An 83 year old female had asymptomatic SARS-CoV-2 infection while taking ruxolitinib. She remained RT-PCR positive for viral RNA for >120 days, Pegylated interferon for 4 weeks led to viral RNA clearance. The observations support combination therapy of ruxolitinib + interferon for COVID-19.

In this article we show the existence, uniqueness and Ulam stability results of the solution for a class of a nonlinear Caputo fractional integro-differential problem with mixed conditions. we use three fixed point theorems to proof the existence and uniqueness results. By the results obtained, the reasons for the Ulam stability are verified. An example proposed to illustrate our main results.

Germline mutations are the raw material for natural selection, driving species evolution and the creation of earth’s biodiversity. Life on earth would stagnate without this driver of genetic diversity. Yet, it is a double-edged sword. An excess of mutations can have devastating effects on fitness and population viability. It is therefore one of the great challenges of molecular ecology to determine the rate and spectrum by which these mutations accrue across the tree of life. Advances in high-throughput sequencing are providing new opportunities for characterizing these rates and patterns within species and populations, thus informing essential evolutionary parameters such as the timing of speciation events, the intricacies of historical demography, and the degree to which lineages are subject to the burdens of mutational load. Here, we will focus on the applications and limitations of whole-genome comparisons among closely related individuals in what are typically described as “trio” analyses for the detection of germline mutations as they arise in real time. By sequencing and comparing whole-genomes generated for individuals of known relatedness – typically, parent to offspring – investigators can ideally count and characterize mutations as they appear per generation. The promise for gaining insight into classic hypotheses of molecular evolution is high, though so too is the cost. Namely, the technical challenges are daunting given that pedigree-based studies are essentially searching for needles in a haystack. Even so, the opportunities are so enticing, and the field so young, we can say with confidence that fundamental insights have only just begun to emerge.

Carotenoid-based colours are a textbook example of honest signalling because carotenoids must be acquired from the environment. However, many species produce similar colours using self-synthesised pteridine pigments. A compelling but untested hypothesis is that pteridines compensate for low environmental availability of carotenoids because it is metabolically cheaper to synthesise pteridines than to acquire and sequester carotenoids. Based on a phylogenetic comparative analysis of 11 pigment concentrations in skin tissue of agamid lizards, we show that pteridine concentrations are higher and carotenoid concentrations lower in less productive environments. Both carotenoid and pteridine pigments were present in all species, but only pteridine concentrations explained colour variation among species. Furthermore, pigment concentrations were uncorrelated with indices of sexual selection. These results suggest that variation among species in pteridine synthesis compensates for environmental availability of carotenoids and challenge the paradigm of honest carotenoid signalling in vertebrates with complex colour production mechanisms.

Commentary:

Background and Purpose: Individualized assessment of the activity of cytochrome P450 2D6 (CYP2D6), a highly variable drug-metabolizing enzyme, is performed through phenotyping during which a probe drug is administered to measure the enzyme’s activity. In order to avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-invasive tools for real-time phenotyping of CYP2D6 could significantly contribute to the expansion of precision medicine in clinical practice. This study focuses on the identification of endogenous markers of the CYP2D6 enzyme in human biofluids using a liquid chromatography (LC)-high-resolution mass spectrometry (HRMS)-based metabolomics approach. Experimental Approach: Data from a control session were compared to data from an inhibition session. Before the latter, healthy volunteers (extensive and ultrarapid metabolizers) received a daily dose of paroxetine 20 mg over seven days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants. Key Results: In CYP2D6 extensive and ultrarapid metabolizers (n = 37), mean relative intensities of five features were significantly reduced during the inhibition session compared to the control session (fold changes ≤ 0.67, FDR-adjusted P < 0.0001). Furthermore, mean relative intensities of these candidates were significantly higher in the CYP2D6 extensive-ultrarapid metabolizer group (n = 37) compared to the poor metabolizer group (n = 6) (fold changes ≤ 0.67, P < 0.0001). Conclusion and Implications: The applied untargeted metabolomics strategy was able to identify five CYP2D6 endogenous metabolites, a promising discovery for non-invasive phenotyping and personalised medicine.

The pandemic caused by the novel coronavirus SARS-CoV2 has led to significant morbidity and mortality. Susceptibility to either contracting infection or presenting with symptoms has varied to a great extent among different populations. Whether specific occupations or lifestyles, other than the ones that predispose individuals to increased exposure, also play a role in shaping infection susceptibility is not yet fully understood. In India, due to a rich heritage of different classical dance genres, dance vocationally engages a great number of people. Moreover dance, being an aesthetic rendition of body movements, is established to have major influence of human health. With an aim to assess the susceptibility of SARS-CoV2 infection among the practitioner of various Indian classical dance genres, an internet-based survey was done based on a questionnaire. 6.04% of the dancers participating in the survey (N=182) reported past infection with SARS-CoV-2 virus confirmed by RT-PCR test, while 15.38% of them reported the same for one or more household members. The survey did not find any significant difference in age, body mass index between infected versus non-infected individuals. Further exploration of this occupational group with respect to COVID-19 disease outcomes as well as lung functions in health and disease are warranted.

Introduction Residual stone fragments remain a challenging topic for urologists following retrograde intrarenal surgery (RIRS). This study investigates the effectiveness of second-look flexible ureterorenoscopy (URS) to achieve a true stone-free status and decrease stone-related events. Material and Method A total of 176 consecutive patients treated with RIRS for kidney stones were included in the study. Patients were divided into two groups, group 1 receiving the standard of care (n=51) and group 2 receiving second-look flexible URS (n=125). In all cases, one or more calyceal stones of 1 to 4 mm were extracted with a basket at the time of stent removal. Unless earlier intervention was necessary, patients were followed up every six months to determine if they had experienced SREs. Results The mean follow-up time for the whole group was 21±11.1 months. The mean number of stones in group 1 and group 2 was 1.25±0.11 and 1.56±0.19, respectively. Postoperative stone-free rate after RIRS for group 1 and group 2 were 37.25% (n=19/51) and 40.8% (n=51/125), respectively. The SFR improved to 93.6% (n=117/125) in group 2. Multivariable analysis showed that type of intervention, stone size, and body mass index were independent prognostic factors for SREs. When group 2 was taken as a reference, the odds ratio for SREs was 8.48 (95% CI: 2.95–24.42) in group 1. Conclusion This study found that second-look flexible URS increased the SFRs and diminished the number of SREs. We propose performing second-look flexible URS following RIRS in the presence or suspicion of RSFs to provide better treatment results, less radiation exposure, and greater patient satisfaction. Key Words Retrograde Intrarenal Surgery, Flexible Ureteroscopy, Stone-free Rate, Residual stone Fragments, Stone-Related Event, Second-look Flexible Ureteroscopy.

Objective: To present an alternative surgical technique in treating cases of Chiari I Malformation with mild-to-moderate syringomyelia after decompressive suboccipital craniectomy: incising only the outer layer of the dura mater, then dissecting it from the inner layer without opening the latter. Methods and Results: We utilized this technique in a short series of three cases who were admitted in our department for mild symptoms such as intermittent headache and dissociated sensory loss in the upper limbs, caused by a Chiari Malformation Type I. The patients were placed in the sitting position. We performed a reduced median suboccipital craniectomy and resection of the posterior arch of C1 adapted to the level of tonsil descent, from a limited superior half to a complete resection. Afterwards, we incised the outer dural layer, while sparing the inner one. Using a fine dissector, we then split apart the outer and inner layers to the margin of the craniectomy. Through the transparency of the inner layer and the arachnoid, the cerebellum and the medulla were visible and pulsating. An autologous fascia duraplasty was then performed. The postoperative course was favorable in all cases, patients being discharged without any deficits and with complete symptom resolution. Conclusions: Interlayer dural split technique can be used effectively in treating symptomatic cases of type I Chiari malformation in adults, with mild-to-moderate syringomyelia. It is less invasive than opening the dura and possibly more effective than decompressive craniectomy and C1 laminectomy alone. This technique must be validated in a larger case-control series.

Ischemic mitral regurgitation (IMR) is a common complication, which is accompanied by myocardial infarction, causing heart failure and leading to poor prognosis. Although several surgical techniques have been reported, certain surgical methods have not been established for treating IMR. We report a successful case of left ventricular posterior wall plication through a left atriotomy over the mitral valve for IMR in a patient who experienced cardiac shock and could not be weaned off mechanical support. Posterior wall plication changed the left ventricle from a spherical to an oval shape, restored the position of papillary muscles and posterior wall, improved leaflet tethering, and prevented further remodeling of the left ventricle. This method may be useful for treating IMR and improve patients’ prognosis.

Background: Muscle wasting and limitation in physical activity have been reported in patients with hemodialysis; this leads to poor quality of life at the end. Objective: To develop the respiratory training device and to determine the efficiency of the prototype on respiratory muscle strength, functional capacity and dyspnea perception in hemodialysis patients. Design, setting and participants: the development of respiratory device was created and then effects of respiratory device were examined in hemodialysis patients. A total of 25 patients with quasi experimental study was recruited in the present study with aged ≥ 35 years old. All participants had a history of hemodialysis 3 days per week. Outcome measurements and statistical analysis: The protocol was conducted 15 inhales, three set per day with 40% of maximal inspiratory pressure; totally 45 inhales. The participants were asked to perform for three times per week during on hemodialysis. Respiratory muscle strength, the 6minute walk test and rate of dyspnea scores were assessed before and after 8-week intervention program. Paired t-tests was used to compare between initial values and follow-up values in respiratory prototype. Results: Of 25 patients at initially was enrolled, 22 individuals (88%) completed in the 8-week program. Significant improve in inspiratory muscle strength, 6minite walk distance and rate of dyspnea was observed after 8-week intervention (12.44± 3.55 cmH2O, 24.78 ± 8.89 meters, and 0.50 ± 0.19, respectively). Conclusion: Using porotype of respiratory device can effectively improve cardiorespiratory performance which is marked by increasing inspiratory muscle functional capacity and rate of dyspnea in hemodialysis patients after 8-week training program.

Objective: This study aimed to investigate the association between carotid intima-media changes that play a part in the atherosclerotic process in childhood obesity and fibrin monomers as an important indicator of fibrin plaque. Methods: This is a cross-sectional study of obese children and non-obese healthy control subjects. Height, weight, body mass index, waist/hip ratio, systolic/diastolic blood pressures were recorded, in addition, biochemistry, hemogram, fibrin monomers and d-dimer were measured in both groups. Right and left common carotid intima-media thicknesses were measured by ultrasonography and mean carotid intima-media thickness was calculated. Results: Obese children (n=89, 46.1% girls, median age: 12.6±2.3 years) and healthy control group (n=40, 52.5% girls, median age: 13.2±2.2 years) were comparable in terms of gender, age and puberty stage. Mean carotid intima-media thickness was higher in obese children than the healthy control group (p=0.002). There was no difference between the two groups in terms of fibrin monomers and D-dimer levels. In obese children, there was a weak negative correlation between mean carotid intima-media thickness and fibrin monomers (p=0.030, r=-0.233). Conclusion: In obese children, mean carotid intima-media thickness was determined higher, as an early indicator of atherosclerosis. We want to emphasize that obese children are at risk for cardiovascular disease and should be evaluated in terms of atherosclerosis. This study investigates the relation between increased carotid intima-media thickness and fibrin monomers, in children, the first time in Literature. What’s already known about this topic? It is possible to reveal the early period of the atherosclerosis process by showing carotid intima medial thickness. Fibrin is a major component of many atherosclerotic plaques. What does this article add? Our study investigated the relationship between mean carotid intima-media thickness in childhood obesity and fibrin monomers. But no positive correlation was found between fibrin monomers and the carotid intima-media thickness.

Failure in the prevention of cross-transmission from contaminated gloves has been recognized as an important factor that contributes to the spread of several healthcare-associated infections. Ex situ coating process with silver nanoparticles (AgNPs) using Eucalyptus citriodora ethanolic leaf extract as reducing and capping agents to coat glove surfaces has been developed to prevent this mode of transmission. Elemental analysis of coated gloves showed 24.8 Wt% silver densely adhere on the glove surface. The coated gloves fully eradicated important hospital-acquired pathogens including Gram-positive bacteria, Gram-negative bacteria, and yeasts within 1 h. The coated gloves showed significant reduction, an average of 5 logs when tested against all standard strains and most clinical isolates (p < 0.01). Following prolonged exposure, the coating significantly reduced the numbers of most adhered pathogenic species, compared with uncoated gloves (p < 0.0001), which was observed by fluorescence microscopy. Scanning electron microscopy further confirmed that AgNPs coated-gloves reduced microbial adhesion of mixed-species biofilms, compared with uncoated gloves. A series of contamination and transmission assays demonstrated no transmission of viable organisms. Biocompatibility analysis confirmed high cell viability of HaCaT and L929 cells at all concentrations of AgNPs tested. The coated gloves were non-toxic with direct contact with L929 cells.

The Sabatier process is promising for carbon dioxide utilization and energy storage. However, the serious problem that limits more comprehensive industrial applications is catalyst deactivation due to the temperature runaway phenomenon. The inert particle dilution approach, including the mixing dilution method and layered dilution method is applied to solve this problem. Based on the lattice kinetic scheme-lattice Boltzmann method (LKS-LBM), the effects of three parameters in bed dilution structure reconstructed by the discrete element method (DEM) on temperature distribution and carbon conversion rate were discussed, so as to investigate the relationship between packing structure and temperature distribution. Furthermore, numerical results indicated that an optimal bed dilution structure, which not only can control the peak temperature below the critical temperature to avoid coking and sintering of catalyst, but also can improve the carbon conversion rate by almost 18% compared with the structure without dilution under the same circumstance.

One Electrogram-Tracing Tells All: what is the mechanism of this supraventricular tachycardia?Moyuru Hirata, MD*, Yuji Wakamatsu, MD*, Koichi Nagashima, MD, PhD*, Sayaka Kurokawa, MD, PhD*, Naoto Otsuka, MD*, Seina Yagyu, MD*, Shu Hirata, MD*, Toshiko Nakai, MD, PhD*, Yasuo Okumura, MD, PhD*.*Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondenceKoichi Nagashima, MD, PhD; Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, JapanTel: +81-3-3972-8111Fax: +81-3-3972-1098E-mail: cocakochan@gmail.comTotal word count: 1036 words, 2 FiguresFunding: (None)Disclosures: (None)The work described was supported by departmental resources only.Keywords: narrow QRS tachycardia, atrioventricular nodal reentrant tachycardia, accessary pathway.

Background The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies aimed to evaluate if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Methods Two randomized double-blind placebo-controlled trials of ILIT for grass pollen induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10 000 SQ-U with one month in between was evaluated. Results ILIT in doses up to 10 000 SQ-U was safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS, quality of life and nasal provocation response. Flow cytometry analyses could not detect any T-cell changes, while lymph node derived dendritic cells showed increased activation. Conclusion ILIT in high doses after SCIT appears to further reduce grass pollen induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3 000 SQ-U should be avoided.

A 71-year-old asymptomatic man was brought to our emergency department for ingesting a removable partial denture. The plain cervical computed tomography showed that the denture was in the hypopharynx. Transoral retrieval of the denture, with the clasp detached from the cervical esophagus, using laryngoscope-guided forceps under local anesthesia.

The diagnosis of acute myocarditis (AM) remains challenging because of its diverse clinical manifestations. Thus, a wide range of diagnostic tests may be warranted. Although cardiac magnetic resonance (CMR) is the preferred imaging technique, it may not be applicable in the acute AM phase. Our case report highlights the usefulness and diagnostic accuracy of echocardiographic examination. In the first 2-dimensional echocardiography, the focal echobright was presented. A reduced value of global longitudinal strain, and regional disturbances of segmental myocardial strain, both longitudinal and circumferential, in the epicardial layer, were detected with a good correlation with CMR results.

Managing endangered species in fragmented landscapes requires estimating dispersal rates between populations over contemporary timescales. Here we develop a new method for quantifying recent dispersal using genetic pedigree data for close and distant kin. Specifically, we describe an approach that infers missing shared ancestors between pairs of kin in habitat patches across a fragmented landscape. We then apply a stepping-stone model to assign unsampled individuals in the pedigree to probable locations based on minimizing the number of movements required to produce the observed locations in sampled kin pairs. Finally, we use all pairs of reconstructed parent-offspring sets to estimate dispersal rates between habitat patches under a Bayesian model. Our approach measures connectivity over the timescale represented by the small number of generations contained within the pedigree and so is appropriate for estimating the impacts of recent habitat changes due to human activity. We used our method to estimate recent movement between newly discovered populations of threatened Eastern Massasauga Rattlesnakes (Sistrurus catenatus) using data from 2996 RAD-based genetic loci. Our pedigree analyses found no evidence for contemporary connectivity between five genetic groups, but, as validation of our approach, showed high dispersal rates between sample sites within a single genetic cluster. We conclude that these five genetic clusters of Eastern Massasauga Rattlesnakes have small numbers of resident snakes and are demographically isolated conservation units. More broadly, our methodology can be widely applied to determine contemporary connectivity rates, independent of bias from shared genetic similarity due to ancestry that impacts other approaches.

Background and objective: The number of children with complex physical and developmental pathologies, including chronic respiratory insufficiency, surviving and growing beyond early childhood continues to rise. No study has examined the clinical pathway of children on invasive LTMV in an Irish setting. Our data over a 10-year period was reviewed to see if our demographics and outcomes are in line with global trends. Methods: Children’s Health Ireland (CHI) at Crumlin, Dublin is Ireland’s largest tertiary paediatric hospital. A retrospective review analysed data from children in our centre commenced on LTMV via a tracheostomy over 10 years (2009 – 2018). This data was subdivided into two epochs for statistical analysis of longitudinal trends. Results: Forty-six children were commenced on LTMV from 2009 to 2018. Many had complex medical diagnoses with associated co-morbidities. Far less children, 30.4% (n=14) commenced on LTMV in the latter half of the 10-year period, they also fared better in all aspects of their treatment course. Focusing solely on children who have needed LTMV over this timeframe has enabled us to isolate trends specific to this cohort. Less patients commenced LTMV on a year on year basis, and for those that require tracheostomy and LTMV, their journey to decannulation tends to be shorter. Conclusion: Over the period reviewed, less patients over time necessitated long-term invasive therapy and those patients are being weaned and decannulated with ever more success. This has implications in terms of predicting numbers transitioning to adult services and allocation of hospital and community care resources.

Generalized Linear Model (glm) has been widely used in regression models. Iteratively weighted least squares algorithm (IWLS) and coordinate descent (CD) algorithm are technique that can used to nd maximum likelihood function for generalized linear model. We are interested in comparing the two algorithm to the framework of regression models with binary responses. Link function is an important component in the generalized linear model. We carried out a simulation study to compare glm using IWLS algorithm and CD algorithm performance under dierent link functions. The link functions we investigated include the commonly used logistic (logit), probit and complementary log-log links (cloglog). We also wrote an algorithm glm using iteratively weighted least squares and coordinate descent algorithm. Our results show that under IWLS algorithm perform better than glm under CD algorithm when we increase the number of variable. The current study helps our future research to build an integrated process of variable selection via lasso along with a exible link function.

1. Stable isotopes represent a unique approach to provide insights into the ecology of organisms. δ13C and δ15N have specifically be used to obtain information on the trophic ecology and food web interactions. The trophic discrimination factor (TDF, Δ13C and Δ15N) describes the isotopic fractionation occurring from diet to consumer tissue and this value is critical to obtain precise estimates within any application of δ13C and δ15N. It is widely acknowledged that metabolism influences the TDF, being responsible for different TDFs between tissues of variable metabolic activity (e.g. liver vs. muscle tissue) or species body size (small vs. large). However, the connection between the variation of metabolism occurring within a single species during its ontogeny and TDFs has rarely been considered. 2. Here, we conducted a 9-month feeding experiment to report Δ13C and Δ15N of muscle and liver tissue for several weight classes of Eurasian perch (Perca fluviatilis), a widespread teleost often studied using stable isotopes, but without established TDFs for feeding on a natural diet. In addition, we assessed the relationship between the standard metabolic rate (SMR) and TDFs by measuring their oxygen consumption of the individuals. 3. Our results showed a significant negative relationship of SMR with Δ13C, but not with Δ15N of muscle or TDFs of liver tissue. SMR was significantly higher in perch juveniles, which translated to significantly lower Δ13C of muscle tissue. 4. In summary, our results emphasize the role of metabolism in shaping specific TDFs (i.e. Δ13C of muscle tissue), and especially highlight the substantial differences between individuals of different ontogenetic stages within a species. Our findings thus have direct implications for the use of stable isotope data and the applications of stable isotopes in food web studies.

Objectives: The goal of this study was to describe and evaluate our simulation training program on biological models for the cardiovascular surgery residency program at our institution. Material and Methods: Since 2016, with the purpose to develop better practical performance and evaluate the improvement of resident’s surgical skills, it was implemented a simulation training program, composed of some elemental procedures in cardiovascular surgery. It was established one wet lab session weekly lasting 2 hours, coached by 2 expert cardiovascular surgeons. Bovine and porcine hearts were used as biological models. At the end of the hands on program, an objective assessment consisting of 2 practical modules was applied and performance was rated by way of a 5-point scale. In addition, to provide a subjective assessment, each resident filled out a questionnaire consisting of 3 items reviewing the overall quality of the workshops on a 10-point scale. Results: The objective evaluation applied at the end of the training program consisted by valve replacement and coronary artery bypass grafting (CABG) modules. The mean performance rating scores for valve replacement module ranged from 4.2 to 4.79, and to CABG, from 4.33 to 4.87. Regarding subjective assessment, all items evaluated, such as expert’s didactics, simulation performance and biological simulator fidelity, received high grades (above 9 on a 10-point scale). Conclusions: Simulator training on biological models for cardiac surgery medical residents is a simple and effective learning method of surgical skills.

In this issue, Zhao et al. investigate the effects of subclinical hypothyroidism in coronary bypass grafting particularly with respect to the incidence of atrial fibrillation. While not the first of its kind, the authors analyze this controversial topic in a well powered, statistically comprehensive manner that furthers our understanding of the effects of SCH in CABG patients.