Henoch-Schönlein purpura in the setting of COVID-19 infection: Two pediatrics cases and review of the literature.

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, often following a viral infection. Various types of rashes attributed to COVID-19 infection have been described in the literature; however, HSP has rarely been reported. We report two children with HSP associated with acute COVID-19 infection with a review of the available literature. We highlight the clinical presentation, medical management, outcome and age-related difference of reported patients. A limitation of this article is the retrospective nature, limiting full patient history and associated conditions. The findings of this review show that HSP in the setting of COVID-19 is more common in children than adults, with a male predominance, involving various body systems creating a constellation of presentations. Given that HSP can have long-term morbidity from renal disease if untreated, this review may help guide the practitioner's approach to HSP and recognition in the setting of COVID-19 infection.

Discrepancy between DXA and CT-based assessment of spine bone mineral density.

PURPOSE: Adequate bone mineral density (BMD) is necessary for success in spine surgery. Dual-energy X-ray absorptiometry (DXA) is the gold standard in determining BMD but may give spuriously high values. Hounsfield units (HU) from computed tomography (CT) may provide a more accurate depiction of the focal BMD encountered during spine surgery. Our objective is to determine the discrepancy rate between DXA and CT BMD determinations and how often DXA overestimates BMD compared to CT. METHODS: We retrospectively reviewed 93 patients with both DXA and CT within 6 months. DXA lumbar spine and overall T scores were classified as osteoporotic (T Score ≤ - 2.5) or non-osteoporotic (T Score > -2.5). L1 vertebral body HU were classified as osteoporotic or non-osteoporotic using cutoff thresholds of either ≤ 135 HU or ≤ 110 HU. Corresponding DXA and HU classifications were compared to determine disagreement and overestimation rates. RESULTS: Using lumbar T scores, the CT vs DXA disagreement rate was 40-54% depending on the HU threshold. DXA overestimated BMD 97-100% of the time compared to CT. Using overall DXA T scores, the disagreement rate was 33-47% with DXA greater than CT 74-87% of the time. In the sub-cohort of 10 patients with very low HU (HU < 80), DXA overestimated BMD compared to CT in every instance. CONCLUSIONS: There is a large discrepancy between DXA and CT BMD determinations. DXA frequently overestimates regional BMD encountered during spine surgery compared with CT. While DXA remains the gold standard in determining BMD, CT may play an important role in defining the focal BMD pertinent to spine surgery.

Developmental Self-Assembly of a DNA Ring with Stimulus-Responsive Size and Growth Direction.

Developmental self-assembly of DNA nanostructures provides an ideal platform for studying the power and programmability of kinetically controlled structural growth in engineered molecular systems. Triggered initiation and designated sequencing of assembly and disassembly steps have been demonstrated in structures with branches and loops. Here we introduce a new strategy for selectively activating distinct subroutines in a developmental self-assembly program, allowing structures with distinct properties to be created in response to various molecular signals. We demonstrate this strategy in triggered self-assembly of a DNA ring, the size and growth direction of which are responsive to a key molecule. We articulate that reversible assembly steps with slow kinetics at appropriate locations in a reaction pathway could enable multiple populations of structures with stimulus-responsive properties to be simultaneously created in one developmental program. These results open up a broad design space for the self-assembly of molecules with adaptive behaviors toward advanced control in synthetic materials and molecular motors.

A Cooperative DNA Catalyst.

DNA catalysts are fundamental building blocks for diverse molecular information-processing circuits. Allosteric control of DNA catalysts has been developed to activate desired catalytic pathways at desired times. Here we introduce a new type of DNA catalyst that we call a cooperative catalyst: a pair of reversible reactions are employed to drive a catalytic cycle in which two signal species, which can be interpreted as an activator and an input, both exhibit catalytic behavior for output production. We demonstrate the role of a dissociation toehold in controlling the kinetics of the reaction pathway and the significance of a wobble base pair in promoting the robustness of the activator. We show near-complete output production with input and activator concentrations that are 0.1 times the gate concentration. The system involves just a double-stranded gate species and a single-stranded fuel species, as simple as the seesaw DNA catalyst, which has no allosteric control. The simplicity and modularity of the design make the cooperative DNA catalyst an exciting addition to strand-displacement motifs for general-purpose computation and dynamics.

Rapid shoreline erosion and dunefield Change, Salmon Hole, South Australia.

Since the 1940's, rapid shoreline and dunefield changes have been ongoing at Salmon Hole, an embayment situated near Beachport in the SE of South Australia. Storm induced erosion has nearly removed the entire dunefield and created a lagoon confined by a calcarenite reef. This study examines the progress, dynamics and causes of the erosion to determine why it has been so severe, using historical aerial imagery, wave reanalyses data, Digital Surface Models (DSM's) from drone surveys and through the volumetric analysis of topographic profiles. The results gained through analysing shoreline change at Salmon Hole are then discussed based on Phillips (2009) change assessment system. This study found that a combination of the formation of the 'lagoon' between the mainland/dune system and the offshore reef and the resultant breakthrough of the tombolo that have led to the acceleration of the erosion processes seen at Salmon Hole. The formation of the lagoon initiated a divergent evolution that continues in the form of a significant geologically controlled longshore current and terminal rip that enhances removal of sediment during and following erosion of the dunes. It appears that each time the lagoon widened post storm erosion it resulted in an increase in the efficiency of the current, resulting in a positively reinforcing feedback loop furthering the erosion level during each successive storm. The profiles taken from the drone survey DEM's reveal the processes involved in scarping and demonstrate how dune systems with zero sediment supply will respond to future climate and wave conditions. Coastal systems experiencing a deficit in sediment supply will not be able to translate landwards/upwards resulting in their removal. If the current rate of erosion at Salmon Hole is maintained into the future, the entire system is likely to be fully eroded within the next 30 years.

Markers of malignant prostate cancer cells: Golgi localization of α-mannosidase 1A at GM130-GRASP65 site and appearance of high mannose N-glycans on cell surface.

The ability to distinguish malignant from indolent prostate cancer cells is critically important for identification of clinically significant prostate cancer to minimize unnecessary overtreatment and sufferings endured by patients who have indolent cancer. Recently, we discovered that loss of giantin function as the primary Golgi targeting site for endoplasmic reticulum-derived transport vesicles in aggressive prostate cancer cells caused a shift of the Golgi localization site of α-mannosidase 1A to 130 KDa Golgi matrix protein (GM130)-65 KDa Golgi reassembly-stacking protein (GRASP65) site resulting in emergence of high mannose N-glycans on trans-Golgi enzymes and cell surface glycoproteins. To extend this observation, we isolated two cell clones (Clone 1 and Clone 2) from high passage LNCaP cells, which exhibited androgen refractory property missing in low passage LNCaP cells, and characterized their malignant property. We have found that comparing to Clone 2, which does not have cell surface high mannose N-glycans and exhibits localization of α-mannosidase 1A at giantin site, Clone 1 displays cell surface high mannose N-glycans, exhibits localization of α-mannosidase 1A at GM130-GRASP65 site, and shows a faster rate of closing the wound in a wound healing assay. The results indicate that Golgi localization of α-mannosidase 1A at GM130-GRASP65 site and appearance of cell surface high mannose N-glycans may serve as markers of malignant prostate cancer cells.

Molecular "Building Block" and "Side Chain Engineering": Approach to Synthesis of Multifunctional and Soluble Poly(pyrrole phenylene)s.

Here, the synthesis of a novel poly(pyrrole phenylene) (PpyP) that is both modular in ways of functionalization and soluble in organic solvents is reported, and therefore solution processable. This is achieved through the functionalization of the side-chain substituents in pyrrole phenylene (PyP) repeating units. t Butyl acrylate brushes are first grafted through atom transfer radical polymerization from one type of PyP, followed by oxidative chemical co-polymerization of the grafted PyP with a PyP bearing different side chains-either an azide or a methoxy moiety, resulting in a soluble PpyP where solubility is not dopant-dependent. Successful post-polymerization modification through "click" chemistry and post-polymerization processing via electrospinning are also demonstrated. Additionally, performed computational calculations indicate planarity of the novel polyrrole phenylene monomers and ionisation potentials that favor α-α bond formation during their polymerization.

Modular Synthesis and Biological Investigation of 5-Hydroxymethyl Dibenzyl Butyrolactones and Related Lignans.

Dibenzyl butyrolactone lignans are well known for their excellent biological properties, particularly for their notable anti-proliferative activities. Herein we report a novel, efficient, convergent synthesis of dibenzyl butyrolactone lignans utilizing the acyl-Claisen rearrangement to stereoselectively prepare a key intermediate. The reported synthetic route enables the modification of these lignans to give rise to 5-hydroxymethyl derivatives of these lignans. The biological activities of these analogues were assessed, with derivatives showing an excellent cytotoxic profile which resulted in programmed cell death of Jurkat T-leukemia cells with less than 2% of the incubated cells entering a necrotic cell death pathway.

Establishing a High-Yielding Cell-Free Protein Synthesis Platform Derived from Vibrio natriegens.

A new wave of interest in cell-free protein synthesis (CFPS) systems has shown their utility for producing proteins at high titers, establishing genetic regulatory element libraries ( e.g., promoters, ribosome binding sites) in nonmodel organisms, optimizing biosynthetic pathways before implementation in cells, and sensing biomarkers for diagnostic applications. Unfortunately, most previous efforts have focused on a select few model systems, such as Escherichia coli. Broadening the spectrum of organisms used for CFPS promises to better mimic host cell processes in prototyping applications and open up new areas of research. Here, we describe the development and characterization of a facile CFPS platform based on lysates derived from the fast-growing bacterium Vibrio natriegens, which is an emerging host organism for biotechnology. We demonstrate robust preparation of highly active extracts using sonication, without specialized and costly equipment. After optimizing the extract preparation procedure and cell-free reaction conditions, we show synthesis of 1.6 ± 0.05 g/L of superfolder green fluorescent protein in batch mode CFPS, making it competitive with existing E. coli CFPS platforms. To showcase the flexibility of the system, we demonstrate that it can be lyophilized and retain biosynthesis capability, that it is capable of producing antimicrobial peptides, and that our extract preparation procedure can be coupled with the recently described Vmax Express strain in a one-pot system. Finally, to further increase system productivity, we explore a knockout library in which putative negative effectors of CFPS are genetically removed from the source strain. Our V. natriegens-derived CFPS platform is versatile and simple to prepare and use. We expect it will facilitate expansion of CFPS systems into new laboratories and fields for compelling applications in synthetic biology.

Total Synthesis of (-)-Bicubebin A, B, (+)-Bicubebin C and Structural Reassignment of (-)-cis-Cubebin.

The first total synthesis of (-)-bicubebin A, and two previously unreported dilignans, (-)-bicubebin B and (+)-bicubebin C has been achieved through the dimerization of (-)-cubebin, confirming the structure and absolute stereochemistry of (-)-bicubebin A. Analysis of the data for (-)-bicubebin B showed it matched that of reported compound (-)-cis-cubebin. The NMR data of the subsequently synthesized proposed structure of cis-cubebin confirmed that its original proposed structure was incorrect.

Total Synthesis of Ovafolinins†A and B: Unique Polycyclic Benzoxepin Lignans through a Cascade Cyclization.

Ovafolinins A and B, isolated from Lyonia ovalifolia var. elliptica, are lignans that contain a unique bridged structure containing a penta- and tetracyclic benzoxepin and an aryl tetralin. We report the first total synthesis of these natural products in which an acyl-Claisen rearrangement was initially utilized to construct the lignan backbone with correct relative stereochemistry. Judicious use of a bulky protecting group placed reactive moieties in the correct orientation, thereby resulting in a cascade reaction to form the bridged benzoxepin/aryl tetralin from a linear precursor in a single step. Modification of this route allowed the enantioselective synthesis of (+)-ovafolinins A and B, which confirmed the absolute stereochemistry, and comparison of optical rotation suggests that these compounds are found as scalemic mixtures in nature.

Early structural status of the eyes of healthy term neonates conceived by in vitro fertilization or conceived naturally.

PURPOSE: To evaluate the effects of in vitro fertilization (IVF) on early development of the eye in full-term healthy infants. METHODS: A case-control study was performed. The study sample included full-term infants born from March 1 to August 14, 2006, in the Neonatal Department of Helen Schneider Women's Hospital, Rabin Medical Center. Data were collected on sex, gestational age, birth weight, Apgar score, head circumference, body length, and mode of conception (IVF/natural). A full ophthalmologic examination was performed, including measurement of intraocular pressure, keratometry, ultrasound biometry, pachymetry, and funduscopy. RESULTS: Sixty-six infants (132 eyes) were examined; 32 were conceived by IVF, and 34 were conceived naturally. Girls accounted for 56% of the IVF group and 44% of the natural conception group. There were no statistically significant differences between the groups in sex, gestational age, head circumference, intraocular pressure, axial length, anterior chamber depth, and lens thickness. The IVF infants had lower birth weight and body length than the infants born by natural conception (P = 0.032, t-test). Their keratometric and pachymetric values were also higher, but when birth weight and length were controlled, this difference remained statistically significant only for infants with a birth weight of less than 3000 g and a body length of less than 48.5 cm. CONCLUSIONS: IVF apparently has no effect on early development of the eyes in full-term infants. The steeper corneal curvature and greater central corneal thickness in a subset of smaller IVF infants may reflect delayed corneal maturation.