Objective: To explore a new method of differential diagnosis of fetal double aortic aorta (DAA) and right aortic arch with mirror-image branches (RAA-MB). Methods: Clinical data and prenatal echocardiographic features of the DAA (n = 22) and RAA-MB (n = 65) confirmed by postnatal or autopsy findings were analyzed retrospectively. The angles between the two aortic arches in the DAA group and between the right aortic arch and the mirror branch were measured. The differences between both groups and differential diagnosis value of the angles were compared and analyzed based on the ROC curve. Results: Left-sided DAA’s proportion (100%) was higher in the double aortic arch group (32.3%) than in the RAA-MB group, (P ＜ 0.05). The proportion of conotruncal anomalies is higher in the RAA-MB group (64.6%) than in the DAA group (18.2%) (P ＜ 0.05). There was a significant difference in the angles between both groups (DAA: 50.3° ± 8.3° vs RAA-MB: 82.9° ± 13.8°) (P < 0.01). When the cut-off value was 62.8°, the sensitivity and specificity of differential diagnosis were 95.5% and 96.9%, respectively. Conclusions: Distinguishing the angle measurement between DAA and RAA-MB is helpful in prenatal prognosis. We recommend a cutoff value of 62.8°.

Background: The lower respiratory tract infections remained the deadliest communicable disease worldwide. The relationship between cardiovascular diseases and viral infections is well known, namely myocarditis. AH1N1 influenza pandemic showed an association with developing acute cardiovascular disease, including ischemic events. Besides, the new pandemic of SARS-CoV2 became a new challenge for cardiovascular health. In early reports showed cardiac damage in patients infected with SARS-CoV2. This study aimed to describe the clinical characteristics with an emphasis on cardiovascular compromises of COVID-19 patients. Moreover, to compare with outbreaks of influenza AH1N1 to identify prognostic factors of severity. Methods: A cross-sectional study, 72 subjects with a confirmed diagnosis of COVID-19 was included, Subjects were evaluated in two groups; those hospitalized and those who required Intensive Care Unite (ICU). The data from different AH1N1 outbreaks were obtained from Velazquez et al. Results: Thirty-four subjects were admitted to ICU. Subjects at ICU, have greater levels of high sensible troponin, D dimer, creatinine, and leukocytes, than hospitalized subjects. The lymphocytes count where diminished in 85.29% of ICU subjects. SARS-CoV2 disease patients were more than one-decade older than patients in the influenza outbreaks. In SARS-CoV2 subjects the overweight and obesity proportion is half than in the influenza outbreaks; there is a big proportion, more than 6 times, of diabetes mellitus in SARS-CoV2 subjects. Conclusions: Viral respiratory infection disease as SARS-CoV2 is a significant risk factor for acute ischemic, functional, and structural cardiovascular complications.

An outbreak of COVID-19 has spread worldwide, and it is urgent to evaluate risk factors associated with severe cases. We aimed to identify risk factors for severe patients with COVID-19. A total of 52 patients with COVID-19 admitted to Henan Provincial People’s Hospital were enrolled in this study, and patients’ information was extracted from electronic medical records. The severity of symptoms of COVID-19 was divided into “mild” and “severe.” Univariate analysis was used to select potential risk factors. A risk model was constructed using multivariable logistic regression analysis. Advanced age (OR = 1.098, 95% CI = 1.020-1.183) and number of comorbidities (OR = 6.067, 95% CI = 1.078-34.143) were significant risk factors for severe patients with COVID-19. The comorbidities included hypertension, diabetes, cardiovascular disease, respiratory disease, and past surgical history. A risk score was developed based on this model, and the developed risk prediction model had good discriminative power and was well-calibrated. This study indicates that advanced age and comorbidities are risk factors for severe patients with COVID-19. More attention should be paid to high-risk patients during hospitalization.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2), the causative agent of the ongoing pandemic of COVID-19 has already marched across 210 countries globally. This novel coronavirus is highly infectious and left us with no available cure and only with containment option. To understand the molecular epidemiology and vaccine design, genetic sequences from different regions are published and analyzed. Here, the first published whole genome sequence of Bangladesh was compared with Asian countries as well as representative strains from across the globe. Phylogenetic analysis of the first Bangladeshi genome, that was published on May 12, 2020 revealed at least 9 Single nucleotide polymorphisms from the Wuhan, China strains and 2 of these mutations are novel compared to the strains analyzed. Among the novel mutations nucleotide 1163 mutation is very novel when compared with all the genomes deposited at Global Initiative on Sharing Avian Influenza Data (GISAID). However, the other mutation at nucleotide 17019, mutation NSP13 E261D is occurred second time after a strain from Austrian patient showed the similar mutation. Structure and screening results of both novel mutation were discussed in detail. Further analysis of these identified novel mutations will boost the understanding of the behavior of SARS-CoV-2 in this region and vaccination and drug development programs would be beneficial.

Targeted therapies are increasingly used in the management of pediatric low grade glioma. How-ever for patients who show resistance to these treatments, limited options are available. We pre-sent the case of a patient with BRAFV600 mutated low grade glioma who showed progression on a combination of trametinib and dabrafenib. Discontinuation of treatment was associated with a life-threatening deterioration and reintroduction of targeted therapy had no effect. The patient eventually showed a dramatic response to TPCV (thiguanine, procarbazine, CCNU and vincris-tine) , which suggests a role of chemotherapy in these situations.

Bioprocess optimization for cell-based therapies is a resource heavy activity. To reduce the associated cost and time, it is advantageous to carry out process development in small volume systems, with the caveat that such systems be predictive for process scaleup. The transport of oxygen from the gas phase into the culture medium, characterized using the volumetric mass transfer coefficient, kLa, has been identified as a critical parameter for predictive process scaleup. In both large- and small-scale bioreactors, kLa is controlled via mixing, with the method employed dependent upon the size of the reactor. However, existing microplate bioreactor platforms, beneficial for their low working volumes and throughput and automation capabilities, struggle to achieve desired kLa for mammalian cell cultures. Here, we describe the development and testing of a 96-well microplate with integrated Redbud Posts to provide mixing and thus enhanced kLa. Mixing characteristics were investigated, with actuating Redbud Posts shown (visually) to increase convective transport while producing enhanced kLa, providing means to mimic macroscale mammalian cell growth conditions at the microscale. Improved cell growth rates with mixing was demonstrated for two cell types, indicating the potential for this technology to play a valuable role in early stage bioprocess development and optimization.

Background: Bird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. Objective: The aim of this study was to clarify the utility of serum IgG (sIgG) and serum IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research. Method: We performed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients. Results: The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by ROC analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85-91% and 73-80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48-61% and 73-80%, respectively. Conclusion: The measurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.

Brain activation after nasal histamine provocation in house dust mite allergic rhinitis patientsCallebaut I1, Steelant B1, Backaert W1, Peeters R2-3, Sunaert S2-3, Van Oudenhove L4-5*, Hellings PW1*1Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium2Department of Imaging & Pathology, KU Leuven, Leuven, Belgium3Department of Radiology, University Hospitals Leuven, Leuven, Belgium4Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism, and Ageing (CHROMETA), University of Leuven, Belgium5Cognitive and Affective Neuroscience Laboratory (CANlab), Center for Cognitive Neuroscience, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA*Joined senior authorshipTo the editor . The nasal mucosa is armed with a complex nervous system of sensory, sympathetic and parasympathetic nerves, allowing swift defensive responses to physical and chemical stimuli. In allergic rhinitis (AR) patients, nasal allergen deposition leads to mast cell activation with release of allergic mediators such as histamine. Apart from its direct effects on the surrounding tissue, histamine also activates sensory nerve endings giving rise to symptoms like sneezing, rhinorrhoea, and/or congestion(1). Activated nasal sensory nerves transmit action potentials to their cell bodies in the trigeminal ganglion and further to the midbrain where secondary synapses lead to the generation of central reflex signals. Despite activation of neural pathways in AR(2), it is not known which particular regions in the brain are activated by different nasal stimuli. Clinical studies using Positron Emission Tomography scans indicate that there is no isolated itch center in the brain but that different cortical centers are involved in the processing of itch(3, 4). Activation of the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and the inferior paretial lobe partly explains the connection between itching and the related reflex of scratching(4). Using functional magnetic resonance imaging (fMRI), the activation of the superior temporal gyrus, insula and nucleus caudate following painful intranasal trigeminal stimulation has been shown(5). When asthmatic patients are challenged with metacholine or allergens, activity in ACC and insula was associated with markers of bronchial inflammation and obstruction(6).To fill the abovementioned knowledge gap, a prospective, single-blind, cross-over study was designed to investigate brain responses to nasal histamine provocation in healthy volunteers and AR patients.Eight house dust mite (HDM) AR patients and 7 non-allergic healthy controls (HC) were recruited at the outpatient clinic for Otorhinolaryngology of University Hospitals Leuven. HDM allergy was confirmed by a skin prick test. Relevant nasal anatomic abnormalities or rhinosinusitis were ruled out by nasal endoscopy. Non-allergic HC showed a negative skin prick test for all the tested allergens, showed no nasal symptoms and had normal nasal endoscopy. Patients of <18 and >50 years of age, having used nasal or oral steroid treatment <6weeks prior to the study or nasal or oral antihistamine treatment <4weeks prior to the study were excluded, as well as those with past or ongoing immunotherapy for HDM, asthma, smoking and clinical signs of rhinosinusitis or anatomic nasal deformities. Informed consent was signed by all participants. The study was approved by the local medical ethics committee of the University Hospitals Leuven (B322201215751).All HC and AR patients underwent a nasal provocation by means of a canulla placed under the nose with either nebulized sham solution (saline) or with histamine for 5 minutes while in supine position in the MR scanner on 2 separate days with a minimum of 1 week in between, and in a single-blinded and random order. An aerosol of 10 ml histamine HCl (16 mg/ml) or 10 ml saline was delivered via the canulla by means of air (8 bar) after 10 minutes of baseline scanning in a pharmacological (ph)MRI design. This concentration of histamine was chosen as optimal dose after a pilot study in 3 HCs, 1 birch and grass pollen AR patient and 1 HDM AR patient where the dose of histamine resulted in a reduction of 20% in the Peak Nasal Inspiratory Flow (PNIF). Moreover, patients did not had the urge to sneeze at this concentration, as was the case for the dose of 32 mg/ml.PNIF values were used for measuring nasal flow at baseline and after the nasal provocation at the end of the phMRI scan, as recommended(7). The best value out of three consecutive measurements with a variability of <10% was recorded. Changes in PNIF from baseline to post-provocation were compared between conditons (histamine & saline) as well as between groups (patients & controls) using marginal linear mixed models.phMRI data were preprocessed and analyzed as described previously(8, 9). The effect of interest for the present study was the group (patient versus controls)-by-substance (histamine versus saline)-by-time interaction effect, comparing the time-course of the brain response to histamine vs saline provocation between AR patients and controls. A whole-brain voxel-wise FWE-corrected threshold of p<0.05 was used combined with an extent threshold of k=10 voxels (corresponding to pFWE<0.001 at cluster level).In total, 8 HDM AR patients (5 females and 3 males) and 7 HC (5 females and 2 males) were recruited with a mean age of 22.5 ± 0.72 and 23.8 ± 1.11 years respectively. One female HDM AR and two female HC were excluded due to excessive head movement during MR scanning.After nasal provocation with saline, no significant decrease in PNIF was found compared to baseline in both groups (AR: 135 ± 61.82 l/min vs 137.5 ± 44.88 l/min, p=0.74; HC: 120 ± 36.74 vs 129 ± 31.30, p=0.46). Nasal provocation with histamine induced a significant decrease in PNIF in both HDM AR patients (158.8 ± 71.55 l/min vs 112.5 ± 83.67, p=0.0053) as well as in the HC (134.2 ± 27.64 l/min vs 85.83 ± 40.55, p=0.002).The analysis on PNIF values showed a significant condition-by-time (pre- to post-provocation) interaction effect (F(1,11)=28.8, p=0.0002), driven by a significant decrease in PNIF after histamine (-47.30±8.87, pHolm=0.0004), but not after saline (-5.81±5.96, pHolm=0.35) in the entire sample. No significant group-by-condition-by-time interaction effect was found (F(1,11)=0.09, p=0.78) indicating that the decrease from baseline after histamine compared to saline did not differ between patients and controls, with a significant decrease from baseline after histamine but not saline in both groups (p=0.002 and p=0.015, respectively).Brain regions showing a differential response to histamine versus saline in AR patients versus HCs included bilateral mid-/posterior insula, right anterior insula, bilateral postcentral/superior temporal gyrus/rolandic operculum (including secondary somatosensory cortex), bilateral putamen, left cerebellum (crus 1 & 2), right mid-occipital gyrus, bilateral medial orbital gyrus/gyrus rectus, and right middle/superior frontal gyrus (ventrolateral prefrontal cortex) (Table 1,Figure 1). Most of these differential responses were due to a stronger activation in controls vs AR patients, except for the right anterior insula, right middle occipital gyrus, right middle/superior frontal gyrus, and left cerebellum, where a stronger activation was observed in AR patients.

Leishenshan Hospital was an urgently built filed hospital in Wuhan only for treating coronavirus disease 2019 (COVID-19) patients. From the 8th of February it received the first cohort of patients until the closure day, 15th of April, it totally accepted 2011 COVID-19 patients including 20.9% severe and 79.1% non-severe cases with a case fatality rate (CFR) 2.2% (95%CI 1.6-3.0%). Totally 1917 (95.3%, 95%CI 94.3-96.2) patients were cured with a recovery rate of 86.2% in severe group and 100.0 % in non-severe group. On the 8th of April 2020, Wuhan city eased the lockdown policy after 76 days of the most restrict measurement ever. Herein, we collected 509 medical records from Leishenshan hospital to share some commonly interested COVID-19 clinical data.

A new type of highly infectious coronavirus, designated by 2019 new coronavirus (2019-nCoV), was firstly found in Wuhan, Hubei, China. Since the beginning of December, 2019, there reported some cases of viral pneumonia caused by unknown reasons, which attracted the focus of all over the world. Medical staff from all over the country began to station in there to survive those nearly collapse hospitals. We aim to compared with the mortality of the two studies from two different hospitals which directed by different management team including critical care medicine and respiratory critical care medicine in China.

The direct characterization of the spatial distribution of elements and compound binding of salt-organic associations in soil is imperative for understanding the mechanisms of organic matter decomposition and nutrient release in soil degradation and development processes. Modern spectroscopic techniques provide a feasible method for analysis at the microscale. In this study, mid-infrared attenuated total reflectance spectroscopy (FTIR–ATR) was used to obtain molecular functional group information, laser-induced breakdown spectroscopy (LIBS) was apply to obtain micro-level distribution features of elements in soil, and two-dimensional correlation spectroscopy (2DCOS) analysis was conducted to illustrate the binding combination features of mineral-organic associations in salinized from the Hetao Irrigation District in China. The results showed that the distributions of Mg, Ca, Na, and K were heterogeneous at the micro-level; the spatial distributions of Mg and Ca showed a significant correlation (r = 0.90***), while K displayed a negative correlation with the SOM contents. In soil with lower SOM contents, the elements were distributed at the top of the ablation area and enhanced with the increasing SOM content, which reflected the trends of the SOM layer thickness outside the mineral–organic associations at the micro-level. Furthermore, 2DCOS analysis suggested that the hydrogen bonds in silicate groups were stronger than those of organic functional groups, such as C=O/C=C, when combined with salt-related compounds, and Mg, Ca, Na, and K did not originate from clay mineral compounds in salinized soil, but partially originated from deposited organic associations.

Background Prematurity is a well-known risk factor for asthma. Biomarkers from sputum or serum were determined to have association with childhood asthma but no existing study has focused on salivary cytokines nor on prematurity. Thus, our study aimed to determine the relationship between childhood asthma and salivary cytokines in the early life of prematurity. Methods Preterm neonates from August 2012 to May 2017 were recruited and those with bacterial infection within seven days of life, maternal sepsis, and maternal clinical chorioamnionitis were excluded. Their gestational age, birth body weight, comorbidities, intubation duration, and infectious times during hospitalization were documented. The salivary cytokines on the first (D1) and seventh (D7) day of life were detected by MILLPLEX® MAP Human multiplex assay. They were followed up and divided into asthma and non-asthma groups. Kaplan-Meier or Cox-regression were used for analyzing the data. Results A total of 125 preterm infants were enrolled with 21 in the asthma group and 104 in the non-asthma group. Patients in the asthma group had longer duration of intubation (p < 0.001) and higher re-hospitalization rate for respiratory tract infection (p < 0.001), especially for respiratory syncytial virus bronchiolitis (p = 0.008). For salivary cytokines, the levels of D1 interleukin (IL)-8 were significantly higher in the asthma group (p = 0.04). Conclusions Salivary IL-8 at one day of life was associated with the development of asthma in childhood of premature neonates. Therefore, we can intervene early on these high-risk premature infants to prevent the occurrence of asthma.

Background: Mycoplasma pneumoniae pneumonia (MPP) is often complicated with co-infections that worsen the prognosis, but the outcomes in pediatric cases are unclear. The aim of this study is to investigate the association of co-infection and outcomes in severe MPP that occurs in childhood. Methods: This retrospective study included 184 pediatric cases of severe MPP that were managed at our hospital (between January 2014 and December 2017). The cohort was divided into the single Mycoplasma pneumoniae infection, co-infection with a noxa other than M. pneumoniae, and co-infection with two or more noxae other than M. pneumoniae groups. The demographic and clinical information of the patients was compared via statistical analysis. Results: The incidence of co-infections was high at 64.1%. Cytomegalovirus and Epstein-Barr virus were the most common causes of co-infection. According to the findings of binary logistic regression analysis, the presence of more than one pathogen (other than M. pneumoniae) was positively associated with the score determined from Pediatric Risk of Mortality III (β = 0.760, odds ratio [OR] = 2.139, 95% confidence interval [CI] = 1.391–2.390, P = 0.001), Pediatric Critical Illness Score (β = 1.203, OR = 3.328, 95% CI = 1.723–6.731, P = 0.000), and total length of hospital stay (β = 0.730, OR = 2.075, 95% CI = 1.404–3.066, P = 0.000). Conclusion: Viral and bacterial co-infection in pediatric cases of severe MPP is positively associated with hospitalization period and disease severity, and ultimately, may increase the chances of severe illness and death among children.

Tracheoesophageal fistula (TEF) with esophageal atresia (EA) is a common congenital anomaly that is associated with significant respiratory morbidity throughout life. The objective of this document is to provide a framework for the diagnosis and management of the respiratory complications that are associated with the condition. As there are no randomized controlled studies on the subject, a group of experts used a modification of the Rand Appropriateness Method to describe the various aspects of the condition in terms of their relative importance, and to rate the available diagnostic methods and therapeutic interventions on the basis of their appropriateness and necessity. Specific recommendations were formulated and reported as Level A, B, C based on whether they were based on “strong”, “moderate” or “weak” agreement. The tracheomalacia that exists in the site of the fistula was considered the main abnormality that predisposes to all other respiratory complications due to airway collapse and impaired clearance of secretions. Aspiration due to impaired airway protection reflexes is the main underlying contributing mechanism. Flexible bronchoscopy is the main diagnostic modality, aided by imaging modalities, especially CT scans of the chest. Non-invasive positive airway pressure support, surgical techniques such as tracheopexy and rarely tracheostomy are required for the management of severe tracheomalacia. Regular long-term follow-up by a multidisciplinary team was considered imperative. Specific templates outlining the elements of the clinical respiratory evaluation according to the patients’ age were also developed.

We performed an OCT-guided PCI to a 54 years old lady with NSTEMI. After a sirolimus-eluting BRS implantation, a second BRS was lost in the coronary artery. OCT helped us to implant the lost BRS together with two more drug-eluting stents. At 9-months follow-up OCT showed a good result.

Background In spite of high risk of mortality due to drug-induced QT interval prolongation (QTcP) usage among end stage renal disease patients (ESRD), no previous studies were conducted to assess medication safety of this drugs category among this vulnerable patients group. Objectives This study aimed to investigate the appropriateness and potential drug-drug interactions of QTcP-inducing drugs among ESRD patients in Jordan. Method This study was a cross-sectional retrospective study conducted in the outpatient clinics of 200 Jordanian healthcare facilities over three years (2017, 2018, and 2019) using Hakeem© database for data collection. CredibleMeds© was used to identify and categorise QTcP-inducing drugs. Drug-drug interactions and appropriateness of prescribing were assessed by Micromedex Drug Reax© software and a multidisciplinary committee, respectively. Results Of the 407 patients included, 954 drugs with risk of QTcP were dispensed; 618 (64.8%) had interactions with other drugs; 10.4% were major, 29.3% were moderate, and 60.3% were minor drug-drug interactions. Absence of major polypharmacy and co-morbidity decreased the odds of major drug-drug interactions by 61% (OR 0.61; 95% CI 0.23-0.97; p=0.02), and 72% (OR 0.72; 95% CI 0.44-1.23; p=0.04), respectively. After clinical evaluation, 17.6% of the dispensed drugs were considered inappropriate application, 12.9% were classified as inappropriate choice, and 26.4% were judged as inappropriate decision. Urology clinics were more likely to prescribe QTcP-inducing drugs based on inappropriate decision. Conclusion Major drug-drug interactions and dispensing medications with risk of QTcP based on inappropriate prescribing decisions for patients with ESRD were reported to be high in outpatient clinics in Jordan.

Background. Mood disorders are common in patients with cardiac implantable electronic devices (CIEDs). The lockdown related to COVID-19 pandemic may have further undermined their emotional well being exacerbating physical symptoms such as palpitations. We investigated the occurrence of anxiety and palpitations in CIEDs patients during the pandemic. In those with remote monitoring (RM) available, we evaluated whether these symptoms were associated with arrhythmic events. Methods and Results. The generalized anxiety disorder (GAD) 7-items questionnaire and the frequency of palpitations were assessed by telephonic interview in CIEDs patients Overall 152 CIEDs patients agreed to be interviewed (119 males, age 69±14 years). The RM was available in 54/152 (36%). Thirtyseven (24%) and 43 (28%) patients experienced anxiety and palpitations respectively, and 23 (15%) patients experienced both. Women were more likely to have symptoms than men (50% vs. 20%; p<0.01 for anxiety and 53% vs. 24%; p<0.01 for palpitations). Among patients with palpitations the RM was available in 17/43 (40%) and revealed the following arrhythmias in 7/17 (41%) patients: 8 non-sustained ventricular tachycardias (NSVT), 2 supra-ventricular tachycardias (SVT), 4 sustained ventricular tachycardias (VT). The RM enabled to detect in 6 patients a device malfunctioning: in 2 increased impedance in the shock lead, in 3 increased capture threshold for the LV lead and in 1 the battery reached the end of life Conclusion. Patients with CIEDs during the COVID19 outbreak were likely to experience anxiety and palpitations and the RM has been pivotal to ascertain the occurrence of arrhythmic events and device malfunctioning

Background: Management of pacemaker (PM) infections in patients with an advanced age is one of the most sensitive issues, since they possess particular clinical challenges due to higher rates of medical comorbidities. The novel leadless pacemaker (LP) requiring no transvenous lead or device pocket, may provide new opportunities for the management of PM infections among patients with an advanced age. Methods: We reviewed 8 octogenarians (median age of 86 [minimum 82 – maximum 90], male 63%) who received an LP implantation following a transvenous lead extraction (TLE) of an infectious PM. Results: All patients had more than 2 medical comorbidities. The indications for the LP implantations were atrioventricular block in 3 patients, atrial fibrillation bradycardia in 3, and sinus node dysfunction in 2. Five patients were bridged with a temporary pacing using an active fixation lead (median interval of 14.5 days), while one patient with severe dementia underwent a concomitant LP implantation and TLE during the same procedure. Successful TLEs and LP implantations were accomplished in all patients. There were no major or minor complications including vascular access troubles. All patients were discharged 2–8 days after the implantation. All patients stayed free of infection during the follow-up period of 6 months Conclusions: LP implantations were safe and effective after infected pacemaker removals in all 8 octogenarians. The novel LP technology may offer an alternative option in considering re-implantation of a PM even among patients with an advanced age and who are PM dependent.

Most common clinical manifestations of COVID-19 are fever, dry cough, dyspnea, fatigue, myalgia, sore throat, expectoration, hemoptysis, nausea, diarrhoea, abdominal pain and headache. But pleuritic chest pain as lone presenting symptom with COVID-19 is not reported till date.

Analysis of intra- and inter-population diversity has become important for defining the genetic status and distribution patterns of a species and a powerful tool for conservation programs, since high levels of inbreeding could lead into a whole population extinction in few generations. Microsatellites (SSR) are commonly used in population studies, but discovering highly variable regions across species’ genomes requires demanding computation and laboratorial optimization. In this work, we combine next generation sequencing (NGS) with automatic computing to develop a genomic-oriented tool for characterizing SSRs at the population level. Herein, we describe a new Python pipeline, named Micro-Primers, designed to identify and design PCR primers for amplification of SSR loci from a multi-individual enriched microsatellite library. The pipeline takes as input a fastq file containing sequences from NGS and returns a text file with information regarding the microsatellite markers, including number of alleles in the population, the melting temperature and the respective product of primer sets to easily guide the selection of optimal markers for the species. Experimental results show that Micro-Primers is able to reduce significantly a manual analysis that takes about 24 hours to 2 minutes, while keeping the same quality of the results.

Biodiversity studies greatly benefit from molecular tools, such as DNA metabarcoding, which provides an effective identification tool in biomonitoring and conservation programmes. The accuracy of species-level assignment, and consequent taxonomic coverage, relies on comprehensive DNA barcode reference libraries. The role of these libraries is to support species identification, but accidental errors in the generation of the barcodes may compromise their accuracy. Here we present an R-based application, BAGS (Barcode, Audit & Grade System), that performs automated auditing and annotation of cytochrome c oxidase subunit I (COI) sequences libraries, for a given taxonomic group of animals, available in the Barcode of Life Data System (BOLD). This is followed by implementing a qualitative ranking system that assigns one of five grades (A to E) to each species in the reference library, according to the attributes of the data and congruency of species names with sequences clustered in Barcode Index Numbers (BINs). Our ultimate goal is to allow researchers to obtain the most useful and reliable data, highlighting and segregating records according to their congruency. Different tests were performed to perceive its usefulness and limitations. BAGS fulfils a significant gap in the current landscape of DNA barcoding research tools by quickly screening reference libraries to gauge the congruence status of data and facilitate the triage of ambiguous data for posterior review. Thereby, BAGS have the potential to become a valuable addition in forthcoming DNA metabarcoding studies, in the long term contributing to globally improve the quality and reliability of the public reference libraries.

AbstractThe COVID-19 pandemic has had a profound impact on healthcare worldwide. Emergency presentations to hospital unrelated to COVID-19 have generally, significantly reduced. At our centre we have observed a substantial surge in the number of patients presenting with type A Aortic dissection (TAD). Despite having the warmest April on record, we have performed 8 TAD repairs, more than in any single month over the last decade. On histopathological examination there is no evidence of a direct link between the COVID-19 virus. We hypothesise that this surge relates to exacerbation of hypertension due to the substantial increase in mental health problems observed, associated with the pandemic and the ‘lock-down’ required to control the spread of the virus.During these unprecedented times we have seen a significant reduction in emergency medical attendance for non-COVID-19 associated illness. Despite this general trend, there has been a substantial increase in the incidence of acute type A aortic dissection (TAD) at our centre.We have performed 8 TAD repairs in April 2020. This is more than in any single month during the last decade. The mean number of TAD repairs in April over the previous 10 years was 2.1 (Table 1). Furthermore, several additional patients referred were transferred elsewhere due to our intensive care capacity.The seasonal variation in TAD incidence is well documented, with a significantly greater occurrence during winter, peaking in January as we observe in our own data (Table 1)1. The pathophysiological mechanism behind this is thought to be the influence of lower climatic temperatures raising arterial blood pressure through increased sympathetic activity exacerbating hypertension – one of the key aetiological factors for TAD1. In the UK, April 2020 has been the warmest since records began and from this, we would have expected a drop in the usual incidence of TAD for this time of year.A recent report has suggested an association between regional influenza activity and higher admission rates for TAD, although the pathophysiological explanation for this remains unclear and direct evidence of influenza in aortic tissue has not been previously examined in the context of aortic dissection2. Histopathological assessment of the resected aortas of patients in our series has not identified any evidence of an aortitis or suggestion of a direct link with COVID-19. Furthermore, none of our TAD patients have been symptomatic of COVID-19 at the time of presentation, nor had they history of having had the disease. They may, however, have been asymptomatic carriers.This surge in TAD may in fact be associated with increased psychological stress associated with the COVID-19 pandemic. The UK population has been subjected to a “lock-down” with social isolation since March 23rd. With the lock-down came increasing unemployment, potential financial difficulties and uncertainty together with an existential threat to life, which has undoubtedly caused a prolonged period of increased stress. As early as towards the end of March 2020 mental health experts warned of a “second pandemic” of acute stress disorders, post-traumatic stress disorder, emotional disturbance, sleep disorders, depressive syndromes and eventually suicides3. Indeed, this has become a reality. A review of the impact of COVID-19 on mental health in China, revealed an incidence of anxiety and depression in as many as 35% of survey respondents4.A recent report from New York has observed a 76.5% reduction in incidence of TAD during the pandemic5. However, they report a significant increase in ‘at-home’ deaths over this period and postulate that patients may be fearful of seeking medical attention during the pandemic and that there has actually not been a true decline in incidence of TAD. In sharp contrast to healthcare in the USA, the National Health Service in the UK is publicly funded, and this may well be responsible for our differing experiences of TAD presenting to hospital.It is widely recognised that stressful events can incite the development of a TAD by acute exacerbations of hypertension, and the prolonged state of heightened anxiety associated with the COVID-19 pandemic may have tipped the balance for many patients.At the same time, it has been reported that general practitioner appointments in the UK have fallen by at least 30% over this period. It is not difficult to see how a combination of increased mental stress and reduced health care provisions might lead to an increase of episodes of poorly controlled hypertension and subsequently in the incidence of TAD.We aim to highlight the increased incidence of this life-threatening disease during the current pandemic as a reminder to the medical community of this important, but often delayed, diagnosis.

This work investigates possible improvements in the accuracy of semiempirical quantum chemistry (SQC) methods for the prediction of standard enthalpy of formation (Δ_f H^o) through the use of artificial neural network (ANN) with molecular descriptors. A total number of 142 organic compounds with enough structural diversity has been considered in the training set. Standard enthalpy of formation for the selected compounds at the semiempirical PM3 and PM6 quantum chemistry methods is collected from literature, and is calculated by using semiempirical PM7 method in this work. The multiple stepwise regression is first employed to screen effective molecular descriptors, which are highly correlated with the error terms of the standard enthalpy of formation compared with experimental values. The obtained 7 effective molecular descriptors are then used as input set to establish three 7-11-1 neural network-based correction models to improve the accuracy of SQC methods. By using the developed correction models, the mean absolute errors (MAE) for Δ_f H^oof PM3, PM6, and PM7 methods are reduced from 22.36, 18.60, 17.27to 9.86, 9.83, 8.95, respectively in kJ/mol. Meanwhile, the results of the test set show that the neural network does not have the problem of over-fitting. Detailed analysis of the 7 effective molecular descriptors indicates that the major source to the correction models is from the electron withdrawing effect. The developed ANN models for the three selected SQC methods provide an efficient method for the quick and accurate prediction of thermodynamic properties.

The extent to which vector-borne diseases (VBDs) have shaped human history remains under-recognized, even in the disease ecology community, despite several well-known examples. Although they represent a significant threat to global human health, accounting for more than one billion cases and one million deaths annually, VBDs have coexisted with humans since the advent of civilization and have migrated with humans around the world. Here, we synthesize historical, anthropological, and archaeological evidence and examine it through an ecological lens to illustrate how four major VBDs—plague, malaria, yellow fever, and trypanosomiasis—have shaped the course of human history through three main pathways: (1) outcomes of colonialism, imperialism, war, and conflict; (2) human interactions with the environment; and (3) intrasocietal human interactions. For example, malaria tipped the American Revolution toward the Continental Army; plague promoted reforestation in Europe; yellow fever entrenched African slavery in colonies in the Americas; trypanosomiasis impeded large settlements and central governments in pre-colonial sub-Saharan Africa. By drawing comparisons across diseases, time periods, and geographic locations, we show how VBDs have historically affected human populations, from the age of early Homo sapiens to the modern context, and how they continue to impact the world.