1-Deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the thiamin diphosphate (ThDP)-dependent formation of DXP from pyruvate and D-glyceraldehyde 3-phosphate. DXP is at a metabolic branch point in bacteria, feeding into the methylerythritol phosphate pathway to indispensable isoprenoids and acting as a precursor for biosynthesis of essential cofactors in central metabolism, pyridoxal phosphate and ThDP, the latter of which is also required for DXP synthase catalysis. DXP synthase follows a unique random sequential mechanism and possesses an unusually large active site. These features have guided the design of sterically demanding alkylacetylphosphonates (alkylAPs) toward the development of selective DXP synthase inhibitors. alkylAPs studied here display selective, low μM inhibitory activity against DXP synthase. They are weak inhibitors of bacterial growth in standard nutrient rich conditions. However, bacteria are significantly sensitized to most alkylAPs in defined minimal growth medium, with minimal inhibitory concentrations (MICs) ranging from low μM to low mM and influenced by alkyl-chain length. The longest analog (C8) displays the weakest antimicrobial activity and is a substrate for efflux via AcrAB-TolC. The dependence of inhibitor potency on growth environment emphasizes the need for antimicrobial screening conditions that are relevant to the in vivo microbial microenvironment during infection. DXP synthase expression and thiamin supplementation studies offer support for DXP synthase as an intracellular target for some alkylAPs and reveal both the challenges and intriguing aspects of these approaches to study target engagement.

BackgroundWe assessed a new robotic visualization platform with novel user-control features and compared its performance to the previous model of operative microscope.MethodsIn a neurosurgery research laboratory, we performed anatomical dissections and assessed robotic, exoscopic, endoscopic, fluorescence functionality. Usability and functionality were tested in the operating room over 1 year.ResultsThe robotic microscope showed higher sensitivity for fluorescein sodium, higher detail in non-fluorescent background, and recorded/presented pictures with color quality similar to observation through the oculars. PpIX visualization was comparable to the previous microscope. Near-infrared indocyanine green imaging 3-step replay allowed for more convenient accurate assessment of blood flow. Point lock and pivot point functions were used in dissections to create 3D virtual reality microsurgical anatomy demonstrations. Pivot point control was particularly useful in deep surgical corridors with dynamic retraction. 3D exoscopic function was successfully used in brain tumor and spine cases. Endoscopic assistance was used for around-the-corner views in minimally invasive approaches. We present illustrative cases highlighting utility and new ways to control the operative microscope.ConclusionImprovements of the robotic visualization platform include intraoperative fluorescence visualization using FNa, integrated micro-inspection tool, improved ocular imaging clarity, and exoscopic mode. New robotic movements positively assist the surgeon and provide improved ergonomics and a greater level of intraoperative comfort, with the potential to increase the viewing quality. New operational modes also allow significant impact for anatomy instruction. With the increasing number and complexity of functions, surgeons should receive additional training in order to avail themselves of the advantages of the numerous novel features.

Although severe cases and mortality of coronavirus disease 2019 are proportionally infrequent, these cases are strongly linked to patients with conditions of metabolic syndrome (obesity, hypertension, diabetes, and dyslipidemia). However, the pathophysiology of COVID-19 in relation to metabolic syndrome is not well understood. Thus, the goal of this secondary literature review was to examine the relationship between severe acute respiratory syndrome (SARS-CoV-2) infection and the individual conditions of metabolic syndrome.The objective of this secondary literature review was achieved by examining primary studies, case studies, and other secondary studies, to obtain a comprehensive perspective of theories and observations of COVID-19 etiology with metabolic syndrome. The most extensive research was available on the topics of diabetes, hypertension, and obesity, which yielded multiple (and sometimes conflicting) hypothetical pathophysiology. The sources on dyslipidemia and COVID-19 were scarcer and failed to provide an equally comprehensive image, highlighting the need for further research.It was concluded that hypertension had the strongest correlation with COVID-19 incidence (followed by obesity), yet the causative pathophysiology was ambiguous; most likely related to cardiovascular, angiotensin-converting enzyme 2 (ACE-2)-related complications from renin-angiotensin-aldosterone system (RAAS) imbalance. Obesity was also positively correlated to the severity of COVID-19 cases and was believed to contribute to mechanical difficulties with respiration, in addition to hypothetical connections with the expression of ACE-2 on abundant adipose tissue. Diabetes was believed to contribute to COVID-19 severity by producing a chronic inflammatory state and interfering with neutrophil and T-cell function. Furthermore, there were indications that COVID-19 may induce acute-onset diabetes and diabetic ketoacidosis. Lastly, dyslipidemia was concluded to potentially facilitate SARS-CoV-2 infection by enhancing lipid rafts and immunosuppressive functions. There were also indications that cholesterol levels may have prognostic indications and that statins may have therapeutic benefits.

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