Coupling and uncoupling of midline morphogenesis and cell flow in amniote gastrulation.

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called 'polonaise movements', appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Cellular flows initiate left-right patterning prior to laterality gene expression in amniotes.

A bilateral body plan is predominant throughout the animal kingdom. Bilaterality of amniote embryos becomes recognizable as midline morphogenesis begins at gastrulation, bisecting an embryonic field into the left and right sides. Soon after, left-right asymmetry also starts. While a series of laterality genes expressed after the left-right compartmentalization has been extensively studied, the laterality patterning prior to and during midline morphogenesis has remained unclear. Here, through a biophysical quantification in a high spatial and temporal resolution, applied to a chick model system, we show that a large-scale bilateral counter-rotating cell flow, termed as 'polonaise movements', display left-right asymmetries in early gastrulation. This cell movement starts prior to the formation of the primitive streak, which is the earliest midline structure, and earlier than expression of laterality genes. The cell flow speed and vorticity unravel the location and timing of the left-right asymmetries. The bilateral cell flow exhibited a Left side asymmetry at the beginning, but a transition towards Right dominance. Mitotic arrest that diminishes primitive streak formation resulted in changes in the bilateral flow pattern, but the Right dominance persisted. Our data indicate that the left-right asymmetry in amniote gastrula becomes detectable prior to the point when the asymmetric regulation of the laterality signals at the node leads to the left-right patterning. More broadly, our results suggest that physical processes can play an unexpected but significant role in influencing left-right laterality during embryonic development.

RevCore thrombectomy system for treatment of chronic left external and common iliac vein stent occlusion.

In recent years, deep venous stenting has increasingly become a treatment strategy for post-thrombotic syndrome. Stent thrombosis can occur, resulting in symptom recurrence despite medical therapy, and there are few options available for durable stent patency restoration. We present a case of a 50-year-old male with prior iliocaval reconstruction that experienced recurrent left lower extremity swelling secondary to occlusion of left external iliac and common iliac vein stents during follow-up. Mechanical thrombectomy with the RevCore System and angioplasty was performed. One month later, the patient demonstrated widely patent bilateral iliac vein stents and complete symptomatic resolution. The RevCore System is a feasible alternative for treatment of chronic in-stent thrombosis.

Extensive iliofemoral and femoropopliteal venous thrombosis in a young patient with iliocaval atresia.

Inferior vena cava (IVC) atresia is a rare congenital anomaly. Standardized treatment is not well defined due to its uncommon presentation, with this pathology associated with an increased risk of unprovoked lower extremity deep vein thrombosis (DVT). We present a case of a 32-year-old man who was admitted for bilateral lower extremity edema and pain and was found to have bilateral extensive iliofemoral and femoropopliteal DVT, absence of IVC filling, and extensive tortuous collateralization arising from the pelvic veins to the azygos vein. Bilateral mechanical thrombectomy and endovascular iliocaval reconstruction was performed. Three months later, the patient demonstrated widely patent iliocaval stents and the absence of DVT. Endovascular treatment of IVC atresia is feasible and optimizes the reduction of thrombus burden.

Unleashing the binding interaction of chrysin-Cu(II) complex with the biomacromolecular targets: further studies of cell cytotoxicity and radical scavenging properties.

Flavonoids are significant dietary components and have ability to coordinate with metal ions to produce novel drug discovery leads that are superior to those of the parent flavonoids. Here, in this report, we have synthesized chrysin-Cu(II) complex (as per reported article) and characterized it further with different analytical techniques. The synthesized complex was evaluated for radical scavenging and cell cytotoxicity studies where it exhibited enhanced activity as compared to bare chrysin. The interaction studies of the complex with ct-DNA (Kb ⁓ 105 M-1), human serum albumin (HSA) and ovalbumin (Kb ⁓ 104 M-1) were evaluated using multi-spectroscopic and molecular docking studies. Groove binding mode with ct-DNA was observed as confirmed from competitive displacement studies, viscosity measurement, melting temperature estimation and docking analyses. The complex exhibited comparatively higher affinity towards ct-DNA which indicated it efficient transportation by the carrier proteins and controlled release in the target DNA.Communicated by Ramaswamy H. Sarma.

Coupling and uncoupling of midline morphogenesis and cell flow in amniote gastrulation.

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called 'polonaise movements', appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Acute limb ischemia secondary to bullet embolism following a cardiac gunshot wound in a pediatric patient.

Bullet embolism following a gunshot wound to the heart is a very unusual cause of acute limb ischemia. We report the case of a 3-year-old boy who sustained a penetrating cardiac trauma secondary to an accidental self-inflicted gunshot wound with a BB (ball bearing) gun. The BB pellet entered the left ventricle and embolized into the peripheral circulation, lodging at the bifurcation of the left common femoral artery. This resulted in acute left lower extremity ischemia. The patient was successfully treated by open common femoral artery exploration and foreign body removal.

Superior mesenteric artery aneurysm endovascular repair.

Superior mesenteric artery aneurysms are rare and associated with high mortality rates in cases of rupture. Current Society for Vascular Surgery guidelines recommend treatment of all superior mesenteric artery aneurysms regardless of size. A 53-year-old woman who was admitted for abdominal pain was found with a 14-cm, ruptured superior mesenteric artery branch aneurysm. Endovascular approach was performed with microvascular plug embolization of a feeding branch and aneurysm sac exclusion with a stent graft. Four months later, the patient demonstrated a 21% regression of the aneurysm and stent patency. Thus, timely diagnosis and treatment of superior mesenteric artery aneurysms with endovascular techniques can reduce potential complications.

Kommerell's Diverticulum in a Right-Sided Aortic Arch With an Aberrant Left Subclavian Artery Hybrid Repair.

BACKGROUND: Kommerell's diverticulum (KD) with a right aortic arch (RAA) and aberrant left subclavian artery (aLSCA) is a rare congenital anomaly of the aortic arch. Treatment is not well defined due to its uncommon presentation, with rupture and dissection risk rates of up to 53%. CASE SUMMARY: A 54-year-old male with a history of chronic obstructive pulmonary disease (COPD) and hypertension presented with difficulty breathing during exercise without dysphagia. Follow-up computerized tomography angiogram (CTA) revealed the presence of a RAA and aLSCA arising from the descending thoracic aorta with an adjacent 58 × 41-mm KD and tracheal and esophageal displacement. Due to the size of the KD, risk of rupture, unsuitable anatomy for total endovascular aortic repair (EVAR), and high COPD burden, the patient was planned to undergo a hybrid surgical repair. Left common carotid (LCCA) artery to LSCA bypass, full aortic debranching, LSCA embolization and percutaneous thoracic endovascular aortic repair (TEVAR) were performed. Successful device position and exclusion of the diverticulum and aneurysmal aorta were observed after completion thoracic aortogram. 18-month follow-up CTA demonstrated patency of the LSCA to LCCA bypass graft and arch vessel branches, as well as stable exclusion of the KD. Persistence of a type II endoleak originated at the right first posterior intercostal artery has been noted and is being followed conservatively since no sac growth has occurred. CONCLUSION: We highlight the presence of a KD with RAA and aberrant subclavian artery, a rare congenital anatomic variation of the aortic arch with complex anatomy. Surgical planning must be individualized according to comorbidities and anatomical variations identified on imaging and 3D reconstructions.

Non-Bilaterians as Model Systems for Tissue Mechanics.

In animals, epithelial tissues are barriers against the external environment, providing protection against biological, chemical, and physical damage. Depending on the organism's physiology and behavior, these tissues encounter different types of mechanical forces and need to provide a suitable adaptive response to ensure success. Therefore, understanding tissue mechanics in different contexts is an important research area. Here, we review recent tissue mechanics discoveries in three early divergent non-bilaterian systems-Trichoplax adhaerens, Hydra vulgaris, and Aurelia aurita. We highlight each animal's simple body plan and biology and unique, rapid tissue remodeling phenomena that play a crucial role in its physiology. We also discuss the emergent large-scale mechanics in these systems that arise from small-scale phenomena. Finally, we emphasize the potential of these non-bilaterian animals to be model systems in a bottom-up approach for further investigation in tissue mechanics.

Efficient Biosorption of Hexavalent Chromium from Water with Human Hair.

The triphenyl group (trityl radical) possessing three-phenyl rings, self-assembled through aromatic π-π stacking interactions, can form interesting crystalline organic nano-flowers. In this work, we have synthesized a hybrid material of 1,2-bis(tritylthio)ethane and magnetite, which reduces toxic Cr(VI) to non-toxic Cr(III). We validated the efficacy of the hybrid in reducing toxic Cr(VI) along with three other adsorbent systems. Among the five adsorbent systems tested, we observed that human hair has higher Cr removal efficiency, which prompted us to explore further using different mechanical forms of human hair. Pulverized hair (PH), hair powder (HP), and raw hair (RH) were evaluated by employing different reaction factors such as the adsorbent dose, pH, initial Cr(VI) concentration, and contact time. The comparative evaluation showed that PH has greater adsorption capacity (15.14 mg/g), followed by RH (13.27 mg/g) and HP (10.5 mg/g). While investigating the adsorption mechanism, we observed that it follows pseudo-second-order kinetics suggesting chemisorption. The Freundlich isotherm model fitted well for Cr(VI) adsorption by human hair, suggesting a multi-layered adsorption process. Overall, this study promises a cost-effective and eco-friendly bio-adsorbent for Cr(VI), which may be scaled up to design automated industrial waste disposal systems.

Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes.

Most motile cilia have a stereotyped structure of nine microtubule outer doublets and a single central pair of microtubules. The central pair of microtubules are surrounded by a set of proteins, termed the central pair apparatus. A specific kinesin, Klp1 projects from the central pair and contributes to ciliary motility in Chlamydomonas. The vertebrate ortholog, Kif9, is required for beating in mouse sperm flagella, but the mechanism of Kif9/Klp1 function remains poorly defined. Here, using Xenopus epidermal multiciliated cells, we show that Kif9 is necessary for ciliary motility and the proper distal localization of not only central pair proteins, but also radial spokes and dynein arms. In addition, single-molecule assays in vitro reveal that Xenopus Kif9 is a long-range processive motor, although it does not mediate long-range movement in ciliary axonemes in vivo. Together, our data suggest that Kif9 is integral for ciliary beating and is necessary for proper axonemal distal end integrity.

Coral physiology: Going with the ciliary flow.

Corals have long been known to generate local fluid flows using ciliary beating, but the importance of these ciliary flows is just being discovered. Two new papers shed light on how ciliary-flow physics plays a key role in shaping coral physiology.

Antibacterial hydrogels of aromatic tripeptides.

Self-assembled peptide hydrogels have emerged as alternatives to the conventional approaches employed in controlled drug release, wound-healing, and drug delivery, and as anti-infective agents. However, peptide hydrogels possessing antibacterial properties are less explored. In this work, we have designed three ultrashort antibacterial peptide hydrogels: Fmoc-FFH-CONH2, Fmoc-FHF-CONH2, and Fmoc-HFF-CONH2. The rheological study showed the higher storage modulus of Fmoc-FFH-CONH2 (30.43 kPa) compared to Fmoc-FHF-CONH2 and Fmoc-HFF-CONH2, which may be attributed to the enhanced aromatic interaction in Fmoc-FFH-CONH2 compared to the other two variants, resulting in more mechanical rigidity. Further, the prepared hydrogels were evaluated for their inherent antibacterial potency against Gram-positive (Staphylococcus aureus, strain MTCC 96) and Gram-negative (Pseudomonas aeruginosa, strain PA01) bacteria. Antibacterial experiments demonstrated the potency of the hydrogels in the order of Fmoc-FFH-CONH2 > Fmoc-FHF-CONH2 > Fmoc-HFF-CONH2. The antibacterial effect of the hydrogels was predominantly due to the osmotic stress and membrane disruption, which was verified by reactive oxygen species (ROS) generation and outer membrane permeabilization assays. Our findings point to the scope of using the synthesized peptide hydrogels as agents for topical applications.

Outcomes following Placement and Removal of Transvaginal Cerclage in at Risk Pregnancies: A Single Center Experience.

Objective: The objective of this study was to estimate the time between removal of cerclage and delivery, stratified by indication for cerclage placement (elective or non-elective). Additionally, delivery within 72 hours after cerclage removal was compared between elective and non-elective cerclage placement, as well as between ultrasound-indicated and physical examination-indicated cerclage placement. Design: A single-center retrospective cohort study. Participants/Materials, Setting, and Methods. Clinical information of 72 pregnant women who underwent transvaginal cerclage over a 4-year period was obtained. Comparisons were made between elective (history-indicated) and non-elective (ultrasound or physical examination-indicated) cerclage placement. Comparisons were also made between physical examination-indicated and ultrasound-indicated cerclage. Results: Compared to those who had a non-elective cerclage, women undergoing elective cerclage were more likely to have history of cervical treatment (44% vs. 15%, p = 0.02), and spontaneous preterm delivery (92% vs. 61%, p = 0.003). There was no difference in the rate of delivery ≤72 hours following cerclage removal between women who had elective cerclage and those who had non-elective cerclage (46% vs. 58%, p = 0.47). Women who had an elective cerclage were more likely to have elective cerclage removal ≥36 weeks (71.8% vs. 39.4%, p = 0.01), compared to those who had undergone non-elective cerclage. The rate of delivery ≤72 hours following removal of cerclage was greater in women who had a physical examination-indicated cerclage compared to women who had ultrasound-indicated cerclage (80% vs. 39%, p = 0.04). Among women who had an elective cerclage, there was no difference in the rate of delivery at ≤72 hours between those who had elective cerclage removal at 36 weeks compared to those electively removed at 37 weeks (31% vs. 58%, p = 0.30). No complications such as fetal demise, iatrogenic amniotic membrane rupture, hemorrhage, or cervical laceration were reported within this cohort. Conclusion: Cerclage indication should be considered prior to scheduling elective cerclage removal. Women who had an elective cerclage are most likely to get it electively removed at 36 weeks compared to their counterparts who had a non-elective cerclage. Furthermore, women who had a physical examination-indicated cerclage are most likely to deliver within 72 hours of cerclage removal.

Syndiotactic hexamer peptide nanodots.

Spatial confinement of excitons in the nano-crystalline region of semiconducting nanostructures differ significantly from the optoelectronic properties exhibited by the bulk material. We report spike-like absorption observed in the UV spectrum of a phenylalanine hexamer peptide [(Ff)3-OH] nano-assembly, which may be attributed to the spatial confinement of electrons to the dimension of quantum dots. Interdependency of the UV and PLE spectrum of the peptide confirms the existence of quantum confinement in (Ff)3-OH nano-assemblies.

Influence of Obesity on Blood Pressure Responses to Antihypertensive Drug Therapy in an Urban Hypertension Specialty Clinic.

BACKGROUND: Previous studies have reported that lean hypertensives have worse clinical outcomes than obese hypertensives as obesity confers pharmacological resistance to antihypertensive therapy. We explored whether the higher prescribed doses of antihypertensives in obese hypertensives were adequate for the attainment of similar on-treatment blood pressure (BP) versus leaner hypertensives. METHODS: A retrospective chart review of predominantly African American females from a deidentified urban referral clinic was conducted (N = 851; median follow-up = 11.3 months). Body mass index (BMI, kg/m2) was categorized as either below or above or equal to 30. Antihypertensive therapeutic intensity score (TIS) was calculated as the total daily antihypertensive dose/maximum United States Food and Drug Administration (USFDA) approved daily dose, summed across all hypertensive drugs. General linear models were used to estimate the significance of continuous variables across BMI categories. RESULTS: At baseline, systolic blood pressure (SBP) was similar between groups (P = 0.14), though 2.7 mm Hg higher in the highest BMI group. Antihypertensive TIS was greater in the highest BMI category at both baseline and end of follow-up (both P < 0.001). After covariate adjustment end of follow-up SBP and diastolic blood pressure was higher in the obese group by 3.4 (0.6-6.1) and 1.8 (0.1-3.53) mm Hg, respectively (P = 0.02, P = 0.04). CONCLUSIONS: Attained on-treatment BP is higher in obese than non-obese hypertensives despite greater prescription of antihypertensive medications. Whether even more prescription of medications or other interventions will equalize BP responses relative to non obese hypertensives merits further study.

The Effect of COVID-19 on Training and Case Volume of Vascular Surgery Trainees.

BACKGROUND: In many facilities, the coronavirus disease (COVID-19) pandemic caused suspension of elective surgery. We therefore sought to determine the impact of this on the surgical experience of vascular trainees. METHODS: Surgical case volume, breadth, and the participating trainee post-graduate level from 3 large New York City Hospitals with integrated residency and fellowship programs (Mount Sinai, Montefiore Medical Center/Albert Einstein College of Medicine, and New York University) were reviewed. Procedures performed between February 26 to March 25, 2020 (pre-pandemic month) and March 26 to April 25, 2020 (peak pandemic period) were compared to those performed during the same time period in 2019. The trainees from these programs were also sent surveys to evaluate their subjective experience during this time. RESULTS: The total number of cases during the month leading into the peak pandemic period was 635 cases in 2019 and 560 cases in 2020 (12% decrease). During the peak pandemic period, case volume decreased from 445 in 2019 to 114 in 2020 (74% reduction). The highest volume procedures during the peak pandemic month in 2020 were amputations and peripheral cases for acute limb ischemia; during the 2019 period, the most common cases were therapeutic endovascular procedures. There was a decrease in case volume for vascular senior residents of 77% and vascular junior and midlevel residents of 75%. There was a 77% survey response rate with 50% of respondents in the senior years of training. Overall, 20% of respondents expressed concern about completing ACGME requirements due to the COVID-19 pandemic. CONCLUSIONS: Vascular surgery-specific clinical educational and operative experiences during redeployment efforts have been limited. Further efforts should be directed to quantify the impact on training and to evaluate the efficacy of training supplements such as teleconferences and simulation.

Adverse Health Outcomes Associated With Refractory and Treatment-Resistant Hypertension in the Chronic Renal Insufficiency Cohort.

Refractory hypertension (RfH) is a severe phenotype of antihypertension treatment failure. Treatment-resistant hypertension (TRH), a less severe form of difficult-to-treat hypertension, has been associated with significantly worse health outcomes. However, no studies currently show how health outcomes may worsen upon progression to RfH. RfH and TRH were studied in 3147 hypertensive participants in the CRIC (Chronic Renal Insufficiency Cohort study). The hypertensive phenotype (ie, no TRH or RfH, TRH, or RfH) was identified at the baseline visit, and health outcomes were monitored at subsequent visits. Outcome risk was compared using Cox proportional hazards models with time-varying covariates. A total of 136 (4.3%) individuals were identified with RfH at baseline. After adjusting for participant characteristics, individuals with RfH had increased risk for the composite renal outcome across all study years (50% decline in estimated glomerular filtration rate or end-stage renal disease; hazard ratio for study years 0-10=1.73 [95% CI, 1.42-2.11]) and the composite cardiovascular disease outcome during later study years (stroke, myocardial infarction, or congestive heart failure; hazard ratio for study years 0-3=1.25 [0.91-1.73], for study years 3-6=1.50 [0.97-2.32]), and for study years 6-10=2.72 [1.47-5.01]) when compared with individuals with TRH. There was no significant difference in all-cause mortality between those with refractory versus TRH. We provide the first evidence that RfH is associated with worse long-term health outcomes compared with TRH.

De Novo Designed Heterochiral Blue Fluorescent Protein.

Diversification of chain stereochemistry offers a tremendous increase in protein design space. We have designed a minimal fluorescent protein, pregnant with ß-(1-azulenyl)-l-alanine in the hydrophobic core of a heterotactic protein scaffold, employing automated design tools such as automated repetitive simulated annealing molecular dynamics and IDeAS. The de novo designed heterochiral protein can be selectively excited at 342 nm, quite distant from the intrinsic fluorophore, and emits in the blue region. The structure and stability of the designed proteins were evaluated by established spectroscopic and calorimetric methods.