A series of interatomic interactions interpretable as halogen bonds involving I…I, I…O, and I…C(π), as well as the noncovalent interactions I…H and O…O were observed in the crystal structures of 1,2-diiodoolefins dimers according to ab initio calculations and the quantum theory of “atoms in molecules” (QTAIM) method. The interplay between each type of halogen bond and other noncovalent interactions was studied systematically in terms of bond length, electrostatic potential and interaction energy, which are calculated via ab initio methods at the B3LYP-D3/6-311++G(d,p) and B3LYP-D3/def2-TZVP levels of theory. Characteristics and nature of the haologen bonds and other noncovalent interactions, including the topological properties of the electron density, the charge transfer and their strengthening or weakening, were analyzed by means of both QTAIM and “natural bond order” (NBO). These computational methods provide additional insight into observed intermolecular interactions and are utilized to explain the differences seen in the crystal structures.

Spectral analysis and statistical studies were investigated in a semi pilot bubble column using wall pressure sensors in different axial position both in the air–water system and in water–alcohol solutions (ethanol, 2-propanol and 1-butanol). Gas holdup is more important in the zone far enough to the gas distributor. Then volumetric mass transfer coefficient (KLa) was measured for three axial positions. Interesting results show clearly by the average frequency, that regime transition is delayed for the coalescence inhibitor system and more particularly with the increase in the carbon number of the alcohol. Cross correlation and coherence between two pressure sensors signals revealed clearly that the transition of the flow regime starts when the periodicity appears for a certain gas velocity. The results of the gas liquid mass transfer revealed that KLa decreased with addition of alcohol which is explained by Higbie’s theory.

The activity of influenza A at the end of 2019 was higher than previous two years in children younger than 6 years old in Wuhan, China. The 2019-20 seasonal influenza winter outbreak preceded the COVID-19 outbreak, with a higher and earlier peak than that of the 2017-18 and 2018-19 seasons. We speculate this could be due to the earlier CNY holiday season in 2019-20 than in previous two years. We compared these results with those of two previous studies to further discuss the possible interference between influenza and COVID-19 in young children.

Vectors of emerging infectious diseases have expanded their distributional ranges in recent decades due to increased global travel, trade connectivity, and climate change. Transboundary range shifts, arising from the continuous movement of humans and livestock across borders, are of particular disease control concern. Several tick-borne diseases are known to circulate between eastern Uganda and the western counties of Kenya, with one fatal case of Crimean-Congo haemorrhagic fever (CCHF) reported in 2000 in Western Kenya. Recent reports of CCHF in Uganda have highlighted the risk of cross-border disease translocation and the importance of establishing inter-epidemic, early warning systems to detect possible outbreaks. We therefore carried out surveillance of tick-borne zoonotic pathogens at livestock markets and slaughterhouses in three counties of western Kenya that neighbour Uganda. Ticks and other ectoparasites were collected from livestock and identified using morphological keys. The two most frequently sampled tick species were Rhipicephalus decoloratus (35%) and Amblyomma variegatum (30%), and Ctenocephalides felis fleas and Haematopinus suis lice were also present. In total 486 ticks, lice, and fleas were screened for pathogen presence using established molecular workflows incorporating high-resolution melting analysis and identified through PCR-sequencing of PCR products. We detected CCHF virus in Rh. decoloratus and Rhipicephalus sp. cattle ticks and 82 of 96 pools of Am. variegatum were positive for Rickettsia africae. Apicomplexan protozoa and bcteria of veterinary importance, such as Theileria parva, Babesia bigemina, and Anaplasma marginale, were primarily detected in rhipicephaline ticks. Our findings show the presence of several pathogens of public health and veterinary importance in ticks from livestock at livestock markets and slaughterhouses in western Kenya. Confirmation of CCHF virus, a Nairovirus that causes haemorrhagic fever with a high case fatality rate in humans, highlights the risk of under-diagnosed zoonotic diseases and calls for continuous surveillance and the development of preventative measures.

Background and aim of the study: Several studies reported safety and potential benefits of single dose Del Nido cardioplegia (DNC) in selected Adult Cardiac Surgery (ACS) procedures. However, studies are scarce on routine use of DNC in more complex procedures and patients with high risk profile. We sought to compare DNC with cold blood cardioplegia (BC) in all types of ACS including complex procedures. Methods: Data for 305 consecutive unselected patients who underwent ACS procedures (July/2017 to Nov/2019) were included. DNC was routinely used whenever is available (n=231) and if not available, cold BC is used (n=74). All categories of ACS procedures (primary or redo) were included. Repeated measures analysis was performed to compare baseline, peak and trough Troponins levels in both groups. Linear regression analysis was used to identify independent predictors of peak Troponins level. Results: The two groups were comparable in baseline characteristics including euro score (ES II), risk profile and surgical complexity. DNC was associated with lower cardiopulmonary bypass (CPB) and cross clamp times, cardioplegia volume and number of cardioplegia doses (P<.001). Importantly, DNC was associated with lower postoperative Troponin level (P=.001), shorter duration of inotropic support (P=.02) and shorter intensive care unit stay (P=.04). On linear regression analysis, DNC was an independent predictor of lower postoperative peak Troponin (t = -3.5, P<.001). Conclusions: Routine use of DNC in all types of ACS procedures compared to BC was associated with significantly shorter CPB and clamp times, significantly lower post-operative troponin release and shorter duration of inotropic support.

Children with multisystem - Langerhans cell histiocytosis (MS-LCH) that fails to respond to conventional chemotherapy have poor outcomes. Hematopoietic stem cell transplant (HSCT) represents a potential salvage approach. We report a first case of successful haploidentical transplantation in one child with refractory MS-LCH using T cell replete graft and post transplant Cyclophosphamide (PT-CY) from father as a donor. On last follow up he is 21 months post transplant with no signs of disease activity. This case report suggests that T-cell replete haploidentical donor transplantation using PTCY is a feasible and successful curative option for Patients with refractory MS-LCH who have no matched donor.

We have constructed a new bioreactor with reciprocal mixing that is better suited for the cultivation of delicate animal cells. In-silico simulation (computational fluid dynamics) suggested both maximum and average shear stresses in the bioreactor with reciprocal mixing to be remarkably lower than in conventional bioreactor with rotary mixing. Although we could not find any difference in growth speed and cell density between the bioreactors with reciprocal and rotary mixing, we did find cell viability in reciprocal-mixing bioreactor to be retained longer than in rotary-paddle bioreactor. This implied that cell culture in a bioreactor with reciprocal mixing could be prolonged for the production of target proteins. Leakage of lactate dehydrogenase activity into the culture medium was suppressed much more in the reciprocal-mixing bioreactor than in the rotary-paddle one. Production of human tissue plasminogen activator in the former was also observed to be much more than in the latter. Therefore, bioreactor with reciprocal mixing was concluded to be better suited for the cultivation of animal cells and efficient production of proteins, such as antibody drugs and various growth factors.

The regulation of cell density is an important segment in microfluidic cell culture, particularly in the repeated assays. Traditionally, the consistent cell density is difficult to achieve owing to the inaccurate regulation of cell density with manual feedback. A novel microfluidic culture method with automatic feedback is proposed for real-time regulation of cell density in this paper. Here, an integrated microfluidic system combining cell culture, density detection and control of proliferation rate was developed. Interdigital electrode structures (IDES) are sputtered on the microchannel for automatically providing the real-time feedback information of impedance. The most sensitive frequency is studied to improve the detection resolution of the sensing chip. Cells were cultured on the chip surface and the cell density was detected by monitoring the alternation of the impedance. The feedback controller is established by least squares support vector machines (LS-SVM). Then, the cell proliferation rate was automatically controlled using the feedback controller to achieve the desired cell density in the repeated assays. The results show that the standard error of this method is 2.8% indicating that the method can keep consistency of cell density in the repeated assays. This study provides a basis for improving the accuracy and repeatability in the further assays of finding the optimal drug concentration.

The land use changes directly reflected the economic and environmental development status of the region in a certain period, and the indicator can be applied in analyzing the role and economic benefits of various administrative departments. The Yangtze River Economic Belt, China is one of the “three major strategic development regions at the national level” implemented by the nation. The Markov prediction model was introduced to simulate the land use changes in the region and the average accuracy of the simulation was 99.54%. In the simulation the four regional development stages from 1992 to 2018 were identified in the model: primitive development, rapid urban expansion priority, ecological restoration priority and equilibrium on urban expansion and ecological restoration. Various scenarios with different transition probability matrix were characterized on diverse socio-economic conditions. The mean values were introduced in the prediction model. The land use changes in the Yangtze River Economic Belt in 2020-2030 were predicted and the characteristics of the changes in various scenarios were analyzed so as to provide scientific suggestions for decision makers on the sustainable utilization of the land in the densely populated and ecologically sensitive area.

Patients in sub-Saharan Africa generally have poor anticoagulation control. We review the potential reasons for this poor control, as well as the potential solutions. Challenges include the affordability and centralisation of anticoagulation care, problems with access to medicines and INR monitoring, the lack of locally-validated standardized dosing protocols, and low levels of anticoagulation knowledge among health care workers and patients. Increasing numbers of patients will need anticoagulation in the future because of the epidemiological transition in the region. We propose that locally-developed “warfarin care bundles” which address multiple anticoagulation challenges in combination may be the most appropriate solution in this setting currently.

Single cell analysis has numerous potential applications, for instance in the context of myotonic dystrophy type I (DM1). This disease is caused by a CTG expansion in the dystrophia myotonica-protein kinase (DMPK) gene, with CTG expansion length being heterogeneous not only between tissues but also between cells in the same tissue. We studied muscle pathophysiology from five patients with DM1 at single cell level, including RNA foci (i.e., nuclear DMPK-transcribed aggregates that trap proteins) and splicing alterations (caused by trapping of important splicing regulator proteins by the RNA foci). Single cell myoblasts were heterogeneous in RNA foci load, with most showing 0 to 3 foci. The percentage of myoblasts carrying foci differed among patients, ranging from 29 to 99%. We found a significant direct correlation between mean and median number of RNA foci in myoblasts and patients’ endurance capacity (r=-0.975, p=0.005). Although the expression of DMPK and MBNL1 transcripts was variable among the myoblasts, no relationship was found between RNA foci number and their expression in individual cells. CTG size in muscle correlated with patients´ disease onset. In summary, single cell analysis poses some technical challenges but allows an in-depth analysis of heterogeneous molecular alterations in patients with DM1.

The coagulopathy associated with Coronavirus disease 2019 (COVID-19) leads to a thrombotic burden. To date, solely interim thromboprophylaxis guidance have been established, gaps in evidence are remaining, especially for ambulatory COVID-19 patients. We report a case COVID-19 in a patient with Glanzmann thrombasthenia, a rare platelet disorder associated with a high bleeding tendency. Our experience emphasizes the difficulty to manage such a condition, given the balance between thrombotic and bleeding tendencies, and the unavailability of evidence-based guidelines. Moreover, we detail hereinafter how patient’s bleeding disorder made COVID-19 diagnosis very difficult, thus highlighting the limits in actual SARS-CoV-2 molecular assays.

Introduction: Although D-dimer was reported to be elevated in COVID-19 death, few studies about changes in serial D-Dimer Levels with different severity of illness. Early prophylactic anticoagulation contributes to improve patient outcomes in COVID-19, the perception of timing of anticoagulant treatment is mixed. Methods: Retrospective analysis of 38 severity COVID-19 patients, compared changes in serial D-Dimer Levels between low-flow oxygen therapy and higher concentration oxygen therapy. Patients were stratified into two groups distinguished by D-Dimer value in start of anticoagulation treatment, definition D-Dimer=3mg/L of a cut-off value. Compare the improvement within 7 and 14 days, the time to the first appearance of improvement with chest CT and the days of hospital stay between two groups. Results: A total of 38 severe patients who accept anticoagulant therapy were enrolled into the study from consecutive 59 confirmed cases. Regression analysis showed that compared to those D-Dimer≤3mg/L, patients with higher D-Dimer increase the risk (OR=15.697, P＜0.001) to develop to further severe illness. The difference of patient’s improvement within 14 days (P=0.043) was much more significant compared to 7 days (P=0.757) in two groups. The days at the time of CT imaging improvement were 12.1±3.6 days in the D-Dimer≤3, while 16.2±6.4 days in D-Dimer＞3 (p=0.028). The hospital stays in the two groups were 27 (25.5-30.5) days and 28 (27-36.5) days separately (p=0.086). Conclusions: D-dimer is available for the evaluation of illness condition and the timing of anticoagulant therapy in severe COVID-19, and its role should not be ignored and required further study.

The case fatality rate of Covid-19 in pregnancies published so far varies significantly. In our cohort of 515 women we had 3 maternal deaths due to three varying pathologies related to Covid-19. Our first case died due severe ARDS and a superimposed Pneumothorax, our second case the main cause of death was Septic shock and our third case developed Covid-19 encephalitis that resulted in brain death. There is currently only 10 maternal mortality cases described in detail in the literature. All our 3 cases were of South Asian origin, 2 of which had a BMI above 35.

The prenatal diagnosis of fetal anomalies started with the development of X-ray. In 1943, Hartley and Burnet, Radiologists in Manchester (J Obstet Gynaecol Brit Empire,1943;50:1-12), reported a series of 11 cases of “croaniolacunia” or lacunar skull, a condition often associated at births with spina bifida or encephalocele. These cases were all diagnosed in the third trimester of pregnancy and the radiograph features believed to be due to the effect of increased intracranial pressure on the fetal skull of hydrocephaly. Until the end of the 1960s, radiography remained the main technique to diagnose congenital abnormalities. In 1969, Russell (J Obstet Gynaecol Br Commonw,1969;76:345-50), also a consultant radiologist from Manchester, compared the accuracy of antenatal radiology examinations with paediatric reports in the diagnosis of anencephaly and other major neural tube defects, skeletal abnormalities such as achondroplasia and severe exomphalos when associated with rib deformities. Overall, the accuracy of the radiological diagnosis was considered as “strikingly” accurate for neural tube defects with 88 out of 113 cases of anencephaly diagnosed before delivery. Although, the author did not provide the gestational age at diagnosis, the images included in the article indicate that these were obtained in the third trimester. As neonatal care and surgery were in their infancy at the time, the main objective in diagnosing these anomalies was not the fetus but the need to identify antenatally mothers at risk of obstructed labour.Not surprisingly, some of the first publications by the team of Ian Donald in Glasgow were on the antenatal use of ultrasound imaging in the evaluation of the size of the fetal head (Willocks et al., J Obstet Gynaecol Br Commonw,1964;71:11-20). The fetal head was the only structure that could be measured and biparietal diameter the only measurement that could be obtained with the “ultrasound beam” of the first ultrasound machine (Figure). The technique called “cephalometry” was used at the end of the third trimester to assess “growth and maturity” of the fetus and “disproportion” and was found to be more reliable with ultrasound than X-ray. It would be another decade, before ultrasound imaging could reliably identify fetal anomalies such as spina-bifida in the second trimester of pregnancy (Campbell et al., Lancet,1975;1(7920):1336-7). However, the use of ultrasound imaging in the mid-seventies to search for major neural tube defects was always triggered by high levels of maternal serum alpha-fetoprotein. As there were few ultrasound equipment available and few trained operators, this biomarker was to remain for two decades the first line of action in the antenatal screening strategy for spina-bifida. The advent of high-resolution imaging, access low-cost and mobile ultrasound equipment and the training of more specialists and sonographers has moved the antenatal screening and diagnosis of many fetal anomalies to 11-14 weeks of gestation (Ushakov et al., UOG,2019;54:740-5).The systematic review by Drukker et al. (BJOG 2020) brings the focus back to late pregnancy: even in our exciting modern era of early anomaly scanning, a fetal abnormality will still be found in about 1 in 300 women scanned in the third trimester.Word count: 500BJOG since 1902 Perspectives on BJOG-20-0525R1

Algae are promising feedstock of biofuel. The screening of competent species and proper fertilizer supply are of the most important tasks. To accelerate this rather slow and laborious step, we developed an integrated high-throughput digital microfluidic (DMF) system that uses discrete droplet to serve as micro-bioreactor, encapsulating microalgal cells. Based on the fundamental understanding of various droplet hydrodynamics induced by the existence of different sorts of ions and biological species, an incorporation of capacitance-based position estimator, electrode-saving-based compensation and deterministic splitting approach was performed to optimize the DMF bioreactor. Thus, it enables all processes (e.g. nutrient gradient generation, algae culturing and analyzing of growth and lipid accumulation) occurring automatically on-chip especially in a high-fidelity way. The ability of the system to compare different micro algal strains on chip was investigated. Also, the Chlorella sp. were stressed by various conditions and then growth and oil accumulation were analyzed and compared, which demonstrated its potential as a powerful tool to investigate microalgal lipid accumulation at significantly lower laborites and reduced time.

Traditional cell line development is based on random genomic integration of transgenes. Random integration leads to unpredictable expression and results in clonal heterogeneity requiring a tedious screening procedure. Therefore, a new strategy is needed to establish clones that exhibit stable transgene expression. Here, we performed CRISPR/Cas9-mediated site-specific integration (SSI) to incorporate a landing pad (LP; containing mCherry) at a genomic hotspot (Fer1L4) allowing stable and strong expression. Site-specific integration of LP on Fer1L4 was demonstrated by sequencing results representing the swapped sequences in mCherry-expressing cells. We then performed Cre/Lox-based recombinase-mediated cassette exchange (RMCE) to exchange LP with a targeting vector (TV; containing GFP) in clones established by CRISPR/Cas9-mediated SSI. The success of Cre/Lox-based RMCE was evidenced by sequencing results representing the swapped sequences in GFP-expressing cells. Furthermore, the swapped clones expressing GFP was enriched up to 80%, indicating that the efficiency of Cre/Lox-based RMCE would be sufficient to swap pre-existing cassettes with gene-of-interest (GOI). Taken together, our study provides a new platform for Cre/Lox-based RMCE to iteratively establish stable clones from existing ones previously established by SSI at a genomic hotspot.

Cor-triatriatum sinister (CTS) is a rare congenital condition in which the left atrium is divided into two chambers. Patients can present as infants or later in life, which is largely dependent on the size of fenestration between these two chambers. Surgical excision of the membrane is curative. This is traditionally performed through a median sternotomy. Here we report of a case of a 60-year old man who presented to his primary care physician with dyspnea and atrial fibrillation. He was found to have CTS. We performed excision of the left atrial membrane and maze procedure through a left anterolateral mini-thoracotomy with femoral cannulation.

Extracorporeal life support (ECLS) is an expanding technology for patients in cardiogenic shock. Most patients requiring ECLS can be managed with percutaneous veno-arterial (VA) femoral cannulation. Despite sufficient extracorporeal circulatory support, an unclear number of patients develop left ventricular distension which can result in increased wall tension and stress as well as worsening pulmonary edema. Indications to vent the left ventricle can be controversial. When venting is indicated a number of additional procedures may be considered including inotropic support, intra-aortic balloon pump, Impella, balloon atrial septostomy, or placement of a transseptal cannula. We present a unique case of a femoral VA Extracorporeal membrane oxygenation (ECMO) as bridge to transplant (BTT) with left-sided venting using a Bio-medicus NextGen cannula (Medtronic) with a transseptal approach.

Nonspecific Lipid Transfer Proteins (nsLTP2) are small and soluble proteins, which due to their unique features have the ability of binding to lipids and some pharmaceutical compounds, are considered as good options for drug delivery systems. Their stability against proteolysis and thermal denaturation leads to allergenic reactions which limit its clinical usage. The bioinformatics approach was carried out to hydrophobicity and antigenicity analysis of Oryza sativa (Iranian group) nsLTP2. Using Molegro Virtual Docker software, the affinity and binding strength of several fatty acids, steroid-based anti-viral, and anti-tumor drugs with nsLTP2 were identified. Results demonstrated that there is only one transmembrane segment in the nsLTP2 protein sequence which is located in the signal peptide region, also calculating the average antigenicity propensity (AP) of amino acids showed that concurrent mutations of C26N/N53F can reduce the antigenic propensity of these proteins. Furthermore, Abacavir (MolDock Score = -119.348), DHA (MolDock Score = -152.601), and Basedoxifene (MolDock Score = -156.776) could be considered as the best antiviral, phospholipid, and anticancer ligands for it, respectively.

In the present study, the microstructure evolution and material properties variation mechanism of austenitic stainless steel under pre-strain were discussed. A bilinear relationship between material properties and pre-strain was established. Both yield strength and tensile strength of the austenitic stainless increase with the increase of pre-strain, but the increment of yield strength is obviously greater than that of the tensile strength. A critical pre-strain point was put forward. When the pre-strain is lower than critical value, there is only work hardening. And when it is higher than critical value, the material properties are affected by the combined effects of work hardening and martensitic transformation. The effect of critical pre-strain is also found in the study of fatigue limit. The inherent essence of fatigue limit improvement of pre-strained material lies in the comprehensive effect of material phase transformation and plastic deformation strengthening.

Infiltration and soil water content (SWC) are key concerns to agro-hydrological researchers. Understanding of irrigation-induced infiltration and soil water characteristics are fundamental to irrigation management and improving agricultural Water Use Efficiency (WUE) in arid and semi-arid areas. Based on measurements from a test site in Xinjiang, China, numerical simulations have been performed to investigate the infiltration processes under alternating drip irrigation operations. The present study focuses on simulating infiltration physics and analyzing its potential impacting factors, to shed light on the design of irrigation systems that improve WUE. The results show that irrigation schedules, surface sealing, residual water saturation, and soil fractures have significant impacts on SWC patterns for both the irrigation durations and intermittences. Low frequency irrigation with high watering rates should be avoided due to its low irrigation efficiency. Commencing with lower-rate irrigation is probably the best practice for efficient irrigation for shallow-root crops. The soil infiltrability drops exponentially or polynomially with the decrease in permeability of the immediate surface. Introduction of a 5-mm soil surface seal with a permeability of 5 mD leads to about 97.1% reduction in the infiltrability. Residual water saturation Swr or water content has positive correlations with Volumetric soil Water Content (VWC), due to the trapping of the residual water. Enhancement of one-fold magnitude of Swr causes 6.12% and 20.4% higher VWC for the loamy sand, but 7.57% and 5.71% lower VWC for the underlying sandy loam, at the 160 hr and 720 hr respectively. The presence of soil fractures leads to apparent preferential flows in the soil, which cause the wet fronts to penetrate to 115.9% and 53.88% deeper depths at the 160 hr and 720 hr, respectively.

Droplet nuclei are sometimes defined only by size. The Centers for Disease Control and Prevention (CDC) defines that “droplet nuclei are dried residue of less than 5 microns in size” (1) . But it is sometimes explained as: “Small drops of moisture carrying infectious pathogens are called droplet nuclei” (2) . World Health Organization (WHO) defines that “when the droplet particles are >5-10 μm in diameter they are referred to as respiratory droplets, and when then are <5μm in diameter, they are referred to as droplet nuclei” (3) ,not requiring desiccation..The term droplet nuclei needs to be clearly defined in terms of desiccation. For the purposes of this article, droplet nuclei will be discussed using the CDC’s definition of droplet nuclei with a requirement for desiccation. The WHO and CDC’s current position is based on the conventional medical definition that in human exhalation origin, only droplet nuclei can cause airborne transmittion (1) . To date, WHO and CDC suspects but do not officially recognize airborne SARS-CoV-2 transmission (4) . The viruses that the CDC is currently warning about as causing airborne transmission are limited to measles, chickenpox, disseminated shingles, and smallpox(5) . Other viruses are suspected but not confirmed. Suspected case of SARS-CoV transmission via apartment building air (6) , outbreaks of influenza in an airplane delayed on the ground with inoperative ventilation system (7) , and reports of simultaneous COVID-19 outbreaks in large enclosed spaces (8) , suggest that all these enveloped viruses are transmitted by dry droplet nuclei, because it is unlikely that the fine droplets will stay moist for such long distances and time. Wells found that droplets smaller than 100 μm would completely dry out before falling approximately 2 m to the ground(9) .Morawska calculated that “droplets with sizes of the order of 1μ m evaporate within a few milliseconds, even under the conditions of high relative humidity. Droplets of the order of 10 μ m exist for up to a few tens of a second, while very large droplets, 100 μ m in diameter, survive for up to almost a minute” (10) . SARS-CoV-2 and SARS-CoV exhibited similar half-lives in aerosols, with median estimates around 2.7 hours (11) . In this study, all aerosols should have dried out during the course of the process and turned into droplet nuclei. A couple of hours of half-life time should be sufficient for the dry droplet nuclei to be dispersed and become clinically infectious especially in an enclosed environment. The presence of infectious, replicating virions in <1 µm aerosol samples have been shown by showing increases in viral RNA during cell culture of the virus from aerosol samples (12) . As it has been calculated that droplets with sizes of the order of 1μ m evaporate within a few milliseconds(10) , it indicates that SAS-CoV-2 can cause droplet nuclei transmittion. SARS-CoV-2 has been shown not to be inactivated on plastic and stainless steel for a couple of days (11) . Generally, enveloped viruses which has lipid envelope tend to be more persistent at lower relative humidity, while nonenveloped are more stable at higher relative humidities (13).Airborne transmission is meant by most authors to be synonymous with aerosol transmission (14 ). WHO states as follows: “Airborne transmission is defined as the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in air over long distances and time” (7). This statement includes two definitions. First, WHO define that the term “airborne transmission” is limited to transmission by droplet nuclei. Second, WHO define that airborne, droplet nuclei, and aerosol transmission are all synonymous. CDC states that “The definition of an aerosol, as used here, is a suspension of tiny particles or droplets in the air, such as dusts, mists, or fumes.” (15). CDC’s definition requires droplet nuclei to be dry, and airborne transmission is limited to transmission by droplet nuclei.Therefore, aerosol transmission is not synonymous to airborne or droplet nuclei transmission in CDC’s definition. Additionally, in most reports stating SARS-CoV-2 is airborne and/or aerosol-transmitted, the definitions of the terms airborne and aerosol are not clear whether those refer only to dry droplet nuclei or it includes fine, moist droplets floating in the air (14 ).The fact that the definitions of aerosols and droplet nuclei are not uniform worldwide, even between the WHO and CDC, is a huge detrimentIndeed, it is difficult to determine how small and how dry a particle is to be called a droplet or droplet nuclei. If the vagueness of this boundary is a problem, the alternative is to abolish the classification of droplets and droplet nuclei and reclassify them as droplets and aerosols, based solely on how much they are suspended in the air, regardless of how dry they are.Along with the global unification of the definitions of aerosols and droplet nuclei, the above theoretical evidence showing that SARS-CoV-2 are drying-resistant and likely to be airborne transmitted by dry droplet nuclei, should be recognized.

Hyperexcitability-related diseases include epilepsies, pain syndromes, neuromuscular disorders, and cardiac arrhythmias. Sodium channel inhibitors can be used to treat these conditions, however, their applicability is limited by their nonspecific effect on physiological function. They act by channel block (obstructing ion conduction, since the binding site is within the channel pore), and by modulation (delaying recovery from the non-conducting inactivated state). Channel block inhibits healthy and pathological tissue equally, while modulation can preferentially inhibit pathological activity. Therefore, an ideal sodium channel inhibitor drug would act by modulation alone. Unfortunately, thus far no such drug has been known to exist. Here we present evidence that riluzole acts by this “ideal” mechanism, “non-blocking modulation” (NBM). We propose that, being a relatively small molecule, riluzole is able to stay bound to the binding site, but nonetheless stay off the conduction pathway, by residing in one of the “fenestrations” (cavities connecting the central cavity to the membrane phase). Using precisely timed UV pulses to photolabel specific conformations of the channel, we show that association to the local anesthetic binding site requires prior inactivation. We discuss why kinetics of binding is crucial for selective inhibition of pathological activity, and how the NBM mechanism can be recognized using a special voltage- and drug application-protocol. Our results identify riluzole as the prototype of this new class of sodium channel inhibitors. Drugs of this class are expected to selectively prevent hyperexcitability, while having minimal effect on cells firing at a normal rate from a normal resting potential.