractory to endocardial CTI ablation.Based on their findings, the authors propose a CS to low right atrium (RA) epicardial connection in the first four patients, and an RA to RA epicardial connection in one patient critical to the tachycardia circuit. Anatomically, however, it is unclear whether discrete connections akin to accessory pathways exist between these regions of interest to explain the observed findings. It is more likely that the atrial flutter circuit encompasses the entire thickness of the atrium, and owing to fiber orientation across the two layers, there are regions where the endocardial and epicardial surfaces communicate with each other. At these locations we appreciate the epicardial component of persistent flutter once the endocardium is ablated and line of block is achieved but tachycardia continues uninterrupted. This concept is illustrated in Figure 1, which demonstrates a case of persistent mitral annular flutter refractory to endocardial mitral annular line. Epicardial conduction necessary for maintaining tachycardia was observed after endocardial ablation, and ablation from the coronary sinus slowed and terminated the tachycardia.The advent of high resolution 3-dimensional mapping systems has allowed characterization of atrial activation patterns in detail during tachycardia. Pathik et al investigated epicardial-endocardial breakthrough in activation mapping of right atrial macro-reentry tachycardia in 26 patients (11). They defined breakthrough as the presence of focal endocardial activation with radial spread unaccounted for by an endocardial wavefront, with same timing on every tachycardia cycle. Epicardial-endocardial breakthrough was observed in over 50% of the patients, with majority at the posterior RA, and one each at cavotricuspid isthmus postablation, RA septum, and the inferolateral RA. In four patients, areas of breakthrough were within the tachycardia circuit, and in one patient the breakthrough region was critical for arrhythmia maintenance. In all cases, breakthrough sites were adjacent to endocardial slowing or line of block—as mentioned above this finding is not entirely surprising, given that endocardial block is necessary to observe epicardial breakthrough while activation mapping.A detailed morphologic and histologic study of the inferior right atrial isthmus by Cabrera et al may provide some anatomical insight to explain the current study findings (12). The authors establish the isthmus to be an anatomically heterogeneous region, with the anterior aspect being consistently muscular, while the posterior membranous and the middle trabeculated aspects having variable ratios of muscle fibers to fibrofatty tissue, with myocardial bundles extending from terminal crest toward the Eustachian ridge to cover the mouth of the coronary sinus. In refractory atrial flutter following endocardial CT ablation, it maybe that ablation from the CS allows the elimination of residual conduction through these muscle fibers which is critical for maintenance of tachycardia.In conclusion, Chaumont et al should be congratulated for elegantly demonstrating the multi-layer physiological architecture of typical atrial flutter—a reflection of the anatomic complexity and heterogeneity of the cavotricuspid isthmus and its inputs, and of the atrial musculature in general. Appreciation of this complexity will undoubtedly empower us to characterize and treat this arrhythmia and others more effectively.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is a significant public health burden.1,2 Many mutations in ion-channel and non ion-channel structural genes are linked to AF especially in patients with family history and no risk factors.3 The pulmonary vein muscle sleeves are the main trigger for AF. 4 Many studies showed that pulmonary vein isolation (PVI) via catheter ablation is superior to medical therapy in decreasing all-cause mortality, hospitalizations and recurrence 5-7. Though it is still controversial, vagal denervation and targeting the major atrial ganglionated plexi (GP) have been reported by Pappone et al. to improve the outcome after PVI.8 GP ablation has been associated with QT prolongation and ventricular arrhythmias9. PVI affects the atrial GP, modifies the intrinsic cardiac autonomic nervous system and could lead to QT prolongation and lethal ventricular arrhythmias such as torsade de pointe and ventricular tachycardia.10In their study published in this issue of the Journal of Cardiovascular Electrophysiology, Chikata et. al investigated the effect of PVI on the QT interval in patients with paroxysmal AF, and identified associated predisposing factors . 11 This was a retrospective observational study of 117 patients (out of 280 patients who were screened) with paroxysmal AF who underwent PVI via cryoballoon, hotballoon and radiofrequency at Toyama Prefectural Center in Japan between January 2016 and June 2019. The authors assessed 12 lead electrocardiograms (ECGs) at baseline and after four hours, one day, one month and three months. At each evalulaion point, they included only patients with sinus rhythm and excluded those taking antiarrhythmic drugs, drugs known to prolong QT intervals, patients undergoing renal transplant or having electrolyte imbalances in order to eliminate possible confounding factors. They measured the QRS, heart rate, QT interval and calculated QTc using the Bazett, Fridericia, Framingham and Hodges formulas at each evaluation point. All patients underwent PVI under conscious sedation with the same anesthesia regimen. They performed Cavotricuspid isthmus line ablation only if the Cavotricuspid isthmus dependent atrial flutter was noted, and they did not perform any intentional GP ablation. The study showed that QTc interval calculated by Bazett formula and the Fridericia formula was significantly prolonged at each time point ,whereas that of the Framingham formula and the Hodges formula was significantly prolonged only in the acute phase. The authors attributed this discrepancy to how each formula correlates with heart rate (HR). Since PVI could lead to autonomic denervation, a reflex increase in heart rate can be expected especially during the acute phase following the procedure. Furthermore, the study showed that in the acute phase post PVI, women had significantly prolonged QTc interval as compared to their baseline and to men (P < 0.05).The authors explained that QTc calculated by the Bazzet formula is more prone to error especially at elevated heart rates seen post PVI. In the setting of tachycardia, the QTc can be expected to prolong since the R-R interval shortens to a greater extent than the QT. Hence, the Bazzet’s QTc formula will overcorrect and overestimate the prevalence of the QT interval at heart rate greater than 100 bpm, and linear regression methods to correct the QT interval (such as Hodges) are better for clinical use. Women are known to have a longer baseline QT interval and are more prone to develop torsade de pointe than men12. That could be explained by the hormonal effect on the expression of ion channels and by the difference in autonomic regulation between genders.13,14 Chikata at al show a possible association between gender and QT prolongation post PVI that might be explained by a difference in inflammatory response or a distinguished genetic predisposition found more frequently in women. Further investigation is warranted via prospective studies with larger sample size in the future to corroborate the findings especially with the relatively small sample size and the fact that it was a single center study.References:1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke . Aug 1991;22(8):983-8. doi:10.1161/01.str.22.8.9832. Chung MK, Refaat M, Shen WK, et al. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.3. Feghaly J, Zakka P, London B, MacRae CA, Refaat MM. Genetics of Atrial Fibrillation. Journal of the American Heart Association . Oct 16 2018;7(20):e009884. doi:10.1161/jaha.118.0098844. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. The New England journal of medicine. Sep 3 1998;339(10):659-66. doi:10.1056/nejm1998090333910035. Asad ZUA, Yousif A, Khan MS, Al-Khatib SM, Stavrakis S. Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Circulation Arrhythmia and electrophysiology . Sep 2019;12(9):e007414. doi:10.1161/circep.119.0074146. Refaat MM, Ballout J, Mansour M. Ablation of Atrial Fibrillation in Congenital Heart Disease. Arrhythm Electrophysiol Rev. Dec 2017; 6 (4): 191-4.7. Oral H, Knight BP, Tada H, et al. Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation . Mar 5 2002;105(9):1077-81. doi:10.1161/hc0902.1047128. Pappone C, Santinelli V, Manguso F, et al. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation . Jan 27 2004;109(3):327-34. doi:10.1161/01.cir.0000112641.16340.c79. He B, Lu Z, He W, et al. Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia. International journal of cardiology . Sep 20 2013;168(1):86-93. doi:10.1016/j.ijcard.2012.09.06710. Münkler P, Wutzler A, Attanasio P, et al. Ventricular Tachycardia (VT) Storm After Cryoballoon-Based Pulmonary Vein Isolation. The American journal of case reports . Sep 11 2018;19:1078-1082. doi:10.12659/ajcr.90899911. Chikata A. Prolongation of QT interval after pulmonary vein isolation for paroxysmal atrial fibrillation Journal of Cardiovascular Electrophysiology . 2020;12. Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation . Sep 15 1996;94(6):1471-4. doi:10.1161/01.cir.94.6.147113. Chen YJ, Lee SH, Hsieh MH, et al. Effects of 17beta-estradiol on tachycardia-induced changes of atrial refractoriness and cisapride-induced ventricular arrhythmia. J Cardiovasc Electrophysiol . Apr 1999;10(4):587-98. doi:10.1111/j.1540-8167.1999.tb00716.x14. Huikuri HV, Pikkujämsä SM, Airaksinen KE, et al. Sex-related differences in autonomic modulation of heart rate in middle-aged subjects. Circulation . Jul 15 1996;94(2):122-5. doi:10.1161/01.cir.94.2.122

During continuous very high gravity (VHG) fermentation, yeast cells exhibit sustained oscillation of residual glucose, ethanol, and biomass, which remains a fundamental and unanswered question associated with product inhibition. In this study, the oscillating process was characterized through transcriptome and metabolome analysis in one sinusoid cycle. By integrating analysis of 26 metabolites and 90 genes related to carbon metabolism, the results confirmed that fermentation oscillation could be attributed to intercellular metabolic oscillation with phase difference of sinusoidal waveform. Furthermore, expression changes of stress response genes indicated that dynamic ethanol inhibition was a primary factor responsible for the oscillation of metabolism. This study not only contributes to elucidation of the mechanism of oscillating fermentation through strong product inhibition, but also provides new understanding of other fermentation processes in an unsteady state.

A novel composite forward osmosis (FO) membrane was fabricated by introducing a chitosan (CS) sublayer between nanofibers and polyamide (PA) layer, which was beneficial to forming thin and defect-free PA layer and improved binding strength between substrate and selective layer. Results exhibited low reverse salt flux (0.73 gMH) while maintained high water flux (85.4 LMH), which were better than that in other reports. In order to further improve permeability of membranes, oxidized multiwall carbon nanotubes (OMWNTs) were added into PA layer based on the optimized sublayer. The crosslinking degree of PA layer was reduced, leading to loose PA layers, which promoted the increase of water flux. After modifying, water flux reached 96.9 LMH without sacrificing salt rejection. It was worth mentioning that PAN/CS composite FO membrane, which could adjust microstructure of support layer and selective layer respectively, may provide a promising way for preparing membranes with anticipated separation performance.

Background: It is common practice to observe patients during an overnight stay (ONS) following a catheter ablation procedure for the treatment of atrial fibrillation (AF). Objectives: To investigate the safety and economic impact of a same day discharge (SDD) protocol after cryoballoon ablation for treatment of AF in high-volume, geographically diverse US hospitals. Methods: We retrospectively reviewed 2,374 consecutive patients (1,119 SDD and 1,180 ONS) who underwent cryoballoon ablation for AF at three US centers. Baseline characteristics and longer-term safety were recorded during follow-up. The mean cost of an ONS was used to evaluate yearly cost savings as a function of the percentage of SDD cases/yearr. Results: There was no difference between SDD and ONS in the 30 day total complication rate [n=15 (1.26%) versus n=24 (2.03%); p=0.136 respectively]. The most common complication was hematoma in both the SDD (n=8; 0.67%) and ONS (n=11; 0.93%) cohorts. Sensitivity analysis demonstrated that when 50% of every 100 patients treated were discharged the same day, hospital cost savings ranged from $45,825 to $83,813 per year across US hospitals. Conclusions: SDD following cryoballoon ablation for AF appears to be safe and is associated with cost savings across different US hospitals.