Historically in a pandemic the focus has been upon identifying agents that would eliminate the invading species with as little damage as possible to the host. Recently discussion has moved, particularly with COVID-19, from antiviral therapy to delineating the treatment of the host from treatment. With the latter, the approach brings together three concepts; treating the host, the damage response framework and therapeutic repurposing. The integration of these three areas play heavily to the traditional strength of pharmaceuticals in providing a period of stabilization prior to the introduction of subsequent interventions to permit time for the development of novel anti-viral drugs and vaccines . In integrating approaches to repurposing, host treatment and damage response we identified three key properties that a potentially effective repurposed drug must posses by way of a framework. There must be homology with the pathogenesis of the disease, ideally targeted to the conserved pathophysiological outcomes of the vial attack, have a defined locus within the spectrum from prevention to severe disease and finally draw upon the historical dose and safety experience of the repurposed drug. By way of illustration we have mapped therapeutic agents that impact upon the renin angiotensin system using this approach. Collectively this type of analysis reveals the importance of existing data (repurposed information and administrative observational data) and the details of the known pathophysiology of the viral attack are in approaches to treating the host; and with COVID-19 the significance of a pre-existing RAS-mediated inflammatory disposition.

Objective: Patients with coronary artery bypass grafting require special care at home, and not being aware of this care before surgery can cause anxiety. This study aimed to determine the effect of home care training on anxiety and vital signs levels in CABG patients. Methods: This clinical trial study was performed on 80 patients undergoing CABG surgery in Farshchian Hospital in Hamadan, Iran, in January 2020. Samples were selected by convenience sampling and were randomly divided into intervention and control groups. The control group received only routine training, but the intervention group also received two-session training of home care. Data were collected using the Spielberger situational anxiety questionnaire and the vital signs checklist, then analyzed using descriptive and inferential statistics in SPSS software version 16. Results: The results showed that before the intervention, the mean scores of anxiety, heart rate, respiratory rate, temperature, systolic blood pressure, and diastolic blood pressure of the two groups were not significantly different(P>0/05). However, after the intervention, the mean score of anxiety, the heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure of the intervention group was lower than the control group significantly(P<0/05), But the mean temperature of the two groups showed no significant difference(P>0/05). Conclusions: Home care training before surgery reduces anxiety and vital signs, therefore the use of home care training before surgery is recommended in this group of patients.

Anaphylaxis in children is a potential acute life-threatening systemic hypersensitivity reaction. Anaphylaxis fatality rate is estimated to be 0.65% to 2%. Food is the main anaphylaxis trigger in children, notably cow’s milk, peanuts and tree nuts. Mucocutaneous manifestations are observed in more than 90% of cases, but it is not essential for diagnosis. Deaths are rather secondary to the laryngeal edema, observed in 40-50% of cases. Personal history of asthma, allergy to particular foods such as peanuts and tree nuts, and adolescence are known risk factors for anaphylaxis and more severe reactions. Epinephrine (adrenaline) is the medication of choice for the first-aid treatment of anaphylaxis. However, adrenaline auto-injectors (AAIs) are commercially available in only 32% of world countries. There are still considerable unmet needs in the field of anaphylaxis in children. Therefore, the Montpellier WHO Collaborating Centre aims to start the global actions plan applied to anaphylaxis.

Mapping of non pulmonary vein triggers for the initiation of atrial fibrillation can be complex and time consuming. We describe a technique where templates are created by pacing from different locations with the right and left atria during sinus rhythm whilst positioning a high definition (HD) Grid catheter along the posterior wall of the left atrium and recording the activation sequence. Following this AF is initiated using decremental atrial pacing and the administration of intravenous isoprenaline and the activation across the HD Grid is compared with the templates. In our case series this appears to easily locate the focus source for the initiation of AF.

There is currently no correlation between substrate mapping during atrial fibrillation and sinus rhythm. We sought to determine the correlation between the mean voltage recorded during atrial fibrillation and sinus rhythm at different times up to a total duration of 30 seconds. We found that the most accurate correlation between the mean voltage occurred over a period of 10 seconds recording. Although in average the mean voltage during atrial fibrillation is lower than during sinus rhythm this represents the most accurate comparison between voltage mapping during atrial fibrillation and sinus rhythm.

Abstract Introduction: Therapies for substrate-related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. Methods: A nanocellulose-carbon nanotube conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. Results: The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The DC conductivity under aqueous conduction was 4.3·10-1 S/cm. In 4 canine hearts, when compared to the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation similar to baseline in all 4 hearts. Gross specimen examination demonstrated retention of the hydrogel within the tissue. Conclusions: This proof-of-concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long-term retention and biocompatibility of the hydrogel through in vivo experimentation.

Introduction Anatomical studies demonstrate significant variation in cavotricuspid isthmus (CTI) architecture. We hypothesised that ablation index (AI) may further our understanding of energy delivery across the CTI. Methods 38 patients underwent CTI ablation at two Cardiothoracic hospitals. Operators delivered 682 lesions in total with a target AI of 600Wgs. Ablation parameters were recorded every 10-20ms. Post hoc, Visitags were trisected according to CTI position: inferior vena cava (IVC), middle (Mid), or ventricular (V) lesions. Results There were no complications. 97.4% of patients (n=37) remained in sinus rhythm at 6.6±3.3 months’ follow-up. For the whole CTI, peak AI correlated with mean impedance drop (ID) (R2=0.89, p<0.0001). However, analysis by anatomical site demonstrated a non-linear relationship Mid CTI (R2=0.15, p=0.21). Accordingly, whilst mean AI was highest Mid CTI (IVC: 473.1±122.1 Wgs, Mid: 539.6±103.5 Wgs, V: 486.2±111.8 Wgs, ANOVA p<0.0001), mean ID was lower (IVC: 10.7±7.5Ω, Mid: 9.0±6.5Ω, V: 10.9±7.3Ω, p=0.011), and rate of ID was slower (IVC: 0.37±0.05 Ω/s, Mid: 0.18±0.08 Ω/s, V: 0.29±0.06 Ω/s, p<0.0001). Mean contact force was similar at all sites, however temporal fluctuations in contact force (IVC: 19.3±12.0mg/s, Mid: 188.8±92.1mg/s, V: 102.8±32.3mg/s, p<0.0001) and catheter angle (IVC: 0.42°/s, Mid: 3.4°/s, V: 0.28°/s, p<0.0001) were greatest Mid CTI. Use of a long sheath attenuated these fluctuations and improved ablation efficacy. Conclusions Ablation characteristics vary across the CTI. At the Mid CTI, operators should appreciate that higher AI values do not necessarily deliver more effective ablation; this may be explained by localised fluctuations in catheter angle and contact force.

Premature ventricular contractions (PVCs) originating from anterior interventricular septum is frequent and can be cured by radiofrequency catheter ablation (RFCA). Left ventricular diverticulum (LVD) often correlates with ventricular tachyarrhythmias and produces a higher risk of sudden cardiac death. Here, we report the case of a 29-year-old woman with a rare combination of PVCs originating from anterior interventricular septum and LVD who successfully received RFCA.

Objective: To determine the contribution that pre-labor cesarean (cesarean performed without attempting vaginal birth) makes to all cesarean births, and to cesarean births within subgroups of the pregnant population. Design: Retrospective cohort study. Setting: 15 hospitals in the Pacific Northwest of the United States. Population: Births at 23+0-42+6 weeks’ gestation between January 1, 2017 and March 31, 2018. Methods: Review of clinical data abstracted from medical records. Main Outcome Measures: The contribution of pre-labor cesarean to all cesareans and to primary cesareans. The indications for pre-labor primary cesarean in singleton term cephalic pregnancies. Results: Of 32756 births in the study population, 10290 (31.4%) were cesarean births. Pre-labor cesareans represented: 63.7% of all cesareans; 32.4% of cesareans in nulliparas; 58.7% of cesareans in multiparas with no history of cesarean; and 20.0% of all births. Pre-labor cesareans constituted 68.3% (2418/3542) of cesareans in singleton term cephalic multiparas with one previous cesarean, 89.4% (356/398) of cesareans in multiple pregnancies, and 53.2% (216/406) of cesareans in twin pregnancies where Baby A was cephalic. In singleton term cephalic pregnancies with no previous cesarean 18.3% (674/3682) of cesareans were pre-labor and suspected macrosomia (28.9%) and maternal request (18.1%), jointly accounted for 47.0% of indications for these surgeries. Conclusions: Cesarean without attempting vaginal birth is a major contributor to both primary and repeat cesarean birth rates. Greater tracking of the rate and indications for these cesarean births may be important in the effort to understand and potentially reduce the primary cesarean birth rate.

Multiple impeller reactors are widely used due to their advanced gas utilization and an increased volumetric mass transfer coefficient. However, with the application of Rushton impellers, gas dispersion efficiency varies between the bottom and the upper impeller levels. The present study analyzes the individual flow regime, power input and gas hold-up in each compartment of a reactor equipped with four Rushton impellers. The results indicate that the pre-dispersion of the air introduced by the bottom impeller plays a key role in a better gas retention efficiency of the upper impellers. In contrast, a flooded bottom impeller adversely affects the gas dispersion of all impellers. A novel analysis of the bubble flow in the dispersed state via a two-phase CFD model reveals that a more homogenous distribution of air bubbles in the upper compartments leads to high compartment gas hold-up values, but fewer bubbles in the vicinity of the impellers. The measured and simulated data of this study indicate that the upper impellers' efficiency mostly depends on the flow regime of and the pre-dispersion by the bottom impeller rather than on the upper impellers' flow regimes. These results contribute to the understanding of essential mixing processes and scaling of aerated bioreactors.

Background and Aims- A fracture and retention of guidewire after cardiac resynchronization therapy device implant has not been reported so far, although it is an uncommon but known complication during cardiac interventions like percutaneous coronary interventions and other cardiac catheterization procedures. Methods- A 53 years old female patient presented to us, who had been diagnosed as a case of dilated cardiomyopathy with severe left ventricular dysfunction and underwent cardiac resynchronization therapy (CRT-D) device implant three years back and subsequently underwent lead replacement 6 months back due to lead dysfunction, with severe pain over the left arm and shoulder for last 1-2 days. On evaluation, it was found that she had a coronary guidewire which might have fractured and retained inadvertently in previous surgical procedure and has caused her symptoms that might have been aggravated by the movements of her arm. Emergency surgical exploration was done and the guidewire which was impacted in deltoid muscle was removed. Results, and Conclusion- We are reporting the case due to a very unlikely and unusual delayed presentation of retained intervention guide-wire post cardiac resynchronization therapy, retrieved from left deltoid muscle.

Percutaneous coronary interventions (PCI) have an established position in the management of patients presenting with acute coronary syndromes and stable coronary artery disease with low complications rates. We present the case of a 67-year-old male referred for urgent coronary catheterization intervention with anterior wall ST-elevation myocardial infarction diagnosis. After stent implantation, the wires were removed however a part of the wire was entrapped in the coronary artery. The metallic coil covering the core of the angioplasty wire was left in proximal part of LAD and protruded into the aortic root. Patient was referred for emergency surgical procedure that was performed through median sternotomy in cardiopulmonary bypass (CPB) and moderate hypothermia. After transverse aortotomy, the foreign body of 7 cm in length was found irremovable, it was transected and left in the proximal portion of the left main coronary artery (LM). The decision to perform revascularization of LAD, CX and RCA was undertaken. The estimated graft blood flow measurements were satisfactory with the values of 7 mL/min in LIMA-to-LAD graft, 39 mL/min in SVBG-to-CX and 43 mL/min in SVBG-to-RCA, respectively. The patient’s postoperative course was uneventful. Cardiac surgery is a reasonable method of treatment in patients with coronary artery disease and PCI complicated with entrapment of broken guidewire protruding in aortic root.

Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. However, the landscape of IDH mutations in pan-cancer has not been fully characterized. Tissue or blood samples were subjected to next-generation sequencing (NGS) for detection the IDH mutation. A total of 28.868 patients from more than 20 solid tumor species were analyzed. 374 cases (1.30%) with IDH mutations were identified. Among all the IDH mutations cases, 80 (21.4%) were biliary tract cancer, 80 (21.4%) were lung cancer, 57 (15.2%) were liver cancer and 42 (11.2%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 0.81% cases and 0.47% cases, respectively. TP53, PBRM1 and BAP1 were the most significantly mutated genes in biliary tract cancer which were different from others cancer. Moreover TMB were significantly higher in lung cancer, colorectal cancer and gastric cancer than biliary tract cancer (p= 0.0164, p <0.0001, p= 0.0067, respectively) and biliary tract cancer patients with IDH mutation had lower TMB compared with wild-type IDH. Somatic IDH mutation was found in multiple solid tumors and IDH would be a driver gene in biliary tract cancer.

Objective To perform a cost utility analysis of prophylactic antibiotics compared with a placebo in preventing maternal infection after operative vaginal birth. Design Economic analysis based on the findings of the ANODE trial, a multi-centre randomised placebo‐controlled trial. Setting Twenty-seven hospital obstetric units across the UK. Population or Sample Women who underwent operative vaginal delivery after at least 36 weeks of gestation. Methods A cost utility analysis from the perspective of the National Health Service was performed. To inform the decision analysis, a decision tree was constructed to calculate an incremental cost effectiveness ratio (ICER). Two one-way sensitivity analyses were conducted. Main Outcome Measures Difference in quality of life and cost between patients given the antibiotics and the placebo. Quality of life scores were reported EQ-5D-5L measurements from the ANODE trial. Results The ANODE trial reported a statistically significant reduction in infection rates with the co-amoxiclav intervention, this was found to yield an improvement of 0.017 QALYs over the placebo1. The cost to the NHS of the intervention was also lower at £120 over 6 weeks compared to the placebo’s £194. This gives an ICER of -£4403.14/QALY. Sensitivity analysis confirmed that the intervention was dominant. Conclusions A prophylactic dose of co-amoxiclav following operative vaginal delivery is a cost-effective intervention, offering improved QoL whilst also reducing overall costs over a 6-week time period. Tweetable abstract Prophylactic antibiotics are a cost-effective way to reduce maternal infection after operative vaginal delivery.

Objective: To determine the association between HDP and cardiovascular mortality. Design: Cohort study Setting: Population based using the Dutch National Birth Hospital Registry linked with the National Death Registry. Population: All women who gave birth between 1995 – 2015 Methods: Cox-regression models with hazard ratios (HR) and survival curves were executed. Main outcome and measures: The cardiovascular mortality risk after HDP was analyzed. Cardiovascular mortality-risk was analyzed in women with a history of HDP in one or more pregnancies compared to women without a history of HDP. In a subgroup of this cohort the effect of HDP on cardiovascular mortality was analyzed using only the nulliparous pregnancy of women. Results: Women were followed for a mean time of 10.4 years. Of 1,625,246 parous women 21.9% had a history of HDP. Gestational hypertension (18.1%) was associated with an aHR of 2.13 (95% CI: 1.91 – 2.38) for CVM. Preeclampsia (3.8%) was associated with an aHR of 3.35 (95 %CI: 2.80 – 4.00) for CVM. Cardiovascular mortality risk was highest in women with a history of HDP combined with a preterm birth (<37 weeks) and a growth restricted child (

Introduction The coronavirus disease 2019 (COVID-19) pandemic has placed personal protective equipment (PPE) for healthcare workers (HCW) in the spotlight. HCW’s face has been reported to be the body part most commonly contaminated by body fluids. The aim of this narrative review to examine the current evidence on face shield as a PPE for droplet or aerosol prevention. Methods A literature search was conducted on the PubMed, MedLine, and Embase databases, with the keywords “face shield”, “visor”, and “droplet precaution”. Bibliographic search was also undertaken. Results Respiratory droplet is particle with diameter greater than 5µm, while aerosol are ≤5µm according to the World Health Organisation. However, infection is not neatly separated into the dichotomy of droplet versus airborne transmission route. Modelling and simulation have shown the importance of the conjunctival mucosa as a route of transmission of disease in blood splashes, droplets and aerosols containing virus. The limited reports from SARS, COVID-19 and influenza season supports its use. However, HCW do not routinely use face shield if they consider the procedures to be unlikely to be associated with potential contamination. They also erroneously believe that prescription glasses is adequate protection. The issues associated with eye shield use, may be less of a problem with face shield. Conclusion Transmission of viruses is multimodal, and the conjunctival mucosa presents a real risk for viral transmission. Eye and face protection is important to prevent transmission of COVID-19.

Objective : To evaluate short and long term results of stapes surgery in patients with Osteogenesis imperfecta (OI). Design: Retrospective case series. Setting: Tertiary referral center Patients: 18 primary stapes surgeries were performed in 11 hearing-impaired OI patients with evidence of stapes fixation. Intervention: Mainly CO2 laser stapedotomy with Teflon piston prosthesis. Main Outcome Measures: Pre-operative and post-operative audiograms at one month and at least one year Results: The main operative findings were stapes fixation, thickened footplate and fragile or fractured stapes crura. No revision surgery was necessary. Hearing improvement was achieved in 94% of the cases. We obtained an air-bone gap closure to within 10 dB in 46% of the cases and to within 15dB in 92% of the cases at one year follow up. The mean hearing gain in air conduction (at 0.5, 1, 2 and 4 kHz) was 18.4 dB at one month and 22.4 dB at one year. Conclusion: Stapes surgery in OI gives good results with few complication in our series. A hearing gain is often obtained in spite of the sensorineural hearing loss caused by the natural progression of the disease

Key Points 1. Women in different periods of physiological cycles, the levels of sex hormones in their body will change significantly, which had correlated to SSNHL. 2. There were significant differences in the average hearing threshold of subjects in different periods, and the average hearing threshold in follicular periodwas significantly lower than that in menstrual period , luteal period and menopause 3. There was a correlation between the subjects at different periods and the severity of SSNHL and the SSNHL severity was the slightest in the follicular period according to the mean rank value. 4. The analysis of SSNHL typing of subjects at different periods were variously . 5. The results of this study can explain the effect of sex hormone on SSNHL to a certain extent, and we will further explore the relationship between sex hormone levels and SSNHL, in order to provide more support for the diagnosis and treatment of SSNHL.

The novel coronavirus SARS-CoV-2 was declared a pandemic on March 11, 2020. It utilizes angiotensin-converting enzyme 2 (ACE2) receptor in renin-angiotensin system (RAS) for viral entry. ACE2 is identified in female and male reproductive systems and reports of multi-organ involvement has led to uncertainty regarding its effects on reproductive systems and fertility. We review existing literature regarding function of ACE2 and RAS in reproductive systems to postulate the implications SARS-CoV-2 may have on fertility and assisted reproductive technology (ART) outcomes. ART guidelines from different fertility societies are provided for management of ART patients and for ART laboratory regulations.

Background Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) were the most usual types of allergic conjunctivitis. House dust mites were the most common sensitization agents for SAC and PAC. This study aimed to explore SAC and PAC risk factors in children. Methods We recruited 176 children suffering from SAC or PAC and 131 control subjects in southwest China. A questionnaire , several eye exams and  the skin prick test (SPT) were performed.The scores of the symptoms/signs were recorded. Results The percentage of children that had ever been breastfed in the case group was lower than in the control group (P<0.05). The rate of parental allergy history in the case group was higher than for the control group (P<0.01). Compared with the control group, the case group was more likely to have other systemic allergic diseases (P<0.01).The incidence rate  of adenoidal hypertrophy (ATH)  in case group was higher than control group (P<0.05). The ocular symptoms and signs scores had significant correlation to the course (P<0.05), but  no correlation to the SPT results (P>0.05). Conclusion Allergic conjunctivitis may coexist with a variety of allergic diseases, and SAC and PAC may be a risk factor for ATH. Breastfeeding should be recommended, as it may be an alleviating factor for allergic diseases, especially for children of parents with a history of allergic diseases. The disease severity is closely related to its course. Therefore, to avoid difficulty in treatment caused by the aggravation of symptoms and signs, timely antiallergic treatment was recommended.

To greatly expand the druggable genome, fast and accurate predictions of cryptic sites for small molecules binding in target proteins are in high demand. In this study, we have developed a fast and simple conformational sampling scheme guided by normal modes solved from the coarse-grained elastic models followed by atomistic backbone refinement and sidechain repacking. Despite the observations of complex and diverse conformational changes associated with ligand binding, we found that simply sampling along each of the lowest 30 modes is near optimal for adequately restructuring cryptic sites so they can be detected by existing pocket finding programs like fpocket and concavity. We further trained machine-learning protocols to optimize the combination of the sampling-enhanced pocket scores with other dynamic and conservation scores, which only slightly improved the performance. As assessed based on a training set of 84 known cryptic sites and a test set of 14 proteins, our method achieved high accuracy of prediction (with area under the receiver operating characteristic curve > 0.8) comparable to the CryptoSite server. Compared with CryptoSite and other methods based on extensive molecular dynamics simulation, our method is much faster (1-2 hours for an average-size protein) and simpler (using only pocket scores), so it is suitable for high-throughput processing of large datasets of protein structures at the genome scale.

Yeast has been engineered for cost-effective organic acid production through metabolic engineering and synthetic biology techniques. However, cell growth assays in these processes were performed in bulk at the population level, thus obscuring the dynamics of rare single cells exhibiting beneficial traits. Here, we introduce the use of monodisperse picolitre droplets as bioreactors to cultivate yeast at the single-cell level. We investigated the effect of acid stress on growth and the effect of potassium ions on propionic acid tolerance for single yeast cells of different species, genotypes and phenotypes. The results showed that the average growth of single yeast cells in microdroplets was identical to those of yeast populations grown in bulk, and microdroplet compartments do not significantly affect cell viability. This approach offers the prospect of detecting cell-to-cell variations in growth and physiology and is expected to be applied for the engineering of yeast to produce value-added bioproducts.

Mitral ring dehiscence is a rare clinical condition and may result in the recurrence of severe mitral regurgitation(MR). Echocardiography has a critical role in the diagnosis. In this case, a patient with prosthetic mitral ring dehiscence was evaluated with transesophageal echocardiography and demonstrative images have been obtained. Interestingly, two different MR jets, first one from the perimitral ring and the second one from the basal portion of the posterior mitral leaflet(PML) were present. Most likely, suturing of the mitral ring to the basal portion of the PML, which is an unexpected condition, caused to MR after the ring dehiscence

Introduction: Dental caries is an infectious disease with predominantly of cariogenic bacteria such as Streptococcus mutans (S. mutans). Xylitol is considered as one of the effective agents that can limit this dental infection. In this randomized, placebo-controlled trial, we aimed to evaluate the potential reflection of short-term xylitol consumption on pro-inflammatory cytokines (TNF-, IL-6 and IL-8) and S. mutans counts by ELISA and qPCR (Quantitative real-time PCR), respectively. Methods: In this study, 154 participants were assigned to two groups, control and xylitol. Dental examination, saliva and swab samples were done at baseline and at 3-week for clinical and microbiological assessment. Results: In xylitol group at the end of 3-week, gingival and plaque index scores were significantly decreased with respect to baseline values (p<0.001 and p<0.05, respectively). The salivary concentration of TNF-, IL-6 and IL-8 were statistically declined at 3-week, more so than those at baseline in xylitol group (p<0.001). S. mutans expression was reduced about 5-fold at 3-week use of xylitol and it was a statistically significant difference compared to baseline (p<0.001). Conclusion: Intriguingly, even short-term consumption of xylitol might play a favorable role in maintaining the oral health status, possibly as a result of decreasing the release of pro-inflammatory cytokines and the counts of S. mutans. Nonetheless, this investigation warrants further endorsement.