Autoimmune diseases including systemic sclerosis (SSc) increase risk of developing TB. Pericostal tuberculosis (TB) is a rare presentation of skeletal TB. This case report describes pericostal TB in a SSc patient, and emphasizes significance of suspecting pulmonary and extra-pulmonary TB when patients with autoimmune disease follow atypical clinical courses.

The compound 3′-phosphoadenosine-5′-phosphosulfate (PAPS) serves as a sulfate group donor in the production of valuable sulfated compounds, such as glycosaminoglycan and oxamniquine. However, elevated costs and low conversion efficiency limit the industrial applicability of PAPS. Here, we designed and constructed an efficient and controllable catalytic system for the conversion of ATP (disodium salt) into PAPS without inhibition from by-products. In vitro and in vivo testing in Escherichia coli identified adenosine-5′-phosphosulfate kinase from Penicillium chrysogenum (PcAPSK) as the rate-limiting enzyme. Based on analysis of the catalytic steps and molecular dynamics simulations, a mechanism-guided “ADP expulsion” strategy was developed to generate an improved PcAPSK variant (L7), with a specific activity of 48.94 U·mg-1 and 73.27-fold higher catalytic efficiency (kcat/Km) that of the wild-type enzyme. The improvement was attained chiefly by reducing the ADP-binding affinity of PcAPSK, as well as by changing the enzyme’s flexibility and lid structure to a more open conformation. By introducing PcAPSK L7 in an in vivo catalytic system, 73.59 mM (37.32 g·L-1) PAPS was produced from 150 mM ATP in 18.5 h using a 3-L bioreactor. The achieved titer is the highest reported to date and corresponds to a 98.13% conversion rate. The proposed strategy will facilitate industrial production of PAPS as well as the engineering of similar enzymes.

Uncertain fractional-order differential equations driven by Liu process are of significance to depict the heredity and memory features of uncertain dynamical systems. This paper primarily investigates the reliability analysis of the uncertain fractional-order dynamic system with a state constraint. On the basis of the first-hitting time (FHT), a novel uncertain fractional-order dynamic system considering a state constraint is proposed. Secondly, in view of the relation between the initial state and the required standard, such uncertain fractional-order dynamic systems are subdivided into four types. The concept of reliability of proposed uncertain system with a state constraint is presented innovatively. Corresponding reliability indexes are ulteriorly formulated via FHT theorems. Lastly, the uncertain fractional-order dynamic system with a state constraint is applied to different physical and financial dynamical models. The analytic expression of the reliability index is derived to demonstrate the reasonableness of our model. Meanwhile, expected time response and American barrier option prices are calculated by using the predictor-corrector scheme. A sensitivity analysis is also illustrated with respect to various conditions.

A document by Nathalia, written on Authorea.

The increasing salinization of coastal areas of Bangladesh reduces options for rice intensification but offers a suitable environment for shrimp and salt farming. Under these contested land use settings, adaptation decisions to address salinity require an understanding of the salinity perspectives of all farmer types. Primary data was collected from randomly selected rice, shrimp and salt farmers in two coastal sub-districts through semi-structured interviews at household level. Also, key informant interviews (KIIs) were conducted with personnel from research and extension organisations from different levels (e.g. national and local). Salinity perceptions among the various types of farmer differed. While the majority of rice farmers (87%) perceived increased salinity, just over half of the salt and shrimp farmers perceived that salinity has decreased over the past 20 years. Most rice farmers (62%) perceived anthropogenic factors as the main cause of increased salinity, while the majority of shrimp and salt farmers focused more on natural factors. Rice farmers perceived under saline conditions a yield loss (42%), followed by less income (30%). In contrast, shrimp farmers (70%) and salt farmers (55%) perceived production gains when high salinity prevailed. Rice farmers’ adaptation preferences to cope with salinity is development of salinity-tolerant rice varieties that have greater tolerance at the reproductive stages, while shrimp and salt farmers’ preferences are engineering-based solutions. Thus, research and extension services on integrated coastal resources management need to consider all livelihood perspectives, as this approach could accelerate the pace of achieving the SDGs (i.e.. SDG-1, SDG-2 and SGD-3).

The March/April issue of CiSE's inaugural year (1999) carried an essay by eminent computer science professor John R. Rice (who at the time was area editor for Software, together with Matlab inventor Cleve Moler) titled A Perspective on Computational Science in the 21st Century \cite{Rice_1999}. In it, he looked at the development directions for the future of computational science and engineering, and threaded across these was what he called "problem-solving environments." This routine-sounding term hides an ambitious vision, for the time. Rice imagined a software system for tackling problems within a science domain without all the agonizing toil of programming by hand every solution method. He and Ronald Boisvert had a previous article (1996) explaining the idea in more detail \cite{Rice_1996}. A problem-solving environment would include a collection of mathematical and domain-specific software libraries, offer (semi-)automatic selection of solution method for a given problem, help check the problem formulation, display or assess the correctness of solutions, allow extensibility to add new methods, and even manage the overall computational process. They envisaged an environment that could be "all things to all people," meaning: it is effective when solving simple or complex problems, it supports rapid prototyping and detailed analysis, and it can be used both in introductory teaching and in productive research at the edges of knowledge. An ideal problem-solving environment would even make decisions for the user by means of an integrated knowledge base. What fabulous ambition!Prof. Rice led a research group at Purdue University that worked to develop early problem-solving environments. The Ellpack system for solving elliptic boundary value problems, developed in the early 1980s, included dozens of software modules implementing solution methods and a descriptive language to formulate problems (today, we might call it a domain-specific language, DSL). For example, the line: equation. uxx + uyy + 3 * ux - 4 * u = exp(x+y) * sin(pi * x) would be used in an Ellpack program for defining the differential equation to be solved. Similarly expressive statements would define the boundary conditions, and the grid parameters to discretize the domain (a full example at https://www.cs.purdue.edu/ellpack/example.html). Later versions of the system offered parallel solvers and a graphical user interface (screenshots of the Ellpack system from Prof. John R. Rice's website at Purdue can be found in the Internet Archive https://web.archive.org/web/19990506040312/https://www.cs.purdue.edu/research/cse/index.html).While Ellpack was licensed by Purdue University for a modest yearly fee, this project did not branch off commercially or otherwise. Perhaps a few hundred copies were distributed, mostly for use in university settings, and the project wound down by the early 2000s. By contrast, three commercial software packages for high-productivity scientific and engineering computation—Maple, Mathematica, and Matlab—had by then become very popular \cite{Chonacky_2005}. These systems continue to be widely used in education, industry, and government settings. Their purchase price and proprietary implementations, however, led many champions of open-source software to conceive alternatives, oftentimes closely imitating their functionality.In March/April 2011, twelve years after Prof. Rice's Perspective essay, CiSE ran a special issue on Python for Scientific Computing, showcasing a maturing stack of tools and a highly productive environment for researchers. The issue included one of the most-widely cited articles in the history of the magazine, discussing the high-level multidimensional array structure at the core of NumPy \cite{van_der_Walt_2011}. By this time, the scientific community had expanded Python for its purposes, and the four keystone libraries had been put in place in the first half of the decade: SciPy was consolidated as a standard collection of modules for common mathematical and statistical functions.The first version of IPython, an enhanced interactive shell for Python, was created by Fernando Pérez.Matplotlib, the rich 2D visualization and now standard Python plotting library, was released by John Hunter.Travis Oliphant created NumPy from a rewrite of the early Python array library Numeric, adding functionality from the competing array package called numarray.CiSE had previously featured the developing Python support for scientific workflows in an issue organized by Paul F. Dubois, who was the project lead for Numeric from 1997 to 2002. Paul was an editor for Computer in Physics (which got merged into CiSE) since 1993, and joined CiSE with its founding. He wrote and edited for the Scientific Programming department until 2006, and continued with the column "Café Dubois" until 2008. The issue he led included the Hunter piece on Matplotlib \cite{Hunter_2007}, the Pérez and Granger article about IPython \cite{Perez_2007}, and Travis Oliphant's general overview of the Python language and its extensions with NumPy and SciPy \cite{Oliphant_2007}. Other articles in the issue highlight applications in various science contexts: space observation, systems biology, robotics, nanophotonics, and more. An author team from the Simula Research Laboratory in Norway discussed new Python tooling for solving partial differential equations with finite element methods in what was the early development of the Fenics project (http://www.fenics.org/) \cite{Mardal_2007}. This work heralded the compelling combination of symbolic mathematics and code generation, which Ellpack anticipated.

Abstract: Background: This meta-analysis assessed the relationship between Obstructive Sleep Apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of Heart Failure with Preserved Ejection Fraction (HFpEF). Methods: We searched the databases including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26th, 2020. The search was not restricted to time, publication status or language. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography (PSG) or home sleep apnea testing (HSAT), and patients without OSA in relation to established markers of diastolic dysfunction. Results: Primary search identified 2512 studies. A total of 18 studies including 2509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater LAVI (3.94 CI [0.8, 7.07]; p=0.000) and left ventricular mass index (11.10 CI [2.56,19.65]; p=0.000) as compared to control group. The presence of OSA was also associated with more prolonged DT (10.44 ms CI [0.71,20.16]; p=0.04), IVRT (7.85 ms CI[4.48, 11.22]; p=0.000), and lower E/A ratio (-0.62 CI [-1,-0.24]; p=0.001) suggestive of early DD. The E/e’ ratio (0.94 CI[0.44, 1.45]; p=0.000) was increased. Conclusion: An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of CPAP therapy in reversing or ameliorating diastolic dysfunction is recommended.

Seneca Valley Virus (SVV) infection has recently spread to pig farms in Canada, America, and China. Humans, mice, and houseflies have been identified as hosts and reservoirs. Although such cross-species transmission events are often limited, sustained outbreaks in a new mammalian host can occur. To determine if mink are a new mammalian host of SSV, we studied the molecular characteristics of isolated SVV genomes and analyzed challenge, pathology, and immune response data. The study was the first systemic analysis of a newly isolated strain of SVV from pigs. The strain caused an intestinal infection with associated pathologic changes in mink. SVV stimulated the production of a specific neutralizing antibody. The findings highlight the importance of identifying SVV infection in mink and the host to detect mutated SSV that could threaten livestock and pose public health and economic risks.

Objectives: To examine the effects of estrogen on all-cause mortality, cancers, cardiovascular (CV) conditions, and dementia. Design: Retrospective observational study Setting: United States 2007-2018 Population: 1.5 million women aged over 65 in Medicare. Method: Cox regression with time-varying estrogen type, route, and strength as well as patient’s characteristics. Main Outcome(s): all-cause mortality; 5 cancers- breast, lung, endometrial, colorectal, ovarian cancers; 6 CV conditions- ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction; and dementia. Results: Compared to counterparts, estrogen monotherapy (ET) exhibited a significant, 21% (HR=0.79; 95% CI 0.77-0.81), reduction in mortality risk. The reduction was greater with estradiol (HR=0.76; 95% CI 0.73-0.78) than conjugated estrogen (HR=0.83; 95% CI 0.80-0.86), and with topical (HR=0.69; 95% CI 0.66-0.71) than oral preparations (HR=0.86; 95% CI 0.83-0.89). ET also exhibited significant risk reductions for all study cancers, breast (HR=0.83; 95% CI 0.80-0.85), lung (HR=0.89; 95% CI 0.85-0.93), endometrial (HR=0.68; 95% CI 0.63-0.73), colorectal (HR=0.87; 95% CI 0.82-0.92) and ovarian (HR=0.86; 95% CI 0.80-0.92). Different dose levels exhibited similar risk reduction in mortality and cancers. ET slightly increased the overall CV risk, mostly risks of ischemic heart diseases and stroke. However, such risks occurred with CEE, oral, and high dose ET. Both combination therapy (HR=1.19; 95% CI 1.08-1.31) and progestogen monotherapy (HR=1.16; 95% CI 1.08-1.26) exhibited a significantly increased risk of breast cancer. No HT exhibited an increased risk of dementia. Conclusions: Among senior female Medicare beneficiaries, the effect of hormone therapy varies by type, route, and strength of estrogen.

Aims: Amidst the Campos the Altitude (Highland Grasslands) in the Brazilian Atlantic Forest, woody communities grow either clustered in tree islands or interspersed within the herbaceous matrix. The functional ecology, diversity and biotic processes shaping these communities are largely unstudied. We characterised the functional assembly and diversity of these tropical montane woody communities and investigated how those communities fit within the Grime’s CSR (C – competitor, S – stress-tolerant, R – ruderal) scheme, what trade-offs they exhibit and how traits and functional diversity vary in response to bamboo invasion. Methods: We sampled five leaf traits and wood density along transects covering the woody communities both inside tree islands and outside (i.e. woody plants in the grasslands community) to characterise the functional ecology of the community. We used Kruskal-Wallis test, t-test and variation partitioning to determine effects of inside vs outside the tree island and bamboo invasion on traits, woody species diversity and functional diversity. Results: We found a general SC/S strategy with drought-related functional trade-offs. Woody plants in tree islands had more acquisitive traits, whereas woody plants within the grasslands had more conservative traits. Trait variation was mostly taxonomically driven, and species composition varied between inside and outside tree islands. Leaf thickness, wood density and foliar water uptake were unrelated to CSR-strategies, suggesting independent trait dimensions and multiple drought-coping strategies within the predominant S-strategy. Bamboo-invaded islands showed lower Simpson diversity, lower functional dispersion, lower foliar water uptake and greater leaf thickness than non-invaded tree islands. Conclusions: The observed functional assembly in response to bamboo and facilitation have implications for future forest expansion and response of the communities to climate change. Further studies on eco-physiological and establishment traits and the mechanisms behind biotic interactions are needed to better understand the response of these communities to future environmental changes.

Abstract Aim: The invasion process is a complex, context-dependent phenomenon; nevertheless, it can be described using the PAB framework. This framework encompasses the joint effect of propagule pressure (P), abiotic characteristics of the environment (A), and biotic characteristics of both the invader and recipient vegetation (B). We analyzed the effectiveness of proxies of PAB factors to explain the spatial pattern of Solidago canadensis and S. gigantea invasion using invasive species distribution models. Location: Carpathian Mountains and their foreground, Central Europe. Methods: The data on species presence or absence were from an atlas of neophyte distribution based on a 2 × 2 km grid, covering approximately 31,200 km2 (7752 grid cells). Proxies of PAB factors, along with data on historical distribution of invaders were used as explanatory variables in Boosted Regression Trees models to explain the distribution of invasive Solidago. The areas with potentially lower sampling effort were excluded from analysis based on a target species approach. Results: Proxies of the PAB factors helped to explain the distribution of both S. canadensis and S. gigantea. Distributions of both species were limited climatically because a mountain climate is not conducive to their growth; however, the S. canadensis distribution pattern was correlated with proxies of human pressure, whereas S. gigantea distribution was connected with environmental characteristics. The varied responses of species with regard to distance from their historical distribution sites indicated differences in their invasion drivers. Main conclusions: Proxies of PAB are helpful in the choice of explanatory variables as well as the ecological interpretation of species distribution models. The results underline that human activity can cause variation in the invasion of ecologically similar species.

1. Plant-soil feedback (PSF) has gained attention as a mechanism promoting plant growth and coexistence. However, because most PSF research has measured monoculture growth in greenhouse conditions, field-based PSF experiments remain an important frontier for PSF research. 2. Using a four-year, factorial field experiment in Jena, Germany, we measured the growth of nine grassland species on soils conditioned by each of the target species (i.e., PSF). Plant community models were parameterized with or without these PSF effects, and model predictions were compared to plant biomass production in new and existing diversity-productivity experiments. 3. Plants created soils that changed subsequent plant biomass by 36%. However, because they were both positive and negative, the net PSF effect was 14% less growth on ‘home’ than ‘away’ soils. At the species level, seven of nine species realized non-neutral PSFs, but the two dominant species grew only 2% less on home than away soils. At the species*soil type level, 31 of 72 PSFs differed from zero. 4. In current and pre-existing diversity-productivity experiments, nine-species plant communities produced 37 to 29% more biomass than monocultures due primarily to selection effects. Null and PSF models predicted 29 to 28% more biomass for polycultures than monocultures, again due primarily to selection effects. 5. Synthesis: In field conditions, PSFs were large enough to be expected to cause roughly 14% overyielding due to complementarity, however, in plant communities overyielding was caused by selections effects, not complementarity effects. Further, large positive and large negative PSFs were associated with subdominant species, suggesting there may be selective pressure for plants to create neutral PSF. Broadly, results highlighted the importance of testing PSF effects in communities because there are several ways in which PSFs may be more or less important to plant growth in communities than suggested from simple PSF values.

Objectives: A retrospective review of adolescent and adult patients with Atrial Septal Defect (Secundum ASD) who underwent secundum ASD closure by transcatheter closure (TCC) or surgery at Jordan University Hospital (JUH). We seek to illustrate the importance of a multidisciplinary Heart Team in low-volume centres, and report the experience and outcomes of this approach. Methodology: A retrospective observational study of 42 patients who underwent secundum ASD closure by TCC or surgery at JUH. We utilised the hospital’s electronic record system to attain patients’ information, and SPSS and Microsoft Excel were used to analyse the data. Results: 42 patients with secundum ASD were treated during the period between January 2015 and December 2019. The mean age of participants was 34.1 (± 14.3). A total of 34 patients underwent TCC, seven surgical closure, and one a hybrid approach. There were no incidents of mortality, but two minor morbidities were reported. After an average follow-up period of 13.2-/+13.6 months, with a range of 1-47 months , most patients experienced an improvement in their symptoms. There was also a significant reduction of the right ventricular dimension: Conclusion: A Heart Team approach is necessary as the use of minimally invasive cardiac surgery MICS and Transcatheter closure TCC continues to advance. A Heart Team provides patients with a variety of safe and cosmetic solutions that facilitate rapid management and recovery by encouraging the merits and avoiding the complications of each modality. Ultimately, the Heart Team allows low-volume centres to achieve excellent outcomes.

A 19-year-old pregnant patient was diagnosed with primary toxoplasmosis infection. The patient was successfully treated with spiramycin and finally delivered normally a healthy boy. Serological tests for detection of anti-toxoplasma antibodies along with ultrasonography findings are the gold standard for the diagnosis. Spiramycin was used for embryo protection.

We present a case of a 25 year-old female who developed acute hypoxic respiratory failure secondary to postpartum heart failure with preserved ejection fraction. Despite essentially normal tissue Doppler velocities and E/e’ ratio by existing guidelines for the adult population, available literature suggests that our patient’s markers of diastolic function were significantly abnormal relative to what is expected in the third trimester of pregnancy. Advanced echo-Doppler analysis and her clinical presentation support the presence of underlying diastolic dysfunction. This case illustrates the challenges associated with the diagnosis of diastolic dysfunction during pregnancy and the need for pregnancy specific guidelines.

The purpose of this paper is to provide the calculation methods on worm addendum thickness and curvature interference limit line, and find the feasible value range of the technological crossing angle to avoiding addendum sharpening and curvature interference for enveloping cylindrical worm drive with arc-toothed worm. In accordance with the features of the proposed worm, the mathematical models of cutting and working are established. Based on this, the tooth profile geometry of the worm in its axial section and the worm addendum thickness are obtained by geometric analysis and calculation, and then, the feasible value range of the technological crossing angle is given. In virtue of vector rotation and elimination method, the nonlinear equation with one variable for solving the interference limit line is determined. In the process of solving nonlinear equation, the method of geometric construction is used to judge the existence of solutions and provide an initial value for the subsequent iterative calculation. The numerical example results show that with the increases of the technological crossing angle, the interference limit line is close to the boundary line of the conjugate region of the worm pair, and the hazard of curvature interference evident increases. Generally, a smaller value of the technological crossing angle within its available value range can completely avoid the occurrence of the curvature interference.

Aim: It is a well-known fact that inflammation plays a crucial role in many diseases including COVID-19. Using flow-mediated dilatation (FMD), we aimed to compare the effects of inflammation on endothelial dysfunction in patients with COVID-19 and the control group. Materials and Methods: The present study was conducted on a total of 161 participants, of whom 80 were diagnosed with COVID-19 within the last 6 months (comprising 48 women and 32 men with a mean age of 32.10 ± 5.87 years) and 81 were healthy controls (comprising 45 women and 36 men with a mean age of 30.51 ± 7.33 years). We analyzed the findings of transthoracic echocardiography and FMD in all participants. Results: Except for FMD, there was no statistically significant difference in echocardiographic parameters. (9.52 ± 5.98 vs. 10.53 ± 6.31, p=0.010). In multivariate analysis with the forward stepwise model, FMD was significantly different in the control group compared to the COVID group (1.086 (1.026 - 1.149), p=0.04). Spearman’s correlation test indicated that FMD (r=0.27, p=0.006) had a significantly positive correlation with the presence of COVID. A receiver operating curve analysis revealed that an FMD value of <10.62% was capable of predicting the presence of COVID with a sensitivity and specificity of 64% and 59%, respectively (AUC=0.625, 95% CI, 0.538 - 0.711). Conclusion: The value of FMD decreased significantly in COVID-19 patients compared to the healthy subjects, which may be an early marker for COVID-19 induced endothelial dysfunction. KEYWORDS: COVID-19, endothelial dysfunction, flow-mediated dilatation (FMD

Background: Right Ventricular (RV) failure has a critical role in the onset and progression of clinical symptoms and the prognosis of patients with Mitral Stenosis (MS), but the exact role, effect, and pathophysiology of RV dysfunction in MS is still controversial. In this study, we aimed to evaluate echocardiographic signs of systolic RV dysfunction using Tissue Doppler Imaging (TDI) and Velocity Vector Imaging (VVI) in subjects with severe and very severe MS. Methods: 46 isolated MS cases (23 severe and 23 very severe) and 23 healthy controls were enrolled in this study. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and peak systolic velocity of the tricuspid annulus (S’) using TDI, and RV free wall strain (RVFWS) employing VVI. Furthermore, these values were compared with mitral valve area (MVA) and pulmonary arterial pressure (PAP). Results: TAPSE, FAC, S’, and RVFWS values were substantially declined in MS cases compared with healthy controls. Moreover, PAP values were considerably increased in MS subjects. Additionally, S’ and TAPSE values were significantly lower in very severe MS patients compared with severe patients. Conclusion: RV systolic function deteriorates in patients with severe and very severe MS. It appears that the degree of the severity of MS can proportionately affect the extent of RV dysfunction and some of its echocardiographic markers such as S’ and TAPSE. TDI and VVI can be used as practical early diagnostic methods for RV dysfunction in MS.

The THAP (Thanatos-associated protein) domain is a DNA-binding domain which binds DNA via a zinc coordinating C2CH motif. Although THAP domains share a conserved structural fold, they bind different DNA sequences in different THAP proteins, which in turn perform distinct cellular functions. In this study, we investigate (using multiple sequence alignment, in silico motif and secondary structure prediction) THAP domain conservation within the homologs of the human THAP (hTHAP) protein family. We report that there is significant variation in sequence and predicted secondary structure elements across hTHAP homologs. Interestingly, we report that the THAP domain can be either longer or shorter than the conventional 90 residues and the amino terminal C2CH motif within the THAP domain serves as a hotspot for insertion or deletion. Our results lay the foundation for future studies which will further our understanding of the evolution of THAP domain and regulation of its function.

Aims: Assessing the suitability and safety of doses of levetiracetam in pediatrics using physiologic-based pharmacokinetic (PBPK) modeling. Methods: A PBPK model of levetiracetam was developed and validated for healthy adults and scaled for children (0.5 to 12 years old). Prediction of levetiracetam exposure at steady- state, were carried out for different therapeutic regimens to achieve the target of Cmax values within the therapeutic range of 5 to 46 µg ml-1. Then, a multivariate linear regression analysis (MLR) was applied to correlate the simulated data with covariates: dose, therapeutic regimen, sex, age and body weight (BW), to describe the best model prediction for the initial dosing in pediatrics. Results: The results indicated the suitability of the PBPK model for adults and pediatrics. For children aged 0.5 to 6 y.o. the dose range capable of reaching the pharmacokinetic target is between 10 and 100 mg kg-1 day-1, for 7 to 9 y.o. doses between 20 and 90 mg kg-1 day-1, and for 10 to 12 y.o. doses between 20 to 80 mg kg-1 day-1. Further, the MLR related Cmax to dose, therapeutic regimen, and BW. Conclusions: For 3 daily administrations, it is suggested that maximum daily doses of 80 mg kg-1 could be used for ages between 0.5 and 6 y.o. and 100 mg kg-1 for ages above 7 years old, since they weigh below 50 kg. The PBPK model lumped to MLR could be very supportive for clinical decisions to safety and effectiveness of prescription of levetiracetam along the titration phase.

A document by Rob Salguero-Gómez, written on Authorea.

In insect societies, the queen monopolizes reproduction while workers perform tasks such as brood care or foraging. Queen loss leads to ovary development and lifespan extension in workers from many ants. However, the underlying molecular mechanisms of this phenotypic plasticity remain unclear. Recent studies highlight the importance of epigenetics in regulating plastic traits in social insects. We investigated the role of histone acetylation in the regulation of worker reproduction in the ant Temnothorax rugatulus. We removed queens from their colonies to induce worker fecundity, and either fed workers with chemical inhibitors of histone acetylation (C646), deacetylation (Trichostatin A), or the solvent (DMSO) as control. We monitored worker number for six weeks after which we assessed ovary development and sequenced fat body mRNA. Workers survived better in queenless colonies and developed their ovaries after queen removal in control colonies as expected, but not in colonies treated with chemical inhibitors. Both inhibitors affected gene expression, although the inhibition of histone acetylation using C646 influenced the expression of more genes with immunity, fecundity, and longevity functionalities. Interestingly, these C646-treated workers shared many upregulated genes with infertile workers from queenright colonies. We also identified one gene with antioxidant properties commonly downregulated in infertile workers from queenright colonies and both C646 and TSA-treated workers from queenless colonies. Our results indicate that histone acetylation is involved in the molecular regulation of worker reproduction and lifespan, and thus point to an important role of histone modifications in modulating phenotypic plasticity of life history traits in social insects.

Introduction Vascular access has traditionally been gained from the femoral vessels, however, a ‘radial-first’ approach has become increasingly popular and resulted in lower complication rates and reduced healthcare costs. A “superior” approach has been reported for electrophysiology (EP) studies but is associated with an increased risk. To provide comprehensive anatomical evidence that the vessels of the arms are suitable for use during EP procedures, as assessed by vascular ultrasound. Methods A portable ultrasound device was used to measure the diameter of the brachial artery, brachial, basilic & cephalic veins on the left and right upper limbs of 63 healthy volunteers. A subgroup of 15 volunteers had additional measurements taken with a tourniquet. Results The basilic vein had the largest diameter with a median of 4.6 mm and 4.5 mm (right and left diameter, respectively), followed by the cephalic (median of 3.1 and 3.0 mm) and the brachial vein (median of 2.8 mm). 100% of volunteers had at least one vein that was equal to a 3 mm diameter (which would allow for an 8F sheath), with 98% having 2 suitable veins and >80% having 3 suitable venous vessels. More than 90 % had a suitable diameter for both the right and left brachial artery. There was no correlation between BMI, height, weight, but men had significantly larger basilic veins and brachial arteries (p<0.05). Conclusion We demonstrate the anatomic evidence that the vessels in the arm(s) are capable of housing the size of sheath commonly used in the EP lab.

Rationale & Objective: Hyperphosphatemia is present in most patients with end-stage renal disease (ESRD) and has been associated with increased cardiovascular mortality. Phosphate binders (calcium-based and calcium free) are the mainstay pharmacologic treatment to lower phosphorus levels in patients with ESRD. Study Design: We evaluated biochemical markers of vascular calcification, inflammation, and endothelial dysfunction in patients with Chronic Kidney Disease (CKD) treated with sevelamer carbonate versus calcium acetate. Setting & Participants: We enrolled 50 CKD patients (stages 3 and 4) and treated them with sevelamer carbonate and calcium acetate for 12 weeks. Outcomes: At the end of the study the biomarkers of vascular calcification, inflammation, and endothelial dysfunction were analyzed. Results: A significant increase in HDL-cholesterol was observed with sevelamer carbonate but not with calcium acetate. Treatment with sevelamer carbonate reduced serum phosphate, calcium phosphate, and FGF-23 levels and there was no change with calcium acetate treatment. The inflammatory markers IL-8, IFN-γ, and TNFα decreased with response to both treatments. The levels of IL-6 significantly increased with calcium acetate treatment and no change was observed in the sevelamer carbonate treatment group. Conclusion: Sevelamer carbonate showed favorable effects on anti-inflammatory and vascular calcification biomarkers compared to calcium acetate treatment. Funding: Funding was received from Sanofi/Genzyme. Trial Registration: Registered at trial.com, registration number NCT01277497.