Microtubule specialization by +TIP networks: from mechanisms to functional implications.

To fulfill their actual cellular role, individual microtubules become functionally specialized through a broad range of mechanisms. The 'search and capture' model posits that microtubule dynamics and functions are specified by cellular targets that they capture (i.e., a posteriori), independently of the microtubule-organizing center (MTOC) they emerge from. However, work in budding yeast indicates that MTOCs may impart a functional identity to the microtubules they nucleate, a priori. Key effectors in this process are microtubule plus-end tracking proteins (+TIPs), which track microtubule tips to regulate their dynamics and facilitate their targeted interactions. In this review, we discuss potential mechanisms of a priori microtubule specialization, focusing on recent findings indicating that +TIP networks may undergo liquid biomolecular condensation in different cell types.

Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis.

BACKGROUND & AIMS: Overt hepatic encephalopathy (OHE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) placement, given its high incidence and possibility of refractoriness to medical treatment. Nevertheless, the impact of post-TIPS OHE on mortality has not been investigated in a large population. METHODS: We designed a multicenter, non-inferiority, observational study to evaluate the mortality rate at 30 months in patients with and without OHE after TIPS. We analyzed a database of 614 patients who underwent TIPS in three Italian centers and estimated the cumulative incidence of OHE and mortality with competitive risk analyses, setting the non-inferiority limit at 0.12. RESULTS: During a median follow-up of 30 months (IQR 12-30), 293 patients developed at least one episode of OHE. Twenty-seven (9.2%) of them experienced recurrent/persistent OHE. Patients with OHE were older (64 [57-71] vs. 59 [50-67] years, p <0.001), had lower albumin (3.1 [2.8-3.5] vs. 3.25 [2.9-3.6] g/dl, p = 0.023), and had a higher prevalence of pre-TIPS OHE (15.4% vs. 9.0%, p = 0.023). Child-Pugh and MELD scores were similar. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03 (95% CI -0.042 to 0.102). Multivariable analysis showed that age (subdistribution hazard ratio 1.04, 95% CI 1.02-1.05, p <0.001) and MELD score (subdistribution hazard ratio 1.09, 95% CI 1.05-1.13, p <0.001), but not post-TIPS OHE, were associated with a higher mortality rate. Similar results were obtained when patients undergoing TIPS for variceal re-bleeding prophylaxis (n = 356) or refractory ascites (n = 258) were analyzed separately. The proportion of patients with persistent OHE after TIPS was significantly higher in the group of patients who died. The robustness of these results was increased following propensity score matching. CONCLUSION: Episodic OHE after TIPS is not associated with mortality in patients undergoing TIPS, regardless of the indication. IMPACT AND IMPLICATIONS: Overt hepatic encephalopathy (OHE) is a common complication in patients with advanced liver disease and it is particularly frequent following transjugular intrahepatic portosystemic shunt (TIPS) placement. In patients with cirrhosis outside the setting of TIPS, the development of OHE negatively impacts survival, regardless of the severity of cirrhosis or the presence of acute-on-chronic liver failure. In this multicenter, non-inferiority, observational study we demonstrated that post-TIPS OHE does not increase the risk of mortality in patients undergoing TIPS, irrespective of the indication. This finding alleviates concerns regarding the weight of this complication after TIPS. Intensive research to improve patient selection and risk stratification remains crucial to enhance the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival.

BnaC4.BOR2 mediates boron uptake and translocation in Brassica napus under boron deficiency.

Boron (B) is an essential microelement in plant growth and development. However, the molecular mechanisms underlying B uptake and translocation in Brassica napus are poorly understood. Herein, we identified a low-B (LB)-inducible gene, namely BnaC4.BOR2, with high transcriptional activity in root tips, stele cells, leaves, and floral organs. The green fluorescence protein labelled BnaC4.BOR2 protein was localised to the plasma membrane to demonstrate the B efflux activity in yeast and Arabidopsis. BnaC4.BOR2 knockout considerably reduced B concentration in the root and xylem sap, and altered B distribution in different organs at low B supply, exacerbating B sensitivity at the vegetative and reproductive stages. Additionally, the grafting experiment showed that BnaC4.BOR2 expression in the roots contributed more to B deficiency adaptability than that in the shoots. The pot experiments with LB-soil revealed B concentration in leaves and siliques of BnaC4.BOR2 mutants were markedly reduced, showing an obvious B-deficient phenotype of 'flowering without seed setting' and a considerable reduction in seed yield in B-deficient soil. Altogether, the findings of this study highlight the crucial role of BnaC4.BOR2 in B uptake and translocation during B. napus growth and seed yield under LB conditions.

French guidelines on TIPS: Indications and modalities.

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension-related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre-therapeutic assessment, in the procedure itself and in the follow-up have led the board of the French Association for the Study of the Liver to establish recommendations.

An unusual case of endotipsitis: persistent infection and migration to the right atrium of a transjugular intrahepatic portosystemic shunt (TIPS).

Endotipsitis is an underdiagnosed entity mainly because it requires a high initial level of suspicion. It should be considered in the differential diagnosis of persistent bacteremia in the cirrhotic patient with TIPS. Most cases are treated conservatively with a long-term antibiotherapy, due to the impossibility of surgical removal of the TIPS, except in a liver transplant or autopsy. The patient we present had endotipsitis that manifested as persistent bacteremia with thrombosis of the TIPS. Initially, conservative management with intravenous antibiotherapy was performed; however, due to mechanical complications caused by migration of the original endoprosthesis, it was decided to perform surgery.

The Long-Term Impact of the Tips From Former Smokers® Campaign on Calls to 1-800-QUIT-NOW, 2012-2023.

INTRODUCTION: There is substantial evidence that mass media campaigns increase calls to quitlines and smoking cessation. In 2012, the Centers for Disease Control and Prevention launched the first federally funded national tobacco education campaign, Tips From Former Smokers® (i.e. Tips), which has since aired television advertisements annually. To date, no studies have examined the long-term effect of a national smoking cessation campaign on quitline calls. This study examined the long-term impact of Tips television ads on calls to 1-800-QUIT-NOW from 2012 through 2023. METHODS: Exposure to the Tips campaign was measured using weekly television gross rating points (GRPs) in each U.S. designated market area. We obtained data on calls to 1-800-QUIT-NOW from the National Cancer Institute and used linear regression to model calls to 1-800-QUIT-NOW, from 2012 through 2023, as a function of weekly media market-level GRPs for Tips television ads. Using the regression model results, we calculated predicted values of calls to 1-800-QUIT-NOW across observed GRP values to determine the total additional calls to 1-800-QUIT-NOW that were attributable to the Tips campaign during 2012-2023. RESULTS: Tips GRPs were positively and significantly associated with calls to 1-800-QUIT-NOW across all years (b = 39.94, p < 0.001). Based on this association, we estimate the Tips campaign generated nearly 2.1 million additional calls to 1-800-QUIT-NOW during 2012-2023. CONCLUSIONS: Exposure to the Tips campaign has consistently and significantly increased calls to tobacco quitlines. IMPLICATIONS: Quitlines provide evidence-based support to help people quit smoking. They have been shown to increase the likelihood of successfully quitting. Mass media campaigns have promoted quitline services, and quitline calls have increased significantly with media promotion. The long-term effect of campaigns - like the Centers for Disease Control and Prevention's Tips From Former Smokers® (i.e. Tips) - on quitline calls has not been determined. From 2012 through 2023, exposure to the Tips campaign is estimated to have generated nearly 2.1 million additional calls to 1-800-QUIT-NOW. This study supports continued use of mass media to promote quitlines.

The bacterial displacement test: an in vitro microbiological test for the evaluation of intermittent catheters and urinary tract infection.

AIMS: Intermittent catheters (ICs) are commonly used in bladder management, but catheter-associated urinary tract infections (CAUTIs) remain challenging. Insertion tips may reduce the risk of CAUTIs by minimizing bacterial transfer along the urinary tract. However, there are few laboratory tests to evaluate such technologies. We describe the use of an adapted in vitro urethra agar model to assess bacterial displacement by ICs. METHODS AND RESULTS: Simulated urethra agar channels (UACs) were prepared with catheter-specific sized channels in selective media specific to the challenge organisms. UACs were inoculated with Escherichia coli and Enterococcus faecalis before insertion of ICs, and enumeration of UAC sections was performed following insertion. Four ICs were evaluated: Cure Catheter® Closed System (CCS), VaPro Plus Pocket™, Bard® Touchless® Plus, and SpeediCath® Flex Set. CCS demonstrated significantly reduced bacterial displacement along the UACs compared to the other ICs and was also the only IC with undetectable levels of bacteria toward the end of the UAC (representing the proximal urethra). CONCLUSION: The bacterial displacement test demonstrated significant differences in bacterial transfer between the test ICs with insertion tips, which may reflect their different designs. This method is useful for evaluating CAUTI prevention technology and may help guide future technology innovations.

Predictors and Outcomes of Post-transjugular Intrahepatic Portosystemic Shunt Liver Failure in Patients with Cirrhosis.

BACKGROUND: Post-transjugular intrahepatic portosystemic shunt (TIPS) liver failure (PTLF) is a serious complication of TIPS procedure with poor patient prognosis. This study tried to investigate the incidence of PTLF following elective TIPS procedure and evaluated possible predictive factors for the same. METHODS: A retrospective analysis of patients who underwent elective TIPS placement between 2012 and 2022 and was conducted to determine development of PTLF (≥ 3-fold bilirubin and/or ≥ 2-fold INR elevation from the baseline) within 30 days following TIPS procedure. Medical record review was done and factors predicting development of PTLF and the 90-day transplant-free survival was determined. RESULTS: Thirty of 352 (8.5%) patients developed PTLF within 30 days of TIPS (mean age 54.2 ± 9.8 years, 83% male). The etiology of cirrhosis was related to non-alcoholic steatohepatitis (NASH) in 50%, alcohol in 33.3%, and hepatitis B/C virus infection in 16.7% of the patients. The mean Child-Turcotte-Pugh (CTP) score was 9.5 ± 1.2 and mean model for end stage liver disease (MELD) score was 14.6 ± 4.5 at the time of admission in patients who developed PTLF. The indication for TIPS was recurrent variceal bleed in 50% (15 of 30) and refractory ascites in 46.7% (14 of 30) patients with PTLF. Multivariate analysis identified prior HE (OR 6.1; CI 2.57-14.5, p < 0.0001) and higher baseline CTP score (OR 1.47; CI 1.07-2.04; p = 0.018) as predictors of PTLF. PTLF was associated with significantly lower 90-day transplant-free survival, as compared to patients without PTLF (40% versus 96%, p < 0.001). CONCLUSION: Almost 10% of patients with cirrhosis develop post-TIPS liver failure and is associated with significant early mortality and morbidity. Higher baseline CTP score and prior HE were identified as predictors for PTLF.

A droplet vitrification cryopreservation protocol for conservation of hops (Humulus lupulus) genetic resources.

Hops (Humulus lupulus L.) is essentially used in the brewing industry as it contributes to flavor, and aroma of beer. However, the genetic diversity of hops is increasingly threatened by diseases, environmental changes, and urbanization. Cryopreservation has emerged as a pivotal strategy for safeguarding and maintaining the genetic diversity of hops. The present work presents a comprehensive study on the cryopreservation of hops, focusing on the development and optimization of a droplet vitrification based cryopreservation protocol. Shoot tips excised from one month old in vitro cultures were precultured on 0.3 M sucrose, dehydrated in a loading solution followed by treatment with PVS2 solution for different durations. Significant effect of PVS2 dehydration was observed on post-thaw survival and regeneration after cryoconservation with maximum 50% post-thaw regeneration observed in shoot tips dehydrated in PVS2 for 30 min. Genetic fidelity of the regenerated plants was confirmed using 30 ISSR markers. Reproducibility of the developed protocol was tested on seven other accessions and post thaw regeneration ranging from 43 to 70% was observed across the accessions. The present study reports a highly efficient protocol for conservation of hops germplasm. The results indicate that droplet vitrification can be used as a reliable and sustainable approach for hop genetic preservation, with high survival rates and minimal genetic alterations observed in cryopreserved samples. To the best of our knowledge, this is the first report on DV based cryopreservation of hops germplasm.

Leaks after laparoscopic sleeve gastrectomy: 2024 update on risk factors.

PURPOSE: Leaks after sleeve gastrectomy remain a deadly complication significantly affecting outcomes and medical costs. The aim of the present review is to provide an updated decalogue on leak prevention. METHODS: Risk factors of leakage after LSG were examined based on an extensive review of literature (in period time 2016-2024) and summary of evidence was provided using Oxford levels of evidence scale. RESULTS: Pathogenesis of leakage after LSG still remain related to ischemic and mechanical factors and, therefore, no new evidence has been reported. Conversely, some technical aspect of the procedure has changed: bougie size, antrum resection, staple line reinforcement, and intraoperative leak testing. CONCLUSIONS: Bougie size 36 F is effective and safe achieving similar leakage rate compared to larger bougie sizes (EL:2) 2024 UPDATE; There is no significant difference in the leak rate between restrictive (< 6 cm) and conservative (6 cm) antrum resection (EL: 1) 2024 UPDATE; Surgical experience and case volume affect the leak rate more consistently than every kind of SLR (EL: 2) 2024 UPDATE; Intraoperative leak test after LSG represents a decision based on surgeon preference in absence of standardization (endoscopy, bubble test, methylene blue, indocyanine green.) and strong detection/prevention rate (EL: 3) 2024 UPDATE.

A rare case of severe tricuspid regurgitation caused by TIPS stent migrating into the right atrium.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a common, effective and reliable treatment modality for portal hypertension. Migration of the TIPS stent into the right atrium is a rare and fatal complication. CASE PRESENTATION: We report a case of severe tricuspid regurgitation caused by a stent migrating into the right atrium in a patient hospitalized with refractory ascites due to cirrhosis. DISCUSSION: In this case, it is noteworthy that secondary stenting, which is necessary especially in cases of occlusion, significantly increases the risk of migration. CONCLUSION: Although a rare complication, intracardiac stent migration should be considered in patients with a history of TIPS in the presence of a new heart murmur and signs of arrhythmia.

Tips and tricks for a correct interpretation of contrast-enhanced ultrasound.

Although contrast-enhanced ultrasound (CEUS) is a widespread and easily manageable technique, image interpretation errors can occur due to the operator's inexperience and/or lack of knowledge of the frequent pitfalls, which may cause uncertain diagnosis and misdiagnosis. Indeed, knowledge of the basic physical and technical principles of ultrasound is needed both to understand sonographic image findings and to evaluate the potential and limits of the method. Like the B-mode ultrasound, the quality of the CEUS examination is also subject not only to the adequate manual skill of the operator but also to his/her deep knowledge of the technique which improves the quality of the image helping avoid misleading artifacts. In this review, the main parameters influencing a CEUS examination will be described by taking into account the most common errors and pitfalls and their possible solutions.

Genetic Analysis and Fine Mapping of a New Rice Mutant, Leaf Tip Senescence 2.

Premature leaf senescence significantly reduces rice yields. Despite identifying numerous factors influencing these processes, the intricate genetic regulatory networks governing leaf senescence demand further exploration. We report the characterization of a stably inherited, ethyl methanesulfonate(EMS)-induced rice mutant with wilted leaf tips from seedling till harvesting, designated lts2. This mutant exhibits dwarfism and early senescence at the leaf tips and margins from the seedling stage when compared to the wild type. Furthermore, lts2 displays a substantial decline in both photosynthetic activity and chlorophyll content. Transmission electron microscopy revealed the presence of numerous osmiophilic granules in chloroplast cells near the senescent leaf tips, indicative of advanced cellular senescence. There was also a significant accumulation of H2O2, alongside the up-regulation of senescence-associated genes within the leaf tissues. Genetic mapping situated lts2 between SSR markers Q1 and L12, covering a physical distance of approximately 212 kb in chr.1. No similar genes controlling a premature senescence leaf phenotype have been identified in the region, and subsequent DNA and bulk segregant analysis (BSA) sequencing analyses only identified a single nucleotide substitution (C-T) in the exon of LOC_Os01g35860. These findings position the lts2 mutant as a valuable genetic model for elucidating chlorophyll metabolism and for further functional analysis of the gene in rice.

Endoscopic Colorectal Stenting: Lessons Learned from a Two-Decade Journey.

Endoscopic colorectal stenting has gained momentum over the last two decades as a viable alternative to surgical intervention in a subgroup of patients with colorectal disease. Stenting can be used as a temporizing bridge to surgical intervention or as a definitive treatment measure. Patient selection and the technical expertise of the endoscopist are of paramount importance to optimize the clinical outcome. Technical skills in therapeutic endoscopy and the choice of proper equipment including the consumables are required for the conduct of a safe and successful procedure. In this article, we share the lessons learned from a two-decade journey of the senior author with therapeutic endoscopy.

Soluble urokinase plasminogen activator receptor levels predict survival in patients with portal hypertension undergoing TIPS.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion. Methods: suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses. Results: suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis. Conclusion: suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion. Impact and implications: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not.

Colonic Varices as an Unsettling Cause of Lower Gastrointestinal Bleeding.

Colonic varicose veins are very rare and are usually discovered incidentally during colonoscopy or when complications occur, such as lower gastrointestinal (GI) bleeding. The primary cause of colonic varices is usually portal hypertension secondary to liver disease or very rarely due to pancreatic disease (e.g., pancreatic adenocarcinoma). Varicose veins secondary to cirrhosis are often seen in the upper GI tract but rarely in the lower GI tract. Here, we report a 54-year-old woman who presented with colonic varices due to decompensated alcoholic cirrhosis. The main intention of this case report was to raise awareness of the possibility of developing colonic varices from liver cirrhosis and to promptly identify and manage its side effects due to the major complication which is lower GI bleeding.

Use of the gun-sight technique to create a parallel transjugular intrahepatic portosystemic shunt.

A parallel shunt (PS) is often necessary to regain portal decompression in a dysfunctional transjugular intrahepatic portosystemic shunt (TIPS). Here, we successfully utilized the gun-sight technique to create a PS. An 81-year-old male with decompensated NASH cirrhosis and recent TIPS placement presents with recurrent ascites and pleural effusions in the setting of a persistent portosystemic gradient. Due to a lack of access to endovascular ultrasound and complex patient anatomy, a gun-site technique was approached to create a PS (left portal vein [PV] to left hepatic vein [HV]). After the right HV and existing TIPS were accessed via the right internal jugular vein access, the left HV was accessed. Following a left portal venogram, 10 mm snares were placed into the left HV and the left PV. An 18-gauge needle was then fluoroscopically placed through and through both snares. A 0.035 Glidewire was snared with the help of both snares, establishing access from the left HV via the left PV to the right PV. After serial dilation, a roadrunner wire and catheter were placed into the main PV and superior mesenteric vein, followed by stent dilation. Post-TIPS portal venogram showed prompt flow of contrast from the main PV to the right atrium without any stenosis through both TIPS stents in the left and right PVs. Initial and postprocedural TIPS gradients were 24 mm Hg and 6 mm Hg, respectively. Gun-site technique is a valuable technique in creating a parallel TIPS shunt.

Interventional Radiology Management of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a clinically severe and devastating complication of decompensated liver disease affecting mortality, quality of life for patients and families, hospital admission rates, and overall health-care costs globally. Depending on the cause of HE, several medical treatment options have been developed and become available. In some refractory HE, such as spontaneous portosystemic shunt-related HE (SPSS-HE) or posttransjugular intrahepatic portosystemic shunt HE (post-TIPS HE), advanced interventional radiology (IR) procedures have been used, and shown to be effective in these conditions. This review presents 2 effective IR procedures for managing SPSS-HE and post-TIPS HE.

Transjugular Intrahepatic Portosystemic Shunt (TIPS) Extension for Transhepatic Mesocaval Shunt Creation: A Case Series for Treating Refractory Upper Gastrointestinal Bleeding in Patients with Chronic Portal Vein Thrombosis.

Transjugular intrahepatic portosystemic shunt (TIPS) is known to benefit patients with decompensated liver disease by alleviating portal pressure. However, TIPS creation is technically difficult and challenging to perform in patients with chronic portal vein thrombosis (PVT) (4,5). Multiple endovascular techniques for portal vein recanalization with or without creating portosystemic shunt are available to decompress and alleviate portal hypertension in patients with PVT. In this case series, we represent TIPS extension to create an endovascular mesocaval shunt for the treatment of refractory upper gastrointestinal bleeding.

Giant thigh lipomas: from a case report to a guide for the surgical approach.

The issue of international migration and health has received increased attention since its rise due to empirical studies on the immigrant paradox. Less examined has been research focused on countries in the Global South with growing immigrant population share and contentious debates on implications. Using data from the longitudinal National Income Dynamics Study (NIDS) (2008-2017) and panel logistic regression this study focused on evaluating whether reported physical health, mental health, and life satisfaction are all associated with immigrant status in South Africa. Accounting for several sociodemographic factors, results emanating from analysis showed no significant evidence of association between overall immigration status and self-reported health or life satisfaction. This however did not apply to depression as immigrants were found to be significantly less likely to report depressive level scores. Interestingly, preference to migrate was also found to be significantly associated with depression, and life satisfaction. Further evaluation amongst racial groups showed that African immigrants are also significantly more likely to report better health than non-immigrant counterparts. This study argues for the need of contextualisation of the immigrant paradox as evidence thereof varies dependent on specific outcomes and communities. The importance of other associated social determinants of wellbeing is also highlighted since gender, race, age, class, education, relationship status, location, and behavioural factors were found to be significantly associated with wellbeing. Policies should thus be aimed at reducing structural inequalities in broad whilst also introducing social programmes that reduce behavioural or lifestyle activities that have negative implications on wellbeing.