In hemophilia A and B, analysis of the F8 and F9 variants has become standard over recent decades, giving information on the severity of hemophilia, inhibitor formation and allowing counseling for the families. The PedNet Registry collects data on hemophilia in children and has more than 2000 children listed. Genetic reports are collected uniformly and re-evaluated following international guidelines. We report 90 novel variants in the F8 and F9 gene, respectively, causing hemophilia with detailed information on severity, factor level and inhibitor formation. This will lead to further guidance for genetic laboratories and the treating physician. These findings can be implemented in hemophilia variant databases. The study highlights the need to re-evaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in the light of changed nomenclature, the use of in silico prediction and new sequencing techniques.

The complement system is a well-characterised cascade of extracellular serum proteins that is activated by pathogens and unwanted waste material. Products of activated complement signal to host cells via cell-surface receptors, illicting responses such as removal of the stimulus by phagocytosis. The complement system therefore functions as a warning system, resulting in removal of unwanted material. This review describes how extracellular activation of the complement system can also trigger autophagic responses within cells, upregulating protective homeostatic autophagy in response to perceived stress, but also intiating targeted anti-microbial autophagy in order to kill intracellular cyto-invasive pathogens. In particular, we will focus on recent discoveries that complement may also have roles in detection and autophagy-mediated disposal of unwanted materials within the intracellular environment. We therefore summarize the current evidence for complement involvement in autophagy, both by transducing signals across the cell membrane, as well as roles within the cellular environment.

IntroductionThe coronavirus disease 2019 (COVID-19) first outbreak at the end of 2019 in Wuhan, China, and quickly spread into more than 200 countries worldwide, turning into a global pandemic. As a new emerging and severe contagious disease, all people are vulnerable to it. Therefore, it’s not surprising that more and more pregnant patients are being reported.1, 2 The maternal and fetus outcomes of COVID-19 pregnant women are the focus of our attention. Fortunately, based on the results of current studies, the clinical characteristic and outcomes of COVID-19 maternal patients are similar to that of non-pregnant women. No maternal death has been reported.1, 2 But the consequences of infection with SARS-CoV-2 for fetus or newborn are uncertain; especially, there is still huge controversy regarding whether SARS-CoV-2 can be transplacentally transmitted from infected pregnant women to their fetuses. A previous review, through analyzing a total of 38 pregnant women with COVID-19 in China, didn’t found intrauterine transmission of SARS-CoV-2.2 However, a recent study by L Dong et al3 described a newborn born to a COVID-19 mother with elevated IgM antibody level to SARS-CoV-2, indicating a possible transplacental transmission.Here, we reported a newborn born to a convalescent COVID-19 mother has a viral pneumonia on the day of birth and elevated IgM/IgG antibody levels to SARS-CoV-2 at 3 days age.

Background : One of the highest causes of cardiac mortality is ST Elevation Myocardial Infarction (STEMI). Delay in the management of STEMI patients is a cause of high mortality and morbidity. A CODE STEMI program is established to help reduce door to balloon time and improve patient’s care and clinical outcome. Objectives : To determine the effect of the implementation of CODE STEMI program on Major Adverse Cardiac Event (MACE) and mortality of STEMI patients at Dr. Cipto Mangunkusumo General Hospital. Method: This is a retrospective cohort study that enrolled 207 STEMI patients who underwent primary percutaneous coronary intervention (PPCI) in 2015-2018. The patients were divided into two groups. The first group was treated prior to establishing the CODE STEMI program. The other group was treated according to the program, which was implemented in January 2017. Data were collected from medical records and we retrospectively analysed all in-hours, MACE, and mortality of STEMI patients from both groups. Data analysis was done using Mann Whitney and Chi square test. Results: There were 72 and 135 patients in Pre‐CODE STEMI and CODE STEMI groups respectively. D2BT was significantly reduced by 130 min (288±306 vs 158±81, P< 0.001)  since the implementation of CODE STEMI program. There were trends to lower in-hospital mortality rates (8.3% vs 4.4%, RR = 0.53) and MACE at 30 days (48.61% vs 37.78%, RR = 0.77). Conclusion: Implementation of CODE STEMI program can decrease the risk of MACE and mortality in STEMI patients in general hospital.

Accurate risk forecasting of agricultural water shortage has important meaning for the prevention and reduction of disasters in regional agricultural production. The encounter situation of effective precipitation (Pe) and crop water requirements (ETc) can determine the regional agricultural water shortage risk under natural precipitation supply condition. The Guanzhong Plain (GP), divided into Eastern Guanzhong Plain (EGP) and Western Guanzhong Plain (WGP), is sensitive to water shortage as a result of the local arid and semi-arid climate. Based on the daily meteorological data at six representative weather stations in GP from 1962 to 2016, Pe and ETc, which were marked as Pey, Pew, Pes and ETcy, ETcw, ETcs over a hydrological year, winter wheat growth period and summer maize growth period respectively, were computed and their marginal distributions were examined. Also, the copula functions were employed to model the joint distribution of Pe and ETc. The results indicated that the optimal fitted marginal distributions for Pey, Pew and Pes proved to be Lognormal, GEV and Normal in EGP, respectively, and Gamma, Log-Gamma and Weibull in WGP, respectively. GEV correlated all the ETcy, ETcw and ETcs optimally both in EGP and WGP. The Frank copula was identified as the most suitable model for the joint modelling of Pe and ETc series. According to the joint probability distribution, the asynchronous encounter probability of Pe and ETc was around three or four folds of the synchronous encounter probability in GP. Further, probabilities of the occurrence of slight, moderate, severe, and extreme agricultural water shortage under natural precipitation supply condition were 0.51, 0.20-0.30, 0.04-0.10, 0.01 in EGP, respectively, while the corresponding values were 0.52, 0.20-0.23, 0.03-0.09, 0.01 in WGP, respectively. Overall, GP confronted serious agricultural water shortage, and such incompatibility was more serious in EGP compared with WGP. This study can provide an important guidance for the adjustment of crop planting structure, the establishment of irrigation system and the optimal allocation of regional water resources.

This work aimed to test innovations for the diagnosis of agricultural properties at Rio do Peixe Watershed, to locate erosions and to correct them by changing soil management, aiming at recovering degraded areas, rehabilitating them and promoting conservation agriculture, evaluating the results by remote sensing and water quality indicators. In 2019, it turned twelve years of inspection/monitoring at Rio do Peixe Watershed. From 2007 to 2017, using the Conventional CDA methodology, 14,076 ha were inspected at Vera Cruz sector, 94 properties were notified and in Ocauçu, 82 properties, located in 9,027 ha. As a work strategy, in Marília, the Innovative CDA Methodology was used, which allowed the inspection and rehabilitation of 52 properties in 27,775 ha, from 2017 to 2018. After the notifications, the owners presented the conservationist technical projects for each property, which were implemented, using conservation practices such as improving vegetation cover and crop rotation to control laminar erosion and agricultural terracing, divergent channels and containment basin to control gullies erosions. This work promoted a transformation from degrading agriculture to conservation agriculture, having degraded pastures transformed into an agricultural area, implementing the No-tillage system. Pastures were recovered by implementing the Integrated Crop-Livestock System; it was possible to increase the occupancy rate by 31% comparing to the original situation. This is a great work that benefits Watershed farmers, increasing productivity and consequently the profit, as well as for the local people improving the quality of water that supplies the region of Marília.

Land subsidence caused by groundwater overexploitation is a critical global problem. Spatial distribution of land subsidence is crucial for environmental management and land planning due to the sensitive nature of land-surface gradients. Given the nonlinear relationship of subsidence and long-term drawdown from groundwater exploitation, and the heterogeneity of the aquifer in the Choshui River alluvial fan, a developed spatial regression model can effectively estimate nonlinear and spatially varying subsidence. That is, the root-mean-square-errors (RMSEs) of annual subsidences are less or equal to 0.8 cm. Considering various data inputs in the Choshui River alluvial fan, the spatial regression model offers a robust method for estimating the spatial patterns of subsidence using drawdown as observations. Results show that the largest water-level cone of depression occurs in the distal fan area. Nonetheless, the calculated subsidence bowl closely approximates the observed one located much farther inland. Without requiring extensive calibration or an elaborate numerical groundwater flow and subsidence model, the model provides reasonable and detailed patterns using a spatially varying relationship between drawdown and resulting land subsidence. Results indicate that the spatial regression model reasonably estimates the spatial distribution of the skeletal storage coefficient in the aquifer system. The large coefficient that represents inelastic compaction occurs in the inland areas, whereas the small coefficient that represents elastic compaction occurs along the coastal area. Furthermore, this model is relevant for water policy or land subsidence regulation.

Most cell penetrating peptides (CPPs) are unstructured and susceptible to proteolytic degradation. One alternative is to incorporate D-chirality amino acids into unstructured CPPs to allow for enhanced uptake and intracellular stability. This work investigates CPP internalization using a series of time, concentration, temperature, and energy dependent studies, resulting in a three-fold increase in uptake and 50-fold increase in stability of D-chirality peptides over L-chirality counterparts. CPP internalization occurred via a combination of direct penetration and endocytosis, with a percentage of internalized CPP expelling from cells in a time-dependent manner. Mechanistic studies identified that cells exported the intact internalized D-chirality CPPs via an exocytosis independent pathway, analogous to a direct penetration method out of the cells. These findings highlight the potential of D-chirality CPPs as bio-vectors in therapeutic and biosensing applications, but also identify a new expulsion method suggesting a relationship between uptake kinetics, intracellular stability, and export kinetics

Numerical investigation of a steam methane reforming process was performed from point of view to understand the heat flows inside a catalyst particle. To verify the numerical results, a new method based on the thermal conductivity equation has been developed to determine the temperature distribution inside the catalyst particle. The CFD-model was realized via ANSYS Fluent. To model the steam methane reforming process, the industrial Ni-based catalyst with a spherical particle was chosen. The temperature contours inside the catalyst particle and hydrogen mole fraction in the reaction space was calculated both numerically and analytically. The results show the irregularity in the distribution of the temperature field inside the catalyst. In the direction of flow, a minimum catalyst temperature occurs. In this case, the temperature decrease inside the catalyst occurs unevenly. Also, the temperature change on the catalyst surface as a function of flow time was analyzed.

Viruses are non-living particles containing genetic information in the form of DNA or RNA. They are fascinating because they are not considered a form of life even though they evolve in the same way all living organisms do. Viruses are so-called obligate pathogens because they cannot multiply unless they infect and hijack the cellular machinery in living organisms. 

This paper reports on the results of research aimed to translate biometric 3D face recognition concepts and algorithms into the field of protein biophysics in order to precisely and rapidly classify morphological features of protein surfaces. Both human faces and protein surfaces are free-forms and some descriptors used in differential geometry can be used to describe them applying the principles of feature extraction developed for computer vision and pattern recognition. The first part of this study focused on building the protein dataset using a simulation tool and performing feature extraction using novel geometrical descriptors. The second part tested the method on two examples, first involved a classification of tubulin isotypes and the second compared tubulin with the FtSZ protein, which is its bacterial analogue. An additional test involved several unrelated proteins. Different classification methodologies have been used: a classic approach with a Support Vector Machine (SVM) classifier and an unsupervised learning with a k-means approach. The best result was obtained with SVM and the radial basis function (RBF) kernel. The results are significant and competitive with the state-of-the-art protein classification methods. This opens a new area for protein structure analysis.

This is research material under development. If used, it should be cited properly. Citations to  published papers is scanty and it should be fixed along the way. To account for water movements in a catchment or any other control volume, let us assume that we can record the movements of small group of water molecules, called parcels, inside the control volume (cv) and at its boundaries. We do some assumptions first: 

The ongoing wide spread of Covid-19, also referred to as 2019-nCoV or SARS-CoV-2, is undoubtedly one of the deadliest zoonotic diseases the whole world has grappled with. As of April 10, 2020, this disease has infected above 1.6 million people in over 200 countries worldwide, and claimed the lives of more than 96,000.1 Figure 1 shows the distribution of confirmed cases in the first 20 nations with the highest number of Covid-19 patients as of April 10, 2020, the least of which has over 9,000 cases.**Figure 1**With the increasing trend of daily new cases and daily death from the beginning of March to April 9, 2020, as displayed on Figure 2, it could be predicted that this fatal pandemic could last well beyond a year. According to the modeling completed by pandemic intelligence experts at the Imperial College, London, the 2019 novel coronavirus is likely to remain for another 12-18 months.2 Typically, past pandemics have lasted between one to three years.3Examples of such recent pandemics are the H1N1 influenza,4 SARS-CoV,5Ebola,6 and MERS-CoV,7 which all lasted for more than 12 months. As the emergence of these novel viruses keep increasing, how could biosafety and biosecurity measures guard against the introduction of the harmful causative organisms to humans in the future?**Figure 2**The terms biosafety and biosecurity are broadly used in diverse frameworks and refer not only to protection of humans and their surrounding environment against lethal biological agents, but also to global deactivation of arms of mass destruction.8 In the concept of biorisk management, these two terms refer to best practices that prevent the spillover of toxic organisms to human beings and into the environment.9,10 Although these two terms have been used interchangeably and often denoted with similar meanings, scientists have distinguished between the two concepts. According to Zaki,11 biosafety involves all the preventive measures undertaken to eradicate strains of pathogenic microorganisms and their potential toxins. On the other hand, biosecurity includes a set of preventive strategies intended to reduce the risk of transmission of infectious diseases in humans, crops, livestock, isolated pests and genetically modified organisms.12The World Health Organization (WHO) has classified disease-causing microorganisms into four different groups based on their principal characteristics, hazardous threat to individuals and the community, and their route of transmission.13,14 Table 1 presents the four different groups with their associated risk levels.**Table 1**Concluding from the descriptions for the various pathogenic organisms and their risk levels to individuals and the community in Table 1, the novel coronaviruses that cause Covid-19, SARS-CoV, MERS-CoV, and many other pandemic-causing pathogens, could be classified as risk level 4 pathogens. As spillover events keep occurring in recent years, and more of these high-risk emerging infectious diseases (EIDs) are likely to be introduced into the environment, it is necessary for the general public and stakeholders around the globe to institute biosafety and biosecurity measures in preventing the transmission of these biological toxins to mankind, livestock and their inhabitations. Among the core elements of the principles of biosafety measures and biosecurity strategies, the following are principal in guiding against EIDs:Effective regulations have to be put in place to avoid and manage intentional exposures to the sources and hosts of pathogenic organisms of medium to high risk levels. Strict observation of such policies around the world will minimize human activities that have caused several spillover events in the past.As the sources of novel pathogens have been identified in the past, it is necessary for scientists to inform the general public about the sources and hosts of such toxic organisms. Further research should also be targeted towards identifying these pathogens in animals and plants which are usually exposed to the environment. Such knowledge will help stakeholders and policymakers to notify the general public about the potential spillover events that are likely from contacts with identified sources and hosts of these pathogens.The risk assessment of pathogenic diseases of the past and a predicted assessment of likely EIDs in the future should be made available to the general public. Such awareness will inform the mass about the economic, social, and health impacts of these diseases. This will reinforce public adherence to policies and regulations which are instituted to limit contacts with pathogenic sources as people are aware of the potential losses to national and global economy, and the adverse effects on social life and health facilities.As health personnel, scientists, and leaders in various capacities often find themselves in the frontline during the emergence of epidemic and pandemic diseases, they need to be trained adequately to guarantee proper apprehension and execution of biosafety procedures to ensure the maintenance of a safe working environment for individuals and the wider community. This will ensure appropriate measures are taken to limit the spread of infections.Finally, routine upgrades are required to render instituted biosafety and biosecurity measures more effective and efficient in this ever-changing world. As the etiology and epidemiology of EIDs keep evolving, constant updates to safe practices in health centers around the world are required to adapt these practices to effectively manage the emerging diseases.As various country-based mitigation measures are being implemented around the world to contain and control the course of Covid-19,15 it is essential that the above biosafety and biosecurity measures are adopted and implemented to effectively manage the ongoing outbreak, and prevent future emerging infections.

Angiotensin converting enzyme 2 activation: a novel potential Covid-19 therapeutic strategyIn late December 2019, the Covid-19 epidemic, caused by a novel coronavirus SARS-CoV-2, emerged in Wuhan, Hubei province, China. This epidemic has a doubling period of 1.8 days, and there are concerns about its progression to pandemic scales due to its exponential rate of spread. No specific drugs or vaccines are currently available for the treatment and/or prevention of SARS-CoV-2 infection. Hence, there is an imperative need to search for a safe and effective therapeutic strategy for Covid-19 infected patients, especially the critically ill individuals.Angiotensin-converting enzyme 2 (ACE2) is a crucial component of the renin-angiotensin-system (RAS) axis because it converts Angiotensin II into angiotensin (1–7), which exerts an antifibrotic, antihypertrophic and vasodilatory effect. ACE2 is a membrane-bound aminopeptidase which has been reported to be a functional receptor for coronaviruses, including SARS-CoV and SARS-CoV-2. The first step of SARS-CoV-2 infection is binding of the spike protein of the virus to ACE2 which is widely distributed on the alveolar type II cells and capillary endothelium (Lu et al., 2020). It has been demonstrated that SARS-CoV downregulates ACE2 protein in mice, contributing to severe lung injury (Kuba et al., 2005). This suggests that augmented ACE2 activation may result in enhanced binding with SARS-CoV-2. Thus, increasing ACE2 activation may have a dual function to both neutralize the virus and rescue cellular ACE2 activity protecting the lung from damage.Diminazene (DIZE) is an antitripanosomal drug which has been shown to serve as an ACE2 activator and reduce bleomycin-induced pulmonary fibrosis (Shenoy, Qi, Gupta, Katovich & Raizada, 2012). In addition, it has been reported that activation of ACE2 by DIZE prevented asthma progression in rats by altering AKT, p38, NF-κB and other inflammatory markers. DIZE also halted the development and progression of experimentally induced pulmonary hypertension in rats, improved right ventricular function, and diminished proinflammatory cytokines effects that were accompanied with increased lung ACE2 activity. Given the reported safety of DIZE administration in humans (Hutchinson & Watson, 1962; Pepin & Milord, 1994) and the pressing need for Covid-19 therapeutic, in addition to the well-documented pharmacological effects of DIZE, clinical studies are warranted to elucidate the potential safety and efficacy of DIZE in Covid-19 infected patients.In conclusion, SARS-CoV-2 represents a global health challenge. Unfortunately, no specific therapeutic options are currently available. Thus, there is an imperative need for a safe and effective drug in order to put this pandemic to an end. DIZE has a reported acceptable safety profile. Moreover, DIZE increased lung ACE2 activity in different experimental models, an effect which conferred lung protection against various insults. Taking into consideration the reported effect of SARS-CoV-2 on pulmonary ACE2 activity, it could be suggested that DIZE administration could offer some therapeutic merit for SARS-CoV-2 infected patients. However, clinical studies are required to unravel the potential safety and efficacy of DIZE administration in Covid-19 infected patients.Competing interests The author declares no competing interests.

In the present investigation temperature dependence fatigue strength behaviour of Inconel 825 super alloys is investigated. Based on the experimental results different S-N models have been derived and suitable model for the prediction of fatigue strength have been proposed. An inverse power and exponential relation between fatigue strength and absolute temperature is demonstrated. The proposed models are used to predict the fatigue life using well known Palmgren-Miner rule. Based on high to low and low to high load steps test data sets under identical test conditions, Miner rule based statistical damage constant is stochastically modeled for fatigue life prediction at different level of probability and validated. The modeling process combines a probabilistic fatigue damage accumulation and a stress-life-temperature relation technique.

Streamline maternal health care provision to mitigate the risk for pregnant women under COVID-19 pandemicHong Jiang1, Mu Li2, Huijing Shi1*, Xu Qian11School of Public Health; Global Health Institute; National Health Commission Key Laboratory of Health Technology Assessment, Fudan University, Mailbox 175, No. 138 Yixueyuan Road, Shanghai 200032, China;2School of Public Health; China Studies Centre, Room 313, Edward Ford Building, University of Sydney, Sydney 2006, Australia*Corresponding author: Huijing Shi, hjshi@fudan.edu.cn, School of Public Health; Global Health Institute; NHC Key Laboratory of Health Technology Assessment, Fudan University, Mailbox 175, No. 138 Yixueyuan Road, Shanghai 200032, China;The novel Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan City China in early December 20191,2, and has rapidly spread across the world. The pandemic has strained health system3, which presents a huge challenge to maintain other essential health services, including maternal health care. As the first country to experience the COVID-19 outbreak, there are lessons could be learnt for establishing a better preparedness mechanism from a service delivery perspective to provide essential maternal health care and mitigate health risk for pregnancy women.First, all health facilities providing antenatal care should apply high standard of precaution to ensure pregnant women are not exposed to the COVID-19 transmission. This includes setting up a triage area to screen for COVID-19 symptoms and contact history with confirmed cases before pregnant women entering antenatal clinics. People with COVID-19 exposure history, suspected cases or COVID-19 patients should be separated from other pregnant women and placed in designated areas. This will also protect antenatal care providers. Appointment is required in advance for antenatal service to ensure adequate social distancing and manage the patient flow in health facilities.Second, as routine service provision might be disrupted, perinatal care availability and any changes to service provision should be disseminated widely, preferably through online platforms4. Women with low risk pregnancy may reduce the risk of contracting COVID-19 by reducing the number of antenatal visits. Women with pregnancy complications and other health conditions should contact their antenatal care provider to seek specific advice. Communication and counselling can be provided to pregnant and postnatal women online, including recognizing warning signs of going to hospital urgently. During movement restriction or self-isolation guidance of keeping healthy diet and physical activity, and mental health support are important for the well-being of pregnant women.Third, balancing the demands of emergency responding to COVID-19 and maintaining essential perinatal health service at national, provincial and local levels. Guidelines on conditions that require continuing antenatal care and those can be delayed should be developed5. Designated hospitals for treating pregnant women with COVID-19 should be enlisted to ensure they will receive appropriate care from a multi-disciplinary team6. At the provincial/regional level, health authorities should adapt to local context and develop uniformed perinatal operational guidelines across all local health facilities and monitor the equitable access to service and service quality. Local health facilities are responsible for disseminating service information via official channels, e.g. account on social media platforms such as WhatsApp, Facebook, and providing services following the provincial/regional operational guidelines.As the pandemic intensifies globally7,8, the experience and lessons of China on the response and streamline health system may help other counties to mitigate adverse impact of the pandemic on maternal and newborns.Disclosure of interestsWe declare no competing interests.

Lopinavir combined with ritonavir were reported to benefit the patients with SARS by reducing the viral loads. However, in the latest clinical trials, no benefit was observed with lopinavir-ritonavir treatment beyond standard care in patients with COVID-19. We comment here that this disappointed result of clinical trial might result from the low volume of the lung distribution of lopinavir. The major reasons were listed below: 1) The binding affinity of ACE2 with SARS-CoV-2 spike protein is ~10- to 20-fold higher than the binding affinity of ACE2 with SARS-CoV spike protein, indicating that SARS-CoV-2 can enter AT2 cells in lung much easier than SARS-CoV. Therefore, the viral loads of SARS-CoV-2 might be much higher than viral loads of SARS-CoV in the lung tissue. 2) The concentration of lopinavir in the lung tissue was 1.18 μg equiv/ml in rats. The low volume of the lung distribution of lopinavir might not be enough to inhibit the coronavirus replication due to the high viral loads in the lung tissue. 3) In contrast, the concentration of chloroquine in the lung tissue was much higher (30.76 ± 0.85 μg equiv/ml) in rats, which might lead to its clinical and virologic benefits in the treatment of COVID-19 patients. Together, we proposed here that anti-SARS-CoV-2 drug repurposing studies should pay more attentions to the lung tissue distribution of antiviral drugs. The efficacy of antiviral drugs might depend on their lung tissue distributions

Dear Editor,Although a worldwide phenomenon, severe acute respiratory syndrome (SARS)-coronavirus (Cov)-2 infection is apparently less severe in some parts of the world. However, some countries present a surprisingly low death toll (https://coronavirus.jhu.edu/map.html downloaded in March 22, 11:00 AM). Epidemiology is crucial to tackle this pandemic as well as the search for compounds to treat. Turmeric (Indian saphron), a much-appreciated spice has India is by far the greater producer, and consumer, together with Pakistan, Malaysia, Bangladesh, Sri Lanka, Taiwan, China, Burma (Myanmar), and Indonesia (http://www.fao.org/fileadmin/user_upload/inpho/docs/Post_Harvest_Compendium_-_Turmeric.pdf downloaded in March 21, 2020). Curcuma or curcuminoids isolated from Turmeric have long been reported to have anti-inflammatory and immunomodulatory activity. Due to its very low bioavailability, alternatives to improve turmeric absorption have been developed. That is not to say that edible consumption would be of no effect (Aggarwal, Gupta & Sung, 2003). A world coronavirus map reveals that countries in southeast Asia present very low numbers of SARS-Cov-2 infections. Although numbers of infected people may not be reliable, the death rate is hard to be hidden. We focused our list on the major turmeric consumers but Taiwan given the strict rules for isolation implemented there. As of March 26, the death covid-19 toll reported in Indonesia, Malaysia, India, Pakistan, Bangladesh, Sri Lanka, and Burma, that represent over one-quarter of the world population was 128, being 78, 23, 14, 8, 5, 0, 0, respectively. On the other hand, Iran, which was a greater consumer of Turmeric, has experienced a shortage of this product due to economic sanctions, and had 2,234 deaths in March 22 (https://economictimes.indiatimes.com/news/economy/foreign-trade/turmeric-exports-hit-by-us-sanctions-against-iran/articleshow/70446034.cms?from=mdr). Community isolation has been hard to be implemented in Iran, which probably has shortage of health facilities and supplies to face this epidemic. Faced with data from developing countries, the death coronavirus disease (covid)-19 toll from high curcumin consumers is apparently very low as compared to those from developed countries, some of them with severe rules restricting social activities and better health infrastructure to treat patients. Would this just be coincidental? There are claims that drugs acting in the angiotensin converting enzyme (ACE) pathway may worsen the clinical picture of patients affected by SARS-Cov-2 (https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19 downloaded in March 21, 2020). ACE blocking compounds may lead to upregulation of the ACE2 gene receptor expression. It follows that ACE2 receptors are used by SARS-Cov-2 as a cell entry. It has been previously shown that rats subjected to thioacetamide induced hepatotoxicity are protected by Curcumin administration, an effect that was associated with down-regulation of the ACE gene (Akinyemi et al., 2015). Further, rats subjected to induced systemic arterial hypertension were protected by pre-treatment with ginger and turmeric rhizome supplementation, that led to reduction in ACE activity (Fazal, Fatima, Shahid & Mahboob, 2015). Hence, it might well be that Curcumin, by down-regulating ACE gene expression, can be of help against covid-19 disease. Notwithstanding, previous reports have shown that curcumin presents both direct and indirect antiviral activity against the human immunodeficiency virus (HIV) by inhibiting virus replication or via blocking inflammatory pathways operating in the acquired immunodeficiency syndrome (Prasad & Tyagi, 2015). Hard times pose hard problems that demand urgent policies. Health authorities worldwide are struggling to decide which is best to prevent people from getting covid-19 infection and, when the disease unleashes, which attitudes to preserve lives. There are various compounds being tested against covid-19. Hydroxychloroquine, given the safety profile of this well-known immunomodulating compound used in rheumatology for prolonged periods, is being indicated pending robust data to document its efficacy, if any, on the basis that it may be a non-expensive life-saving strategy posing no additional harm to an already affected SARS-Cov-2 patient (Touret & de Lamballerie, 2020). Using the best rationale to look for evidence about the therapeutic effects of turmeric in COVID19, we can do an exercise on Hill’s causality criteria. The strength of the association is high, based on the incidence map, and has been a repeated pattern in many countries with similar consumption of turmeric. There is some consistency between epidemiological and laboratory findings given that Curcumin apparently down-regulates ACE2 gene receptor expression, a major pathway in covid-19 cell entry (see above). We cannot yet claim specificity or biological gradient (dose-response relationship). Temporality is guaranteed because the consumption of saffron has long been incorporated into the culture of those countries. Similarly, chloroquine appears to interfere with the terminal glycosylation of the ACE2 cell receptor (Touret & de Lamballerie, 2020). At this time, we do not believe a ginger tea or adding turmeric to our meal would be of any harm. If in vitro data prove curcumin to be effective, clinical studies could be then proposed.

Since December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2（SARS-CoV-2）has swept 200 countries and regions worldwide1 and has become a ”Public Health Emergency of International Concern” (PHEIC). Pregnant women are susceptible to COVID-19 due to the changes in their physiology and the adaptability of their immune system2. During the outbreak of COVID-19, prenatal examinations may be postponed, however, delivery cannot be delayed, and the delivery room should work as usual. During this period, it is particularly important to quickly identify high-risk groups and to provide appropriate protection for childbirth and the puerperium. In accord with experience in China (Guidelines for the Prevention and Control of New Coronavirus Infections in Medical Institutions issued by the National Health Commission ), we strongly recommend that during the outbreak of COVID-19, all medical institutions should conduct graded, staged, comprehensive and continuous training of all staff, based on the particular epidemic prevention and control needs of for of different positions, to constantly improve staff’s awareness of the prevention and control of COVID-19. To strengthen staff comprehension of the necessary precautions during a COVID-19 epidemic, an assessment method that combines theory with scenario testing should also be applied 3,4. At the same time, based on our experience of delivery room management, we recommend a delivery room processing flow (Fig.1) and graded protection 5 (Table 1) for pregnant women with different infection risks，as detailed below:(1) Primary screening of all women (First level protective equipment should be applied): Check the axillary temperature and the fetal heart rate, and enquire whether there is fever, respiratory symptoms (cough, chest tightness, etc.), gastrointestinal symptoms (vomiting, diarrhea, etc.) and other symptoms before allowing women to sit in the maternity waiting area. Ask whether there is increased risk of contact with a COVID-19 positive patient (fever of any family member within two weeks, a history of traveling to the epidemic area or contact with a suspected or confirmed patient). Any positive history of the above indicates ‘potential risk’ status.(2) Pregnant women with potential-risk and/or suspected infection merit further screening (Second level protective equipment should be applied): attending staff should immediately apply second or third level of protective equipment, screening tests (which include respiratory pathogens tests like adenovirus, respiratory syncytial virus, influenza A virus, influenza B virus and parainfluenza virus, Mycoplasma pneumoniae and Chlamydia pneumoniae, blood routine tests, and C-reactive protein) should be undertaken and the new coronavirus nucleic acid test for pregnant women with potential-risk/suspected infection should be performed. A chest CT scan with informed consent to observe the lungs should be performed if signs or symptoms provide any indication (inform the patients about the necessity of chest CT and ask them to cover their abdomen properly). Obstetric management should not be delayed by testing for COVID-19.(3) Delivery room management (for vaginal delivery): ① Pregnant women suspected to be COVID-19 positive should be immediately transferred to an isolated delivery room (avoiding contact with other patients) or negative pressure delivery room and be required to wear surgical mask6. Accompanying family must not be permitted. Patients should be managed by specific experienced senior medical specialists, and third level protective equipment must be applied to avoid cross-infection; ② pregnant women at potential risk of infection: Accompanying family should not be allowed. Patients are recommended to wear surgical masks6 and should be transferred to isolated delivery rooms, with management/supervision by specific experienced senior medical specialists. Second level protective equipment should be applied to prevent cross-infection, if availability of protective materials is adequate. ③ low-risk pregnant women (those without any history of epidemiological exposure or clinical symptoms) should be transferred to an ordinary delivery room for delivery (avoiding contact with other patients). Second level protective equipment should be applied. It is recommended that these women wear disposable medical masks 6. Only family members who have no history of epidemiological contact and clinical symptoms within the past 2 weeks are allowed to attend the childbirth, and accompanying family members are also required to wear disposable medical masks.As fetal compromise is relatively common in pregnancies complicated by COVID-19 infection, continuous electronic fetal monitoring in labor is recommended for all women suspected with COVID-19, following transfer to the appropriate delivery room.7We advocate attempts to deliver vaginally without undue obstetric intervention and recommend caution regarding procedures such as episiotomy and ventouse/forceps delivery. Currently, we do not recommend water deliveries for pregnant women with suspected infection. There is no evidence that epidural analgesia or spinal anesthesia is contraindicated, therefore, epidural analgesia should be recommended to pregnant women suspected of COVID-19 infection before or in early labor to minimize the need for general anesthesia in emergency situations7.(4) Emergency caesarean section treatment：Suspected COVID-19 infection is not an indication for cesarean section, unless the woman’s respiratory condition demands urgent delivery, or pregnant women have other indications. Multi-disciplinary consultation involving anaesthetists, neonatologists, obstetricians, and infectious disease physicians is required before deciding to deliver prematurely in cases of suspected infection, and if Caesarean section is indicated, the procedure should be performed in a negative pressure isolation operating room (third level protective equipment should be applied). The choice of anesthetic mode is determined by the anaesthetist, based on the patient’s respiratory function. For pregnant women with potential infection (potential-risk), their pregnancy can be terminated in the isolated operating room (second level protective equipment should be applied) if properly protected. First level protective equipment is recommended when performing cesarean section for pregnant women with low-risk infection.(5) Postpartum management: postpartum vital signs, uterine contractions, maternal mental health and other conditions of the mother should be monitored, and attention paid to the prevention of postpartum hemorrhage, thrombosis, etc. For pregnant women with suspected infection, the neonatologist should be notified at least half an hour before delivery to take appropriate measures to isolate the newborn. Delayed cord clamping is still recommended given a lack of evidence to the contrary, unless there are other contraindications7. 14 days of isolation for newborns is recommended8; there is currently no evidence to support the suspension of breastfeeding in pregnant women with suspected infection, indeed, we advocate breastfeeding, as the wider benefits outweigh the potential risks of transmission through breastmilk 7. Isolation and preventive measures should be undertaken if referral is needed 5. If there are no abnormal signs/symptoms within two hours after delivery, mothers with suspected infection can be transferred to an isolation ward for further observation; ‘potential-risk’ pregnant women can be transferred to the isolation ward (avoiding contact with other patients) and low-risk mothers managed according to conventional procedures. Pregnant woman with suspected or potential infection should undergo diagnostic testing immediately. If infection is confirmed, the corresponding management should follow the previous guidelines for dealing with confirmed cases of COVID-192.(6) After-delivery protection procedures: After the mother was transferred to the ward, routine cleaning should be undertaken. The surfaces of the equipment (including the obstetric table, ultrasound machine, and neonatal warm bed) in the isolation delivery room and the negative-pressure delivery room need to be wiped and disinfected immediately, preferably with 1000 mg/L chlorine-containing disinfectant; 75% ethanol can be used for the non-corrosion resistance instruments7,9. Spraying is not a recommended method of disinfecting the equipment as this can affect the components. Dedicated cleaning tools are required to avoid cross contamination. The inspection room should be disinfected with ultraviolet light, ≥60 min each time, once or twice a day, with at least 30 min ventilation after irradiation. The ultrasound probe should be protected with a dark cloth during the irradiation. The room should be vacated when ultraviolet lamps are used.(7) Medical waste disposal: Protective supplies used by medical personnel and all patient waste should be regarded as infectious medical waste, which requires double-layer sealing, clear labeling, and airtight transport 10. If testing of the placenta and/or amniotic fluid is required, strict sampling and sealing should be carried out to avoid contamination of the surface of the container and the spread of infection. The surface of the container should be disinfected before sample inspection to further avoid infection of any personnel.

INTRODUCTION: Most of avoidable defibrillator therapies can be reduced by evidence-based programming, but defining tachycardia configurations across all device manufacturers is not straightforward. The aims were to determine if a uniform programming of tachycardia zones, independently of the manufacturer, result in a lower rate of avoidable shocks in primary-prevention heart failure (HF) patients and also if programming high-rate or delayed therapies can have some benefit. METHODS AND RESULTS: Prospective cohort with historical controls. HF patients with a primary-prevention indication for a defibrillator were randomized to receive one of two new programming configurations (high-rate or delayed therapies). A historical cohort of patients with conventional programming was analyzed for comparison. The primary endpoint was any therapy [shock or anti-tachycardia pacing (ATP)]. Secondary endpoints were appropriate shocks, appropriate ATP, appropriate therapies, inappropriate shocks, syncope and death. 89 patients were assigned for new programming group [high rate (n=47) or delayed therapy (n=42)]. They were compared with 94 historical patients with conventional programming. During a mean follow-up of 20±7 months, the new programming was associated with a reduction of any therapy (HR = 0.265, 95% CI 0.121-0.577, p=0.001), even after adjustment. Aproppriate ATP and any shock were also reduced. Syncope did not occur. Sudden, cardiovascular and all-cause deaths were not different between the groups. In the new programming group, neither high-rate nor delayed programming were better than the other. CONCLUSIONS: In our study, programming tachycardia zones homogeneously across all manufacturers was possible and resulted in a lower rate of therapies, shocks and appropriate ATP.

COVID-19 is a disease which is sweeping the globe, often with devastating consequences. The more we understand, the more it appears that infection has a very wide clinical spectrum from totally asymptomatic to life threatening. Without widespread community testing it is impossible to ascertain true infection rates and develop strategies which reduce or prevent transmission without the need for on-going draconian measures such as complete national lockdown. These measures are mandatory at the time of writing, however widespread adoption of face masks has been shown to help prevent transmission of other respiratory pathogens, and also infections acquired by healthcare staff. Combining mass testing with a combination of social distancing and face mask use might offer a way forward until a mass COVID-19 vaccination programme can be established.

Soft tissue, bone, and teeth reconstruction is a challenge in patients with maxillary defects due to surgical resections. This article presents a 21-year-old male patient with a history of hemimaxillectomy . Secondary reconstruction was performed using buccal fat pad flap, free iliac crest bone graft, and dental implants

Measuring biological diversity is a crucial but difficult undertaking, as exemplified in oaks where complex morphological, ecological, biogeographic and genetic differentiation patterns collide with traditional taxonomy that measures biodiversity in number of species (or higher taxa). In this pilot study, we generated High-Throughput Sequencing (HTS) amplicon data of the intergenic spacer of the 5S nuclear ribosomal DNA cistron (5S-IGS) in oaks, using six mock samples that differ in geographic origin, species composition, and pool complexity. The potential of the marker for automated geno-taxonomy applications was assessed using a reference dataset of 1770 5S-IGS cloned sequences, covering the entire taxonomic breadth and distribution range of western Eurasian Quercus, and applying similarity (BLAST) and evolutionary approaches (ML trees and EPA). Both methods performed equally well, with correct identification of species in sections Ilex and Cerris in the pure and mixed samples and main genotypes shared by species of sect. Quercus. Application of different cut-off thresholds revealed that medium-high abundance sequences (>10 or 25) suffice for a net species identification of samples containing one or few individuals. Lower thresholds identify phylogenetic correspondence with all target species in highly mixed samples (analogue to environmental bulk samples) and include rare variants pointing towards reticulation, incomplete lineage sorting, pseudogenic 5S units, and in-situ (natural) contamination. Our pipeline is highly promising for future assessments of intra-specific and inter-population diversity, and of the genetic resources of natural ecosystems, which are fundamental to empower fast and solid biodiversity conservation programs worldwide.

Growing evidence shows that a homozygous 6.7-kb deletion of the novel anti-inflammatory molecule leukocyte immunoglobulin like receptor A3 (LILRA3) is associated with many autoimmune disorders. However, its effects on pathogenesis of inflammatory bowel disease (IBD) have not been clarified yet. LILRA3 is mainly expressed in monocytes, whereas its effects on biological behaviors of monocytes have not been systematically reported. To investigate the association between LILRA3 polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in 378 IBD patients and 509 healthy controls in our study, quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC) were employed to detect the LILRA3 expression in IBD patient blood and intestinal samples. Despite no association of the polymorphism with IBD development was found, LILRA3 expression was markedly increased in IBD patients compared with healthy controls. Human U937 monocyte cell line was employed to establish LILRA3-overexpressing cells and the effects of LILRA3 on the biological behaviors of U937 cells were systematically explored. We found that overexpression of LILRA3 in monocytes led to significant decreases in secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Additionally, LILRA3 abated monocyte migration by reducing the expression of several chemokines and enhanced monocyte phagocytosis by increasing CD36 expression. Furthermore, LILRA3 promoted monocyte proliferation through a combination of Akt and MEK/Erk signaling pathways. We report for the first time that LILRA3 is related to IBD and functions as an anti-inflammatory modulator in U937 cells.