Managing women who are pregnant with severe COVID-19 is complex. This paper focuses on the debate surrounding steroid use in this group. Unfortunately, despite international efforts to identify treatments for COVID-19, there is very little research which has focussed specifically on pregnant women. Therefore current guidance is based on consensus and expert opinion, with variation in these guidelines worldwide, and reports that 73% of pregnant women do not receive steroids at all. There is an assumption of a steroid class-effect implicit within the UK guidelines for the mother with COVID-19 which is at odds with established within-class differences for effects on the foetus. This now warrants further discussion given the increasing numbers of pregnant women being admitted to hospital with COVID-19.  

A recent study on the Taylor series method of second order and the trapezoidal rule for dynamic equations on time scales has been continued by introducing a derivation of the Taylor series method of arbitrary order $p$ on time scales. The error and convergence analysis of the method is also obtained. The 2 step Adams-Bashforth method for dynamic equations on time scales is concluded and applied to examples of initial value problems for nonlinear dynamic equations. Numerical results are presented and discussed.

Aspirin is one of the most widely used medicines in the world and has been on the market for over a century. Therefore, it is surprising that little solid research has been done regarding the effects of aspirin on the liver. If anything, you can find a few studies from the 1970s. At that time, aspirin was described as damaging to the liver by quite some authors. But since the turn of the millennium, studies have suddenly appeared that attribute a liver-protective effect to aspirin. We have investigated this contradiction and found a tipping point effect of high clinical relevance.

Both surface motion and hole stress concentration have always been concerned in anisotropic medium. In this paper, a theoretical approach is used to study the scattering problem of circular holes under a scalene trapezoid on the surface. The mapping function that anisotropic medium to homogeneous medium is established, and the relationship between the free boundary of anisotropic medium and the mapping of homogeneous medium boundary is proved. In the space of homogeneous medium mapping, the wave displacement function is obtained by solving the equation of motion that meets the zero-stress boundary conditions by separating the variable method and the symmetric method. Based on the complex function, multi-polar coordinate method and region-matching technique, algebraic equations are established at auxiliary boundary and free boundary conditions in complex domain. Then according to sample statistics, least square method is used instead of the Fourier expansion method to solve the undetermined coefficient of the algebraic equations by discrete boundary. Numerical results shows that the continuity of the auxiliary boundary and the accuracy of the zero-stress boundary are nice, and the displacement of the free surface and the stress of the circular hole are related to the parameters of material medium, the position of the circular hole, the direction of the incident wave and the frequency content of the excitation. Finally the process of the wave propagation and scattering around trapezoid and shallow circle are shown in time domain through the inverse fourier transform.

Sexual Minority Individuals and Pregnancy Outcomes: A CommentaryJulie Croll, MPHa,b; Laura Sanapo, MD, MSHS, RDMSa,c; Ghada Bourjeily, MD, FCCPa,caWomen’s Medicine Collaborative at Lifespan, The Miriam Hospital, 146 West River Street, Providence, RI 02904, USAbRCSI University of Medicine and Health Sciences, School of Medicine, 123 St Stephen’s Green, Dublin 2, IrelandcWarren Alpert Medical School of Brown University, Department of Medicine, 222 Richmond Street, Providence, RI, USA

Merck's Molnupiravir is a global catastrophic risk. Its broad use as a treatment for COVID-19 will create dangerous variants of SARS-COV-2. It is already in use in some countries. Molnupiravir ("MOLN"), a presumed anti-COVID19 drug, acts by significantly increasing the RNA error rate in the coronavirus replication. That exponentially increases the probability of many mutations in a single copy. Copies containing a large set of new mutations are disproportionately likely to create dangerous mutations. Patients taking MOLN are expected to carry and shed the virus in almost equal volumes as untreated patients. Estimates show that MOLN would increase the frequency of sets of 8 mutations by 3,000 times, and sets of 12 mutations by 240,000 times, per virus generation, per person. This does not include recombinations and many other effects which are likely to compound these results. Multiple rounds of replication and natural selection per person further increase the threat. The impact cannot be detected immediately due to a possible lag between the appearance of a new variant and the necessary changes in external conditions, which lead to its spread. At least some of the many artificial variants, induced by the MOLN treatment, are likely to combine immune escape, higher contagiousness, and higher virulence, just to mention a few. This would be a gain-of-function experiment, performed on the entire human race.

A document by PAOLA TOAPANTA-PINTA, written on Authorea.

Introduction: Since the first COVID-19 cases were reported, the disease's clinical and epidemiological characteristics have continuously been studied, although they have not been yet defined. Objective: To estimate the epidemiological profile of pediatric patients with COVID-19, as well as their clinical, laboratory and radiological characteristics. Materials and methods: A living systemic review was conducted in the PubMed, Scopus and SciELO databases. Observational studies describing clinical, radiological, and laboratory characteristics of pediatric patients with COVID-considered for the search; there were no language restrictions. Government, epidemiological, and pre-print papers were also considered. Meta-analyses of single proportion (frequentist approach) and two proportions (Bayesian method) were carried out. The study registration and protocol are available at https://osf.io/y43wm and https://osf.io/r8ktv, respectively. Results: 13 studies, with a total of 9 152 patients, were retrieved. The Bayesian meta-analysis reported that males are more affected by the disease: OR 1.24 (HDI95%: 1.09-1.4). The proportion results calculated by means of the frequentist meta-analysis are: 52% cough (95%CI: 50-55), 0% death (95%CI: 0-0.1), 16% high aspartate transaminase levels (95%CI: 13-19), and 60% lung changes observed in chest X-ray (95%CI: 57-64). Conclusions: Based on the current data, it is not possible to describe accurately the clinical and epidemiological characteristics of COVID-19 in the pediatric population. However, evidence suggests that males are more affected by the disease and that lung alterations in imaging studies are more frequent than clinical signs such as cough and fever. Laboratory test results are not conclusive and show that different organs and systems of the human body may be affected by SARS-CoV-2. The results reported here must be compared to prospective controlled studies conducted in larger samples and a more rigorous design.

This realist enquiry applying behavioural theory aimed to identify behavioural mechanisms and contexts that facilitate prescribers tapering opioids. We identified relevant opioid tapering interventions and services from a 2018 international systematic review and a 2019 England-wide survey, respectively. Interventions and services were eligible if they provided information about contexts and/or behavioural mechanisms influencing opioid tapering success. A stakeholder group (n=23) generated draft programme theories based around the 14 domains of the theoretical domains framework. We refined these using the trial and service data. From 71 articles and 21 survey responses, 56 and 16 respectively were included, representing primary care, hospital, specialist pain facilities and prison services. We identified six programme theories that included five behavioural mechanisms: prescribers’ knowledge about how to taper; build prescribers’ beliefs about capabilities to initiate tapering discussions and manage psychological consequences of tapering; perceived professional role in tapering; the environmental context enabling referral to specialists; and facilitating positive social influence by aligning patient: prescriber expectations of tapering. No interventions are addressing all six mechanisms supportive of tapering. Work is required to operationalise programme theories according to organisational structures and resources. An example operationalisation is combining tapering guidelines with information about local excess opioid problems and endorsing these with organisational branding. Prescribers being given the skills and confidence to initiate tapering discussions by training them in cognitive-based interventions and incorporating access to psychological and physical support in the patient pathway. Patients being provided with leaflets about the tapering process and informed about the patient pathway.

Background/Purpose: Systemic sclerosis (SSc) is characterised by progressive multiple-organ fibrosis leading to morbidity and mortality. Lysyl oxidases play a vital role in the cross-linking of collagens and subsequent build-up of fibrosis in the extracellular matrix. As such, their inhibition provides a novel treatment paradigm for SSc. Experimental Approach: Lysyl oxidases are upregulated in preclinical models of fibrosis in skin, lung, heart, kidney and liver. A novel small molecule pan-lysyl oxidase inhibitor, PXS-5505, currently in clinical development for bone fibrosis treatment was evaluated in in vivo rodent models resembling the fibrotic conditions in SSc. Key Results: Both lysyl oxidase and lysyl oxidase-like 2 (LOXL2) expression was elevated in the skin and lung of SSc patients. Once-a-day oral application of PXS-5505 inhibited lysyl oxidase activity in the skin and LOXL2 activity in the lung. PXS-5505 exhibited anti-fibrotic effects in the SSc skin mouse model, reducing dermal thickness and α-smooth muscle actin compared to the disease controls. Similarly, in the bleomycin-induced mouse lung model, PXS-5505 reduced tissue fibrosis toward normal levels. The anti-fibrotic efficacy of PXS-5505 in the bleomycin exposed lungs was mediated by its ability to normalise collagen/elastin crosslink formation, a direct consequence of lysyl oxidase inhibition. PXS-5505 also reduced area of fibrosis in rodent models of the ischaemia-reperfusion heart, the unilateral ureteral obstruction kidney and the CCl4-induced fibrotic liver. Conclusion/Implication: PXS-5505 consistently demonstrates potent anti-fibrotic efficacy in multiple models of organ fibrosis relevant to the pathogenesis of SSc, suggesting that it may be efficacious as a novel approach for treating SSc.

Studies on physiological effects due to gravitation and acceleration have become a hot topic of research since the last century. Scientists and engineers have been putting their best efforts to excavate more about the physiological changes that occur in jet aircraft pilots and astronauts. This study focuses on a few prominent and recent observations related to the alterations of physiological functioning due to gravitational and acceleration forces.

Classic Congenital Adrenal Hyperplasia in males usually presents late until before puberty, but rarely at birth. In cases of undiagnosed CAH, severe deficiency of cortisol may lead to life threatening situation in an infant with acute salt losing crisis. Screening for CAH at birth can lead to better outcomes.

Coronavirus disease 2019 (COVID-19) is an emerged pandemic disease caused by a new coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2).

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease caused by a combination of prenatal and postnatal factors that leads to the disruption of lung development and abnormal repair, this is a condition that is commonly seen in premature infants. With the improvement of treatment technology, the survival rate of very early preterm infants has increased significantly compared with before, and the incidence of severe BPD has decreased, however, the prevalence of BPD has not decreased. The overall prevalence of BPD is 45%.The prevention of prematurity, the systematic use of non-aggressive ventilator measures, the avoidance of supra-physiological oxygen exposure, and the administration of diuretics, caffeine and vitamin A have all been shown to lead to a significant reduction in the risk of BPD development. A growing number of clinical studies have shown that caffeine not only prevents apnea, but also reduces the incidence of BPD. We review the clinical value of caffeine in the treatment of BPD and its potential mechanisms of action, include anti-inflammatory, antioxidant, anti-fibrotic, anti-apoptotic pathways, and the regulation of angiogenesis. Our aim was to provide a new theoretical basis for the clinical treatment of BPD.

A 59-year-old man with a long smoking history presented with sudden back pain. Frank's sign was noticed in his bilateral ears, and computed tomography revealed Stanford type A acute aortic dissection. If young patients have Frank's sign, attention should be paid to atherosclerotic disease including aortic disease.

1. Competition from invasive species is an increasing threat to biodiversity. In Southern California, the western gray squirrel (Sciurus griseus, WGS) is facing increasing competition from the fox squirrel (Sciurus niger, FS), an invasive congener. 2. We used spectral methods to analyze 140 consecutive monthly censuses of WGS and FS within a 11.3 ha section of the California Botanic Garden. Variation in the numbers for both species and their synchrony was distributed across long timescales (> 15 months). 3. After filtering out annual changes, concurrent mean monthly temperatures from nearby Ontario Airport (ONT) yielded a spectrum with a large semiannual peak and significant spectral power at long timescales (> 30 months). Squirrel-temperature cospectra showed significant negative covariation at long timescales (> 35 months) for WGS and smaller significant negative peaks at 6 months for both species. 4. Simulations from a Lotka-Volterra model of two competing species indicates that the risk of extinction for the weaker competitor increases quickly as environmental noise shifts from short to long timescales. 5. We analyzed the timescales of fluctuations in detrended mean annual temperatures for the time period 1915-2014 from 1218 locations across the continental USA. In the last two decades, significant shifts from short timescales to long timescales have occurred, changing from less than 3 years to 4-6 years. 6. Our results indicate that (i) population fluctuations in co-occurring native and invasive tree squirrels are synchronous, occur over long timescales, and may be driven by fluctuations in environmental conditions; (ii) long timescale population fluctuations increase the risk of extinction in competing species, especially for the inferior competitor; and (iii) the timescales of interannual environmental fluctuations may be increasing from recent historical values. These results have broad implications for the impact of climate change on the maintenance of biodiversity.

We report a preterm male neonate presenting with a skeletal dysplasia associated with multiple congenital anomalies. Radiologic findings and genetic studies are consistent with spondylocostal dysostosis (SCD) and autosomal dominant brachydactyly. This is the first case report of spondylocostal dysostosis and brachydactyly associated with TBX6 and IHH variants.

This report describes a case of a 50-year-old man with hypertension who was admitted with a history of fever, chills, and shortness of breath and tested positive for COVID-19. Shortly after resolving his ARDS, he developed an adipsic hypernatremia with associated confusion, lethargy, and weakness.

The COVID-19 vaccination programs have sparked several concerns and ongoing debates over safety issues. Here, we presented three cases of patients with serious adverse events, encephalopathy; Vaccine induced thrombotic thrombocytopenia, and Leukocytoclastic Vasculitis, after receiving the ChAdOx1 nCoV-19 vaccine.

Our case was rare in that multiple phenomena of postpartum stroke occurred at the same time. What is remarkable about this case was the confirmation of the reversibility of these pathological conditions through multifaceted evaluations, including the MRI MSDE method.

Storing and manipulating Next Generation Sequencing (NGS) file formats for understanding biological phenomena is an essential but difficult task in the life sciences. Yet, most methods for analysing NGS data require complex command-line tools in high-performance computing (HPC) or web-based servers and have not yet been implemented in comprehensive, easy-to-use software. Here we present easyfm (easy file manipulation), a free standalone Graphical User Interface (GUI) software with Python support that can be used to facilitate the rapid discovery of target sequences (or user’s interest) in NGS datasets for novice users (more accessible to biologists). It enables them to perform end-to-end reproducible data analyses using a desktop application (Windows, Mac and Linux). Unlike existing tools, the GUI-based easyfm is not dependent on any HPC system and can be operated without an internet connection. For user-friendliness and convenience, easyfm was developed with four work modules and a secondary GUI window, covering different aspects of NGS data analysis, including post-processing, filtering, format conversion, generating results, real-time log, and help. In combination with the executable tools (BLAST+ and BLAT) and Python, easyfm allows the user to set analysis parameters, select/extract regions of interest, examine the input and output results, and convert to a wide range of file formats. To help augment the functionality of existing web-based and command-line tools, easyfm, a self-contained program, comes with extensive documentation (https://github.com/TaekAndBrendan/easyfm). This specific benefit allows easyfm to seamlessly integrate visual and interactive representations of NGS files, supporting a wider scope of bioinformatics applications in the life sciences.

237 RESUMEN El peso del recién nacido es resultado de su crecimiento intrauterino. Se identifican los factores de riesgo perinatales asociados a bajo peso al nacer en neonatos nacidos en el Hospital Gineco obstétrico Isidro Ayora, Quito, Ecuador, internados entre enero 2010 y diciembre 2015. La fuente de datos fue el Sistema Informático Perinatal y se realizo un estudio retrospectivo, observacional, descriptivo y analítico en el cuyos datos se analizaron la prueba de Chi y Odds Ratio con su intervalo de confianza al 95%. Las variables significativamente asociadas al bajo peso al nacer fueron: madres con multiples gestas previas, consumidoras de drogas, afectaciones hipertensivas crónicas, preeclámpsia severa y eclampsia, nefropatía cronicas, embarazo múltiple, restricción del crecimiento intrauterino, escasas consultas prenatales, sexo femenino y prematurez. Se detectaron factores de riesgo significativamente asociados al bajo peso al nacer. PALABRAS CLAVE: Peso bajo al nacimiento. Embarazo multiple. Trastornos hipertensivos del embarazo. ABSTRACT Newborn birth weight is the result of its intrauterine growth. It is variable according to gestacional age, or presence of several risk factors. A survey was performed in order to identify perinatal risk factors associated with low birth weight < 2500 g. at the Isidro Ayora Maternity Hospital, Quito, Ecuador, January 2010 until December 2015. The data source was the Perinatal Information System (SIP). The trial was retrospective, observational, descriptive and analytical. Chi2 test, Odds Ratio, 95 % confidence interval were considered in the study. The main variables associated to low birth weight were mothers with several previous pregnancies, drug consumers, chronic hypertensive disorders patients, eclamptic, chronic nephropathy, multiple pregnancy, intrauterine growth restriction, inadequate prenatal care, female and premature babies. Main risk factors significantly associated with low birth weight were identified. KEY WORDS: Low birth weight. Multiple Gestation. Chronic hypertensive disorders INTRODUCIÓN El Bajo Peso al Nacer (BPN), ha sido definido por la Organización Mundial de la Salud (OMS) como el peso al nacer menor de 2500 gramos. La tasa de BPN es considerada un indicador trascendente de la salud pública y es un problema mundial que impacta en gran medida sobre la mortalidad neonatal e infantil[1]. En América representa el 8,5% y en Ecuador el 8,4%, por lo que es uno de los países que presenta la menor incidencia de BPN en la región[2]. El peso corporal de cada recién nacido (RN) es el resultado de su crecimiento intrauterino desde la concepción hasta el parto. Es variable según su edad gestacional (EG), su potencial genético y la presencia o ausencia de factores que pueden provocar desviación de la normalidad[3]. La frecuente utilización del PN en el campo socio-sanitario es atribuible a que: a) Expresa el resultado final de las condiciones del embarazo; b) Su registro como parte de las estadísticas vitales es cuidadoso; c) Constituye un poderoso predictor de la sobrevida individual del recién nacido un predictor poblacional de mortalidad infantil; d) Ha Factores de riesgo para bajo peso al nacer ARTÍCULO ORIGINAL Factores de riesgo para bajo peso al nacer.

This is a case of a 16-year-old African boy with Osteomyelitis presenting with symptoms of reactive arthritis (Reiter’s syndrome) KEYWORDS Osteomyelitis, Reiter’s syndrome, Fever, Bone pain, Erythema, Ewing sarcoma

The combined study of C and O isotopes in plant organic matter has emerged as a powerful tool for understanding plant functional response to environmental change. The approach relies on established relationships between leaf gas exchange and isotopic fractionation to derive a series of model scenarios that can be used to draw inferences about changes in photosynthetic assimi-lation and stomatal conductance driven by changes in environmental parameters (CO2, water availability, air humidity, temperature, nutrients). We review the mechanistic basis for model and research to date, and discuss where isotopic observations don’t match our current under-standing of plant physiological response to environment. We demonstrate that 1) the model has been applied successfully in many, but not all studies, and 2), while originally conceived for leaf isotopes, the model has been applied extensively to tree ring isotopes in the context of tree phys-iology and dendrochronology. Where isotopic observations deviate from physiologically plau-sible conclusions, this mismatch between gas-exchange and isotope response provides valuable insights on underlying physiological processes. Overall, we found that isotope responses can be grouped into situations of increasing resource limitation versus higher resource availability. Thus, the dual isotope model helps to interpret plant responses to a multitude of environmental factors.