Nuclear sorting of short RNA polymerase II transcripts.

Mammalian genomes produce an abundance of short RNA. This is, to a large extent, due to the genome-wide and spurious activity of RNA polymerase II (RNAPII). However, it is also because the vast majority of initiating RNAPII, regardless of the transcribed DNA unit, terminates within a ∼3-kb early "pausing zone." Given that the resultant RNAs constitute both functional and non-functional species, their proper sorting is critical. One way to think about such quality control (QC) is that transcripts, from their first emergence, are relentlessly targeted by decay factors, which may only be avoided by engaging protective processing pathways. In a molecular materialization of this concept, recent progress has found that both "destructive" and "productive" RNA effectors assemble at the 5' end of capped RNA, orchestrated by the essential arsenite resistance protein 2 (ARS2) protein. Based on this principle, we here discuss early QC mechanisms and how these might sort short RNAs to their final fates.

Pulmonary Overcirculation Requiring Surgical and Pulmonary Flow Restrictor Device Intervention in Critical Coarctation of the Aorta-A Case Series.

The use of prostaglandin infusion to maintain patency of the ductus arteriosus in patients with critical coarctation of the aorta (CoA) to support systemic circulation is the standard of care. However, pulmonary overcirculation resulting from a patent ductus arteriosus in patients with critical CoA is not well described in the literature. We report two cases of critical CoA that required invasive measures to control pulmonary blood flow before surgical repair of the CoA. Both patients had signs of decreased oxygen delivery, hyperlactatemia, and systemic to pulmonary flow via the ductus arteriosus. One patient required surgical pulmonary artery banding and the second patient underwent pulmonary flow restrictor device placement for the control of pulmonary blood flow. A rapid improvement in oxygen delivery and normalization of lactate levels were observed after control of pulmonary overcirculation. Both patients underwent successful surgical repair of the coarctation A and were discharged home.

Novel Staged Device Occlusion of Portosystemic Shunt With Atrial Flow Regulator in IVC Stent Platform.

We present the cases of 2 children diagnosed with extrahepatic portosystemic shunts, a very rare vascular anomaly, on investigation of cardiac symptomatology. Poorly developed portal venous systems necessitated staged shunt occlusion. This was achieved using atrial flow regulator devices positioned in an inferior vena cava stent platform performed in the cardiac catheterization laboratory.

ZC3H4/Restrictor Exerts a Stranglehold on Pervasive Transcription.

The regulation of transcription by RNA polymerase II (RNAPII) underpins all cellular processes and is perturbed in thousands of diseases. In humans, RNAPII transcribes ∼20000 protein-coding genes and engages in apparently futile non-coding transcription at thousands of other sites. Despite being so ubiquitous, this transcription is usually attenuated soon after initiation and the resulting products are immediately degraded by the nuclear exosome. We and others have recently described a new complex, "Restrictor", which appears to control such unproductive transcription. Underpinned by the RNA binding protein, ZC3H4, Restrictor curtails unproductive/pervasive transcription genome-wide. Here, we discuss these recent discoveries and speculate on some of the many unknowns regarding Restrictor function and mechanism.

Use of Flow Restrictors in Congenital Heart Disease.

The surgical pulmonary artery band was first introduced in 1952 and, to this day, can produce challenges in regard to the ideal amount of restriction and the need for reoperations. A transcatheter option may be the ideal solution as it allows for a less-invasive approach for a better hemodynamic assessment and easier re-intervention. To date, multiple approaches have been developed with device modifications to create restrictions to flow, each with advantages and limitations. Continued experience is still necessary to determine the ideal device to use to create an adequate and modifiable level of restriction.

Creating a flow restrictor in ductal stenting: a novel technique.

Ductal stenting has transformed the care of neonates with ductal-dependent critical CHD, especially in low-income countries. In small infants, a 3.5- or 4-mm stent may lead to too much pulmonary blood flow resulting in pulmonary oedema. We herein presented a novel technique to restrict ductal stent flow in a premature neonate with pulmonary atresia and intact ventricular septum following radiofrequency perforation of the pulmonary valve.

Comparison of osteolysis around 3 different cement restrictors in total hip arthroplasty.

BACKGROUND AND AIM: Several studies reported osteolysis around polyethylene glycol/polybutylene terephthalate (PEG/PBT) based femoral cement restrictors. Our goal was to evaluate and compare osteolysis around 3 different plug designs: the slow biodegradable PEG/PBT cement restrictor; the fast biodegradable gelatin cement restrictor; and the non-biodegradable polyethylene plug. PATIENTS AND METHODS: In a retrospective multicentre cohort study chart data were extracted of patients who received a total hip arthroplasty between 2008 and 2012. A total of 961 hips were included. Cortical ratio between inner and outer cortices at the centre of the plug was measured on routine postoperative follow-up moments. Median follow up of all 3 hospitals was 3.5 years (1.4-7.3). The primary outcome was evidence of osteolysis (i.e. the difference in cortical ratio [CR]) on anteroposterior (AP) radiographs at final follow-up. RESULTS: Progressive osteolysis was found around the PEG/PBT cement restrictor represented by a significantly increasing cortical ratio (ΔCR 0.067 (95% CI, 0.063-0.071). Distance from tip prosthesis to plug and size of the plug were found to be independent factors in predicting increased cortical ratio. CONCLUSIONS: Our multicentre cohort shows increase of cortical ratio around the PEG/PBT cement restrictor which progresses over time. Physicians should be aware of this fact and are advised to intensify follow-up of patients who received this cement restrictor.

Outcomes of manually modified microvascular plugs to pulmonary flow restrictors in various congenital heart lesions.

Background: The development of microvascular plugs (MVPs) has enabled novel transcatheter deliverable endoluminal pulmonary flow restrictors (PFRs) with the potential to treat newborns and infants with life-threatening congenital heart diseases (CHDs) in a minimally invasive manner. We present our experience to evaluate the efficacy of this concept in controlling pulmonary blood flow in various CHDs. Methods: Retrospective clinical data review of patients with CHD and pulmonary over-circulation who received bilateral PFRs percutaneously. Results: Twenty-eight PFRs (7 MVP-5Q, 12 MVP-7Q, and 9 MVP-9Q) were finally implanted in 14 patients with a median age of 1.6 months (IQR, 0.9-2.3) and a median weight of 3.1 Kg (IQR, 2.7-3.6). Nine patients had large intra-cardiac left-to-right shunts (including 3 with fatal trisomy and palliative programs), 2 had borderline left ventricles, 2 had Taussig-Bing anomaly, and one had a hypoplastic left heart. Four patients had concomitant ductal stenting. Two MVP-5Qs were snare-removed and upsized to MVP-7Q. Patients experienced a significant drop in oxygen saturation and Qp/Qs. All patients were discharged from the ICU after a median of 3.5 days (IQR, 2-5.8) postoperative. Five patients had routine inter-stage catheterization and no device embolization or pulmonary branch distortion was seen. Fourteen (50%) PFRs were surgically explanted uneventfully on a median of 4.3 months (IQR, 1.2-6) post-implantation during biventricular repair in 6 patients and stage-2 palliation in one patient. The latter died 1 month post-operative from severe sepsis. Four patients are scheduled for surgical PFR removal and biventricular repair. Two patients with trisomy 18 died at 1 and 6.8 months post-procedure from non-cardiac causes. One patient with trisomy 13 is alive at 2.7 months post-procedure. Conclusion: It is feasible to bespoke MVPs and implant them as effective PFRs in various CHDs. This approach enables staged left ventricular recruitment, comprehensive stage-2 or biventricular repair with lower risk by postponing surgeries to later infancy. Device explantation is uneventful, and the outcomes afterward are promising.

Effect of Novel Gastro-Duodenal Flow Restrictor on Relative Weight Loss and Glucose Levels in a Porcine Model: A Pilot Randomized Study.

Endoscopic bariatric and metabolic therapies are promising for obesity. We developed a novel gastro-duodenal flow restrictor (G-DFR) device for relative weight loss and lowering of glucose level and evaluated its safety and efficacy in a porcine model. The G-DFR comprised self-expandable gastro-duodenal partially covered polytetrafluoroethylene (PTFE) metal stent distally attached to a PTFE skirt. Eleven juvenile pigs were randomized into the evaluation of migration (n = 3), mid-term efficacy (n = 5), and control (n = 3) groups. Five pigs showed G-DFR migration at 2, 4, 7, and 10 weeks after placement in the migration and mid-term efficacy group. Compared to the control group, the mid-term efficacy group showed up to 55.4% relative weight loss in 12 weeks. Compared to the case group, the control group showed higher mean ghrelin hormone level from 6 to 12 weeks. Glucose level was significantly lower in the efficacy group than in the control group after 6 weeks. Serum alanine transferase levels and histological collagen deposition were lower in the liver of the case group than in the control group. Although it did not demonstrate consistent performance with respect to migration, a well-positioned G-DFR in the pyloroduodenal portion may lead to relative weight loss, lowering of glucose levels, and improved hepatic parameters.

Efficacy of cement restrictors: Experimental study and development of a classification. / Eficacia de los restrictores de cemento: estudio experimental y desarrollo de una clasificación.

INTRODUCTION: Cement restrictors (CRs) are devices that allow occlusion of the femoral canal in order to obtain greater interdigitation of the cement between the bone and a better pressurization, which generates an increase in the survival of cemented stems. The aim of this study was to evaluate the efficacy of the different CRs used and propose a classification of this device. MATERIALS AND METHODS: An experimental study was carried out, where 7 CR references of different designs and manufacturers were taken. Later, tests were carried out on 9 chlorinated polyvinyl chloride tubes for each reference, to achieve a total of 63 tests. RESULTS: In our study, 34.9% of the CRs in ultra high molecular weight polyethylene failed, presenting migration and allowing cement to leak while none of the gelatin RC failed. CONCLUSION: The RC with an umbrella design proved to be the less effective, presented a higher incidence of migration and cement leakage, while the gelatin CRs were the best performers. Based on the results of this study, an analysis of the CR design was carried out and a classification was proposed that divides these devices into 2 types.

Efficacy of cement restrictors: Experimental study and development of a classification / Eficacia de los restrictores de cemento: estudio experimental y desarrollo de una clasificación

Introduction: Cement restrictors (CRs) are devices that allow occlusion of the femoral canal in order to obtain greater interdigitation of the cement between the bone and a better pressurization, which generates an increase in the survival of cemented stems. The aim of this study was to evaluate the efficacy of the different CRs used and propose a classification of this device. Materials and methods: An experimental study was carried out, where 7 CR references of different designs and manufacturers were taken. Later, tests were carried out on 9 chlorinated polyvinyl chloride tubes for each reference, to achieve a total of 63 tests. Results: In our study, 34.9% of the CRs in ultra high molecular weight polyethylene failed, presenting migration and allowing cement to leak while none of the gelatin RC failed. Conclusion: The RC with an umbrella design proved to be the less effective, presented a higher incidence of migration and cement leakage, while the gelatin CRs were the best performers. Based on the results of this study, an analysis of the CR design was carried out and a classification was proposed that divides these devices into 2 types.(AU)

Introducción: Los restrictores de cemento (RC) son dispositivos que permiten la oclusión del canal femoral con el fin de obtener una mayor interdigitación del cemento en el hueso y una mejor presurización, lo que genera un incremento en la supervivencia de los vástagos cementados. El objetivo de este estudio fue evaluar la eficacia de los diferentes RC utilizados y proponer una clasificación de este dispositivo. Materiales y métodos: Se realizó un estudio experimental, donde se tomaron 7 referencias de RC de diferentes diseños y fabricantes. Posteriormente se hicieron pruebas en 9 tubos de policloruro de vinilo clorado por cada referencia para conseguir un total de 63 pruebas. Resultados: El 34,9% de los RC de nuestro estudio presentaron migración y permitieron la fuga de cemento; todos estos RC eran de polietileno de ultra alto peso molecular (PUAPM), mientras que ninguno de los RC de gelatina falló. Conclusión: Los RC con diseño en paraguas demostraron ser los menos eficaces, presentando una mayor incidencia de migración y fuga de cemento, mientras que los RC de gelatina fueron los de mejor desempeño. Basado en los resultados de este estudio, se realizó un análisis del diseño de los RC y se propuso una clasificación que divide estos dispositivos en 2 tipos.(AU)

Eficacia de los restrictores de cemento: estudio experimental y desarrollo de una clasificación / Efficacy of cement restrictors: Experimental study and development of a classification

Introducción: Los restrictores de cemento (RC) son dispositivos que permiten la oclusión del canal femoral con el fin de obtener una mayor interdigitación del cemento en el hueso y una mejor presurización, lo que genera un incremento en la supervivencia de los vástagos cementados. El objetivo de este estudio fue evaluar la eficacia de los diferentes RC utilizados y proponer una clasificación de este dispositivo. Materiales y métodos: Se realizó un estudio experimental, donde se tomaron 7 referencias de RC de diferentes diseños y fabricantes. Posteriormente se hicieron pruebas en 9 tubos de policloruro de vinilo clorado por cada referencia para conseguir un total de 63 pruebas. Resultados: El 34,9% de los RC de nuestro estudio presentaron migración y permitieron la fuga de cemento; todos estos RC eran de polietileno de ultra alto peso molecular (PUAPM), mientras que ninguno de los RC de gelatina falló. Conclusión: Los RC con diseño en paraguas demostraron ser los menos eficaces, presentando una mayor incidencia de migración y fuga de cemento, mientras que los RC de gelatina fueron los de mejor desempeño. Basado en los resultados de este estudio, se realizó un análisis del diseño de los RC y se propuso una clasificación que divide estos dispositivos en 2 tipos.(AU)

Introduction: Cement restrictors (CRs) are devices that allow occlusion of the femoral canal in order to obtain greater interdigitation of the cement between the bone and a better pressurization, which generates an increase in the survival of cemented stems. The aim of this study was to evaluate the efficacy of the different CRs used and propose a classification of this device. Materials and methods: An experimental study was carried out, where 7 CR references of different designs and manufacturers were taken. Later, tests were carried out on 9 chlorinated polyvinyl chloride tubes for each reference, to achieve a total of 63 tests. Results: In our study, 34.9% of the CRs in ultra high molecular weight polyethylene failed, presenting migration and allowing cement to leak while none of the gelatin RC failed. Conclusion: The RC with an umbrella design proved to be the less effective, presented a higher incidence of migration and cement leakage, while the gelatin CRs were the best performers. Based on the results of this study, an analysis of the CR design was carried out and a classification was proposed that divides these devices into 2 types.(AU)

A computational fluid dynamics assessment of 3D printed ventilator splitters and restrictors for differential multi-patient ventilation.

BACKGROUND: The global pandemic of novel coronavirus (SARS-CoV-2) has led to global shortages of ventilators and accessories. One solution to this problem is to split ventilators between multiple patients, which poses the difficulty of treating two patients with dissimilar ventilation needs. A proposed solution to this problem is the use of 3D-printed flow splitters and restrictors. There is little data available on the reliability of such devices and how the use of different 3D printing methods might affect their performance. METHODS: We performed flow resistance measurements on 30 different 3D-printed restrictor designs produced using a range of fused deposition modelling and stereolithography printers and materials, from consumer grade printers using polylactic acid filament to professional printers using surgical resin. We compared their performance to novel computational fluid dynamics models driven by empirical ventilator flow rate data. This indicates the ideal performance of a part that matches the computer model. RESULTS: The 3D-printed restrictors varied considerably between printers and materials to a sufficient degree that would make them unsafe for clinical use without individual testing. This occurs because the interior surface of the restrictor is rough and has a reduced nominal average diameter when compared to the computer model. However, we have also shown that with careful calibration it is possible to tune the end-inspiratory (tidal) volume by titrating the inspiratory time on the ventilator. CONCLUSIONS: Computer simulations of differential multi patient ventilation indicate that the use of 3D-printed flow splitters is viable. However, in situ testing indicates that using 3D printers to produce flow restricting orifices is not recommended, as the flow resistance can deviate significantly from expected values depending on the type of printer used. TRIAL REGISTRATION: Not applicable.

Total Transcatheter Stage 1: A Word of Caution.

For patients with single ventricle physiology, being able to initially establish systemic blood flow and control pulmonary blood flow is critical to their long-term health. Recently, there have been descriptions in achieving this by a purely transcatheter approach with stenting of the ductus arteriosus and implanting pulmonary flow restrictors, a very appealing prospect. We review a case series of 6 patients who underwent a percutaneous modified stage 1 approach using modified Microvascular plugs (MVP) at our center between September 2019 and December 2019. The initial procedure was technically successful in all patients with single-stage ductal stenting and placement of bilateral modified MVP via femoral access. Four patients underwent repeat cardiac catheterization prior to subsequent surgery that demonstrated elevated Qp:Qs (> 2:1) in 3 of the 4 patients with an elevated mean distal PA pressure > 20 mmHg in all patients. In some patients, the device migrated into the distal right pulmonary artery. One patient after Glenn shunt was found to have significant LPA stenosis requiring stenting. While the percutaneous modified stage 1 approach is a promising approach, we offer a word of caution against widespread adoption of this technique with the currently available devices.

Thorpe tube and oxygen flow restrictor: what's flow accuracy?

Oxygen gas flowmeters (OGF) are used to regulate the oxygen flow in acute and chronic care. In hospitals, Thorpe tubes (TT) are the classical systems most used for delivering oxygen. In recent years, the oxygen flow restrictor (OFR) has appeared. These devices use a series of calibrated openings in a disk that can be adjusted to deliver different flow rates. These devices have a reputation for delivering more accurate oxygen flow rates compared to classical OGFs. However, to our knowledge, few study has examined this supposition. This study aimed to compare and evaluate the accuracy and precision of the ready-to-use TTs and OFRs. OGFs were selected from hospitals in Belgium and France. Before performing the flow measurements, the inlet pressure was checked. The accuracy of the OGF was analyzed with a calibrated thermal mass flowmeter (RED Y COMPACT™ GCM-0 to 20 L/min-VÖGTLIN Instruments). Different flows (2, 4, 6, 9 or 12 L/min) were evaluated. Linear regression analysis, bias (with confidence interval) and lower and upper limit of the agreement were calculated for TTs and OFRs. All measurements are expressed in absolute values. Four-hundred-seventy-six TTs and 96 OFRs were analyzed. The intra-class correlation coefficient calculated for the calibrated thermal mass flowmeter was > 0.99 and reflected the excellent reliability of our measurements. For TTs, the bias value was - 0.24 L/min (± 0.88), and the limits of agreement were - 1.97 to 1.48 L/min. For OFRs, the bias value was - 0.30 L/min (± 0.54), and the limits of agreement were - 1.36 to 0.77 L/min. As the flow increased, the accuracy of all analyzed OGFs decreased. With the increasing flow, some data fell outside the limits of agreement, and the trend increased with the elevated oxygen flow. TTs were less accurate compared to OFRs due to the increased flow variability. However, for TTs and OFRs, as the required flow is elevated, the dispersion of values increases on both sides of the actual flow.

Canal occlusion in cemented primary total hip replacement: autologous compacted bone block compared to a commercially available gelatine plug.

AIMS: To evaluate the stability of 2 canal occlusion systems; an autologous, compacted bone block and the biodegradable C-plug. We also sought to investigate any relationship between stability of the systems and the quality of cementation. A retrospective radiographic comparative review was conducted. METHODS: A total of 203 consecutive patients were analysed, 89 received an autologous bone block and 114 had C-plugs. There was no significant differences between the groups in terms of age, sex and primary diagnosis. The mean cement tail length in the bone block group (6.42 mm; range 0-31) was significantly shorter than in the C-plug group (17.11 mm; range 0-65.7). RESULTS: The proportion of patients with good quality of cementation (Barrack grade A) was significantly higher in the bone block group (80.6%) as compared to the C-plug group (56%) (p < 0.001). There was a negative correlation between the length of the cement tail and the Barrack grade, indicating that a short cement tail is associated with better quality cementation. CONCLUSIONS: We have shown that improved cement penetration and shorter cement tails can be achieved with the cheapest of all options for canal occlusion, an autologous compacted bone block and hence recommend this technique.

Application of a Microsurgical Space Restrictor in Microsurgical Simulation Training.

OBJECTIVE: To investigate the effect of the application of a microsurgical space restrictor in microsurgical simulation training. METHODS: A microsurgical space restrictor that can restrict the operation space was designed and produced. Forty neurosurgery residents with standardized training were selected as the study subjects and were randomly divided into the experimental group (group A) and the control group (group B). Group A was trained using the space restrictor, and group B was trained using the traditional method. The skills and overall performance of the 2 groups of trainees were assessed by the Stanford Microsurgery and Resident Training (SMaRT) scale. The assessment was divided into 2 stages: the unobstructed microsurgery test, and the test with the microsurgical operation space restrictor. RESULTS: In group A, the score for the first stage (A1) was 3.9 ± 0.6, the score for the second stage (A2) was 3.4 ± 0.6, and the score for A1 was better than that for A2 (P = 0.000); in group B, the score for the first stage (B1) was 3.57 ± 0.6, the score for the second stage (B2) was 3.0 ± 0.6, and the score for B1 was better than that for B2 (P = 0.000). Overall, the score for A1 was better than that for B1 (P = 0.046), and the score for A2 was better than that for B2 (P = 0.009). CONCLUSIONS: Microsurgical space restrictor use can improve the effect of microsurgical simulation training and help trainees better master microsurgical operation skills.

Charnley femoral cemented stem with a permeable and resorbable cement restrictor and low-viscosity cement - Clinical and radiographical evaluation of 100 cases at a mean follow-up of 6.55 years.

INTRODUCTION: In 1979, in his first book dealing with low-friction arthroplasty (LFA), Charnley highlighted the use of a cement restrictor. Breusch and Malchau described in 2005 the "second-generation cementing technique." The main objective of this study was to report on the clinical survival of 100 cases of Charnley femoral component implanted in 2007 and 2008 using a permeable and resorbable cement restrictor and a low-viscosity antibiotic-loaded cement. The secondary objectives were to analyze the complications and side effects and the accuracy of the device positioning. MATERIAL AND METHODS: This was a monocentric retrospective review of a prospectively compiled database. Diaphyseal restrictor was biodegradable and permeable to gas, blood, and fluids to avoid intramedullary over pression during cementation. The cement was a low-viscosity antibiotic-loaded cement. Among 3555 patients, we selected the first continuous 100 cases of patients where we implanted the device. Survival probability was computed according to Kaplan-Meier method. RESULTS: Mean follow-up was 6.55 ± 2.6 (range 1-11). Considering femoral component revision as the endpoint, survival rate was 100%. No patients died intraoperatively, none in the first month and the first year after surgery. No early periprosthetic fractures have been reported. DISCUSSION: As described initially by Charnley, the use of a cement restrictor was highly recommended through the different generations of cementing techniques. Hypotensive episodes and cardiac arrest have been reported during cement insertion. In our series, we did not deplore any adverse effect related to the cementation. CONCLUSION: Our study demonstrates a 100% survival rate of a cemented femoral component without adverse effects when using routinely a resorbable and permeable cement restrictor and a low-viscosity cement. Bone cement is still a fantastic ally for the surgeon and the patients.

On-line Analysis of Catalytic Reaction Products Using a High-Pressure Tandem Micro-reactor GC/MS.

When a GC/MS system is coupled with a pressurized reactor, the separation efficiency and the retention time are directly affected by the reactor pressure. To keep the GC column flow rate constant irrespective of the reaction pressure, a restrictor capillary tube and an open split interface are attached between the GC injection port and the head of a GC separation column. The capability of the attached modules is demonstrated for the on-line GC/MS analysis of catalytic reaction products of a bio-oil model sample (guaiacol), produced under a pressure of 1 to 3 MPa.

TiO2 Feather Duster as Effective Polysulfides Restrictor for Enhanced Electrochemical Kinetics in Lithium-Sulfur Batteries.

The rechargeable lithium-sulfur battery is recognized as a promising candidate for electrochemical energy storage system because of their exceptional advance in energy density. However, the fast capacity decay of sulfur cathode caused by polysulfide dissolution and low specific capacity caused by poor electrical conductivity still impede the further development of lithium-sulfur battery. To address above issues, this study reports the synthesis of feather duster-like TiO2 architecture by in situ growth of TiO2 nanowires on carbon cloth and further evaluates as sulfur host material. The strong chemical binding interaction between the polysulfides and TiO2 feather duster efficiently restrains the shuttle effect, leading to enhanced electrochemical kinetics. Besides, the in situ grown TiO2 NWs array also supply high surface for sulfur-loading and fast path for electron transfer and ion diffusion. As results, the novel CC/TiO2 /S composite cathode exhibits a high capacity of 608 mA h g-1 at 1.0 C after 700 cycles corresponding to capacity decay as low as 0.045% per cycle with excellent Coulombic efficiency higher than 99.5%.