Geometric relationships of neural and bony landmarks of the cranial base.

The skull base serves as structural support for the brain and as a conduit for neurovasculature. Traditional morphometric methods have intrinsic limitations which make wholistic assessment of this anatomy challenging. Here we applied geometric morphometric techniques to address the problems associated with traditional morphometric strategies for evaluating skeletal and soft tissue components of the skull base.

Anomalous Left Circumflex Artery Arising From the Right Coronary Artery: A Cadaveric Case Report and Review of the Literature.

Coronary artery anomalies are relatively rare in the general population; however, they remain clinically significant due to their varying effects on cardiovascular function and diagnostic and treatment outcomes. Here is described an anomalous left circumflex artery (ALCx) discovered during routine dissection of a 76-year-old female anatomical donor. The ALCx was seen arising from shared ostia with the right coronary artery and conus artery from the right aortic sinus of Valsalva, giving off the left atrial branch along its retroaortic course before reaching the left aspect of the coronary sulcus.

Resistance to antibacterial antifolates in multidrug-resistant Staphylococcus aureus: prevalence estimates and genetic basis.

Objectives: Antibacterial antifolate drugs might have a wider role in the management of staphylococcal infection. One factor that could potentially limit their use in this context is pre-existing resistance. Here we explored the prevalence and genetic basis for resistance to these drugs in a large collection (n = 1470) of multidrug-resistant (MDR) Staphylococcus aureus.

A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins.

The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes.

Successive remodeling of IgG glycans using a solid-phase enzymatic platform.

The success of glycoprotein-based drugs in various disease treatments has become widespread. Frequently, therapeutic glycoproteins exhibit a heterogeneous array of glycans that are intended to mimic human glycopatterns. While immunogenic responses to biologic drugs are uncommon, enabling exquisite control of glycosylation with minimized microheterogeneity would improve their safety, efficacy and bioavailability.

A kinase-cGAS cascade to synthesize a therapeutic STING activator.

The introduction of molecular complexity in an atom- and step-efficient manner remains an outstanding goal in modern synthetic chemistry. Artificial biosynthetic pathways are uniquely able to address this challenge by using enzymes to carry out multiple synthetic steps simultaneously or in a one-pot sequence. Conducting biosynthesis ex vivo further broadens its applicability by avoiding cross-talk with cellular metabolism and enabling the redesign of key biosynthetic pathways through the use of non-natural cofactors and synthetic reagents.

Design and Study of PEG Linkers That Enable Robust Characterization of PEGylated Proteins.

Several PEGylated therapeutic proteins are approved drugs, and more are under development. However, the synthesis and characterization of these bioconjugates, especially heterogeneous mixtures of PEGylated proteins, are challenging. The present study focuses on the development of PEG linkers that can be installed through biocatalytic route and render much simpler and insightful analytical characterization of PEG-protein conjugates.

Chemistry in the mail: Stamps from around the globe and public science communication in the twentieth century.

Postage stamps are designed to convey messages that reverberate symbolically with broad swaths of the public, and their content has been employed as a window into how members of the public understand the ideas represented therein. In this rhetorical analysis, we analyze Philadelphia's Science History Institute's Witco Stamp Collection, which features 430 stamps from countries around the globe dating from 1910 to 1983, to identify how chemistry is portrayed in this ubiquitous medium. We find the vernacular of science reflected and supported by these images functions to (a) define chemistry in terms of its invisibility and abstraction; (b) uphold chemical operations as instrumental and daedal, or exceptional, in nature; and (c) delineate practitioners of chemistry as-on the whole-privileged and preternatural.

In silico method development for the reversed-phase liquid chromatography separation of proteins using chaotropic mobile phase modifiers.

Recent advances in biomedical and pharmaceutical processes has enabled a notable increase of protein- and peptide-based drug therapies and vaccines that often contain a higher-order structure critical to their efficacy. Hyphenation of chromatographic and spectrometric techniques is at the center of all facets of biopharmaceutical analysis, purification and chemical characterization. Although computer-assisted chromatographic modeling of small molecules has reached a mature stage across the pharmaceutical industry, software-based method optimization approaches for large molecules has yet to see the same revitalization.

Aggressive versus conservative fluid resuscitation in septic hemodialysis patients.

Purpose: Sepsis and bacterial infections are common in patients with end-stage renal disease (ESRD). We aimed to compare patients with ESRD on hemodialysis presenting to hospital with severe sepsis or septic shock who received <20 ml/kg of intravenous fluid to those who received ≥20 ml/kg during initial resuscitation.

Materials And Methods: We conducted a retrospective chart review of adult patients with ICD codes for discharge diagnosis of sepsis, severe sepsis, septic shock, ESRD, and hemodialysis admitted to our institution between 2015 and 2018.

Introducing Multifactorial Peak Crossover in Analytical and Preparative Chromatography via Computer-Assisted Modeling.

Modern pharmaceutical processes can often lead to multicomponent mixtures of closely related species that are difficult to resolve under chromatographic conditions, and even worse in preparative scale settings. Despite recent improvements in column technology and instrumentation, there remains an urgent need for creating innovative approaches that address challenging coelutions of critical pair and poor chromatographic productivity of purification methods. Herein, we overcome these challenges by introducing a simple and practical technique named multifactorial peak crossover (MPC) via computer-assisted chromatographic modeling.

Introducing online multicolumn two-dimensional liquid chromatography screening for facile selection of stationary and mobile phase conditions in both dimensions.

Baseline separation and analysis of multicomponent mixtures of closely related pharmaceuticals using single column selectivity can often be challenging, requiring the combination of orthogonal stationary and mobile phase methods to monitor all the species and optimize reaction outcomes. In recent years, two-dimensional liquid chromatography (2D-LC) has become a valuable tool for improving peak capacity and selectivity. Though powerful, standard 2D-LC instrumentation and software can often lead to tedious method development and has a requirement for very specific expertise that is poorly suited for a fast-paced industrial environment.

Comprehensive online multicolumn two-dimensional liquid chromatography-diode array detection-mass spectrometry workflow as a framework for chromatographic screening and analysis of new drug substances.

The analysis of complex mixtures of closely related species is quickly becoming a bottleneck in the development of new drug substances, reflecting the ever-increasing complexity of both fundamental biology and the therapeutics used to treat disease. Two-dimensional liquid chromatography (2D-LC) is emerging as a powerful tool to achieve substantial improvements in peak capacity and selectivity. However, 2D-LC suffers from several limitations, including the lack of automated multicolumn setups capable of combining multiple columns in both dimensions.

Mass Activated Droplet Sorting (MADS) Enables High-Throughput Screening of Enzymatic Reactions at Nanoliter Scale.

Microfluidic droplet sorting enables the high-throughput screening and selection of water-in-oil microreactors at speeds and volumes unparalleled by traditional well-plate approaches. Most such systems sort using fluorescent reporters on modified substrates or reactions that are rarely industrially relevant. We describe a microfluidic system for high-throughput sorting of nanoliter droplets based on direct detection using electrospray ionization mass spectrometry (ESI-MS).

Design of an in vitro biocatalytic cascade for the manufacture of islatravir.

Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates.

Fluid resuscitation in patients with end-stage renal disease on hemodialysis presenting with severe sepsis or septic shock: A case control study.

Due to the potential risk of volume overload, physicians are hesitant to aggressively fluid-resuscitate septic patients with end-stage renal disease (ESRD) on hemodialysis (HD). Primary objective: To calculate the percentage of ESRD patients on HD (Case) who received ≥30 mL/Kg fluid resuscitation within the first 6 h compared to non-ESRD patients (Control) that presented with severe sepsis (SeS) or septic shock (SS). Secondary objectives: Effect of fluid resuscitation on intubation rate, need for urgent dialysis, hospital length of stay (LOS), intensive care unit (ICU) admission and LOS, need for vasopressors, and hospital mortality.

Medicalization's Communicative Infrastructure: Seventy Years of "Brain Chemistry" in the .

Medicalization theory aims to delineate how and why non-medical issues become demarcated within the realm of medical jurisdiction. The theory postulates that medicalization is marked by diagnostic naming, medical expertise, technological standardization and the de-contextualization of experiential knowledge, and that it is driven by popular media and lay discourse as much as by the communication of health professionals and medical institutions. Although medicalization has been recognized as an inherently rhetorical act, medicalization theory does not attend to the specific communicative means undergirding its orchestration.

Chaotropic Effects in Sub/Supercritical Fluid Chromatography via Ammonium Hydroxide in Water-Rich Modifiers: Enabling Separation of Peptides and Highly Polar Pharmaceuticals at the Preparative Scale.

Chromatographic separation, analysis and characterization of complex highly polar analyte mixtures can often be very challenging using conventional separation approaches. Analysis and purification of hydrophilic compounds have been dominated by liquid chromatography (LC) and ion-exchange chromatography (IC), with sub/supercritical fluid chromatography (SFC) moving toward these new applications beyond traditional chiral separations. However, the low polarity of supercritical carbon dioxide (CO) has limited the use of SFC for separation and purification in the bioanalytical space, especially at the preparative scale.

Doing more with less: Evaluation of the use of high linear velocities in preparative supercritical fluid chromatography.

The evaluation of higher than typical linear velocities is discussed for supercritical fluid chromatographic purifications on the preparative scale. SFC separation efficiency suffers far less at high linear velocities than HPLC by the rapid mass transfer of analytes carried by compressed CO through the stationary phase. The technique is discussed using chiral test compounds and columns.

Visualizing and studying frictional heating effects in reversed-phase liquid chromatography using infrared thermal imaging.

Column temperature control is a fundamental component of liquid chromatography experiments. However, it is typically monitored indirectly by tracking the temperature of an adjacent heating element that exchanges heat with the column in a controlled environment. The practice of not directly measuring the column temperature means that uncontrolled contributions of heat, such as frictional heating inside the column, can be overlooked.

Autism Narratives in Media Coverage of the MMR Vaccine-Autism Controversy under a Crip Futurism Framework.

While previous studies in health communication have examined online news media regarding autism, there is a lack of research that critically examines how such media representations may stigmatize autism and seeks to eliminate the condition, particularly in the context of the resurging measles, mumps, and rubella (MMR) vaccine-autism controversy. To address this gap in the literature, this study analyzes 153 articles that engage the MMR vaccine-autism controversy from the top 10 online news sources in the U.S.

Comparison of commercial organic polymer-based and silica-based monolithic columns using mixtures of analytes differing in size and chemistry.

Commercially available silica-based monolithic columns Chromolith RP-8e, Chromolith RP-18, and Chromolith HR RP-18, and polymer-based monolithic columns ProSwift RP-1S, ProSwift RP-2H, and ProSwift RP-3U varying in pore size and bonded phase have been tested for the fast separation of selected sets of analytes. These mixtures of analytes included small molecules (uracil, caffeine, 1-phenylethanol, butyl paraben, and anthracene), acylated insulins, and intact proteins (ribonuclease A, cytochrome C, transferrin, apomyoglobin, and thyroglobulin), and covered wide range of chemistries and sizes. Small molecules were well separated with a height equivalent to theoretical plate of 11-26 μm using silica-based monolithic columns, while organic polymer-based monoliths excelled in the fast sub 1 min baseline separations of large molecules.

Effects of pressure and frictional heating on protein separation using monolithic columns in reversed-phase chromatography.

Pressure is not typically controlled or adjusted independently of flow rate during method development in reversed-phase LC (RPLC). However, it has been shown that pressure has an effect on analyte molecular molar volume, and the magnitude of this effect is greater for proteins and ionizable compounds than neutral small molecules. This phenomenon has received attention recently in the context of porous sub-2-micron particle packed columns.