Treatment of portal vein thrombosis in cirrhosis is associated with no survival advantage: a retrospective controlled study.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is associated with increased mortality post-transplant, but treatment of the clot is not definitively associated with improvement in mortality. We aimed to assess the effect of anticoagulation (AC), transjugular intrahepatic portosystemic shunt (TIPS), or best supportive care only (SCO) as treatment options in patients with PVT and cirrhosis. METHODS: This was a retrospective controlled cohort study from a large urban health system. Patients with cirrhosis and PVT were identified and analyzed based on treatment provided (1) AC, (2) TIPS, and (3) SCO. Outcomes included patent portal vein at the end of follow-up and overall mortality. RESULTS: 150 patients on AC, 93 who underwent TIPS, and 172 who received SCO were analyzed. Final portal vein (PV) patency was not significantly different by treatment group in those with partial obstruction at presentation (p = 0.64), while any treatment improved final patency over SCO in those presenting with complete obstruction (p = 0.01). Rate of survival, transplant-free survival, and successful liver transplantation were not different between treatment groups. CONCLUSION: In our cohorts, treatment of PVT versus SCO showed no impact on survival in those presenting with partial obstruction of the PV. In those with complete obstruction, any treatment was more effective than SCO in achieving patency of the PV, but overall survival was no different. PVT may not be a pathologic mechanism that causes worsening of liver disease but may be an event in the progression that in itself is not directly responsible for worsening liver function.

Structural analysis of microtubule binding by minus-end targeting protein Spiral2.

Microtubules (MTs) are dynamic cytoskeletal polymers that play a critical role in determining cell polarity and shape. In plant cells, acentrosomal MTs are localized on the cell surface and are referred to as cortical MTs. Cortical MTs nucleate in the cell cortex and detach from nucleation sites. The released MT filaments perform treadmilling, with the plus-ends of MTs polymerizing and the minus-ends depolymerizing. Minus-end targeting proteins, -TIPs, include Spiral2, which regulates the minus-end dynamics of acentrosomal MTs. Spiral2 accumulates autonomously at MT minus-ends and inhibits filament shrinkage, but the mechanism by which Spiral2 specifically recognizes minus-ends of MTs remains unknown. Here we describe the crystal structure of Spiral2's N-terminal MT-binding domain. The structural properties of this domain resemble those of the HEAT repeat structure of the tumor overexpressed gene (TOG) domain, but the number of HEAT repeats is different and the conformation is highly arched. Gel filtration and co-sedimentation analyses demonstrate that the domain binds preferentially to MT filaments rather than the tubulin dimer, and that the tubulin-binding mode of Spiral2 via the basic surface is similar to that of the TOG domain. We constructed an in silico model of the Spiral2-tubulin complex to identify residues that potentially recognize tubulin. Mutational analysis revealed that the key residues inferred in the model are involved in microtubule recognition, and provide insight into the mechanism by which end-targeting proteins stabilize MT ends.

Proximal splenic artery embolization for treatment of refractory ascites, a single-center experience.

AIM: Refractory ascites from portal hypertension can be managed with regular large-volume paracentesis (LVP) or transjugular intrahepatic portosystemic shunt (TIPS). Large-volume paracentesis is clinically unsatisfactory and many patients are ineligible or relatively contraindicated for TIPS or Denver shunt. Proximal splenic artery embolization (PSAE) using coils or plugs reduces but does not completely stop splenic arterial inflow, differing from distal splenic artery embolization techniques. By reducing splenic arterial inflow, splenic vein outflow is also decreased, lowering portal pressure and thus treating refractory ascites. METHODS: In this institutional review board-approved single-center retrospective study, electronic medical records were reviewed to obtain demographics and baseline clinical and laboratory data, paracentesis data before and after PSAE, PSAE procedural details, and follow-up imaging up to 12 months post-PSAE. Mixed-effects models were used for statistical analysis. RESULTS: Ten patients with LVP-dependent ascites meeting inclusion criteria underwent PSAE for refractory ascites from 2017 to 2024. Prior to PSAE, four patients had TIPS, three had liver transplants, and the remaining three were neither TIPS nor transplant candidates. In the month before PSAE, patients averaged 3.8 ± 1.7 paracentesis sessions, draining a total of 20.84 ± 10.39 L of fluid monthly. Post-PSAE, the number of paracentesis sessions decreased to 2.1 ± 2.7, 1.0 ± 1.7, 0.4 ± 1.1, and 0.0 ± 0.0 at 1, 3, 6, and 12 months, respectively (p = 0.03). Corresponding ascitic volume drained decreased to 8.7 ± 10.3, 2.7 ± 6.4, 2.0 ± 5.4, and 0.0 ± 0.0 L (p = 0.01). Over the 12-month follow-up period, 6 of 10 patients became LVP-independent. CONCLUSION: Proximal splenic artery embolization can improve refractory ascites in certain patients with portal hypertension, thus providing safe and effective treatment as an alternative to TIPS.

Ten quick tips for clinical electroencephalographic (EEG) data acquisition and signal processing.

Electroencephalography (EEG) is a medical engineering technique aimed at recording the electric activity of the human brain. Brain signals derived from an EEG device can be processed and analyzed through computers by using digital signal processing, computational statistics, and machine learning techniques, that can lead to scientifically-relevant results and outcomes about how the brain works. In the last decades, the spread of EEG devices and the higher availability of EEG data, of computational resources, and of software packages for electroencephalography analysis has made EEG signal processing easier and faster to perform for any researcher worldwide. This increased ease to carry out computational analyses of EEG data, however, has made it easier to make mistakes, as well. And these mistakes, if unnoticed or treated wrongly, can in turn lead to wrong results or misleading outcomes, with worrisome consequences for patients and for the advancements of the knowledge about human brain. To tackle this problem, we present here our ten quick tips to perform electroencephalography signal processing analyses avoiding common mistakes: a short list of guidelines designed for beginners on what to do, how to do it, and what not to do when analyzing EEG data with a computer. We believe that following our quick recommendations can lead to better, more reliable and more robust results and outcome in clinical neuroscientific research.

Ten quick tips for electrocardiogram (ECG) signal processing.

The electrocardiogram (ECG) is a powerful tool to measure the electrical activity of the heart, and the analysis of its data can be useful to assess the patient's health. In particular, the computational analysis of electrocardiogram data, also called ECG signal processing, can reveal specific patterns or heart cycle trends which otherwise would be unnoticeable by medical experts. When performing ECG signal processing, however, it is easy to make mistakes and generate inflated, overoptimistic, or misleading results, which can lead to wrong diagnoses or prognoses and, in turn, could even contribute to bad medical decisions, damaging the health of the patient. Therefore, to avoid common mistakes and bad practices, we present here ten easy guidelines to follow when analyzing electrocardiogram data computationally. Our ten recommendations, written in a simple way, can be useful to anyone performing a computational study based on ECG data and eventually lead to better, more robust medical results.

Exogenous Cytokinin Induces Callus and Protocorm-Like-Bodies Formation in In Vitro Root Tips of Vanilla planifolia Andrews.

Vanilla is a popular flavouring essence derived from the pods of vanilla orchid plants. Due to the high demand for vanilla flavour, high yielding vanilla plantlets are necessary for establishing vanilla plantations. Clonal micropropagation is a viable technique for the mass production of high yielding vanilla plantlets. This study reports an efficient regeneration protocol by using cytokinin as the sole plant growth regulator to regenerate plantlets from the root tips of a commercial vanilla orchid species, Vanilla planifolia. Most studies to date have reported using seeds and nodes as starting explants for in vitro micropropagation of vanilla orchids. So far, regeneration from roots has not been very successful. Previous studies favoured the use of auxins only or high auxin to cytokinin ratios to induce callus, and sole cytokinins were used for direct shoot regeneration. However, it was sporadically observed in plantlets regeneration of V. planifolia that multiple shoots were regenerated from the tips of intact aerial roots submerged in media. This study therefore investigated the regeneration of excised vanilla root tips through the application of most commonly used auxins (1-naphthaleneacetic acid and 2,4-dichlorophenoxyacetic acid) and cytokinins (6-benzylaminopurine and thidiazuron). High auxin presence is known to promote callusing in in vitro plants. However, in this study, auxin treatment inhibits callusing in root tips. While cytokinin treatments, even at low levels, has promoted high rate of callusing. These callus cells regenerate into protocorm-like-body (PLB) shoots when cytokinin levels are increased to 0.5 mg/mL 6-benzylaminopurine (BAP) under light conditions. The findings of the study have the potential of providing large quantity of high yielding vanilla plantlets through clonal micropropagation.

Transjugular intrahepatic portosystemic shunt combined with dual-access thrombolysis for acute severe non-cirrhotic portal-mesenteric vein thrombosis.

OBJECTIVE: Non-cirrhotic porto-mesenteric vein thrombosis (NC-PMVT) is a rare but severe clinical condition. The study aims to assess the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) coupled with dual-access thrombolysis in patients with acute severe NC-PMVT. METHODS: From January 2018 to February 2023, a total of 25 patients with acute severe NC-PMVT who were treated with TIPS in conjunction with mechanical thrombectomy and dual-access thrombolysis. The period of thrombolysis was determined by the improvement of clinical symptoms and vascular recanalization. The technical success, recanalization rate, clinical success, and procedure-related complications were analyzed. RESULTS: The technical success rate was 100 %. The median duration for thrombolytic catheter removal was 5 (IQR 3.5 - 7) days. Full and partial recanalization were accomplished in 10 (40 %) and 15 (60 %) patients respectively before discharge. No significant procedure-related complications were reported. The clinical success rate was 88 %, with a mortality rate of 12 %. Over a median follow-up of 8 months, 3/22 (13.64 %) patients had a recurrence of thrombosis; 1/22 (4.54 %) patients underwent partial intestinal resection one and a half months post-discharge; the remaining patients did not experience any portal hypertensive complications. CONCLUSION: The combination of TIPS and dual-access thrombolysis appears to be safe and effective for patients with acute severe NC-PMVT.

Refractory massive chylothorax following robot-assisted laparoscopic splenectomy with pericardial devascularization treated with trans-jugular intrahepatic portosystemic shunt: a case report.

The development of a chylothorax after robot-assisted laparoscopic splenectomy combined with pericardial devascularization (LSPD) is rare. The robot-assisted procedure is similar to the standard LSPD, but surgeons must remain vigilant about potential chylothorax caused by recurrence of portal hypertension in patients with cirrhosis, an event that leads to variceal bleeding in the gastric fundus or a massive chylothorax caused by a thoracic duct fistula. We report a rare case of massive chylothorax after robot-assisted LSPD and review the literature to help elucidate the mechanisms of portal hypertension after LSPD, reduce surgical complications, and improve long-term patient outcomes. After LSPD, portal pressure monitoring, coagulation function testing, and portal vein CT imaging help in excluding portal vein thromboses and ensuring appropriate anticoagulation to reduce the development of thoracic duct fistulas. If portal hypertension recurs after surgery and a high-output chylothorax develops, conservative treatment becomes ineffective. Treatment with an active trans-jugular intrahepatic portosystemic shunt (TIPS) is recommended to lower the portal pressure.

AtML: An Arabidopsis thaliana root cell identity recognition tool for medicinal ingredient accumulation.

Arabidopsis thaliana synthesizes various medicinal compounds, and serves as a model plant for medicinal plant research. Single-cell transcriptomics technologies are essential for understanding the developmental trajectory of plant roots, facilitating the analysis of synthesis and accumulation patterns of medicinal compounds in different cell subpopulations. Although methods for interpreting single-cell transcriptomics data are rapidly advancing in Arabidopsis, challenges remain in precisely annotating cell identity due to the lack of marker genes for certain cell types. In this work, we trained a machine learning system, AtML, using sequencing datasets from six cell subpopulations, comprising a total of 6000 cells, to predict Arabidopsis root cell stages and identify biomarkers through complete model interpretability. Performance testing using an external dataset revealed that AtML achieved 96.50% accuracy and 96.51% recall. Through the interpretability provided by AtML, our model identified 160 important marker genes, contributing to the understanding of cell type annotations. In conclusion, we trained AtML to efficiently identify Arabidopsis root cell stages, providing a new tool for elucidating the mechanisms of medicinal compound accumulation in Arabidopsis roots.

The Toulouse algorithm identifies patients with increased risk of cardiac decompensation only in patients with TIPS for refractory ascites.

INTRODUCTION AND OBJECTIVES: TIPS placement is an effective, possibly life-saving, treatment for complications of portal hypertension. The pressure shift induced by the stent can lead to cardiac decompensation (CD). We investigated the incidence of CD, possible variables associated with CD and the validity of the Toulouse algorithm for risk prediction of CD post-TIPS. PATIENTS AND METHODS: A total of 106 patients receiving TIPS for variceal bleeding (VB, 41.5%) or refractory ascites (RA, 58.5%) with available echocardiography and NT-proBNP results were included and retrospectively reviewed. Development of CD between time of TIPS placement and occurrence of liver transplantation, death or loss-to-follow-up was recorded. Competing risk regression analysis was performed to assess which baseline variables predicted occurrence of CD post-TIPS. RESULTS: A total of 12 patients (11.3%) developed CD after a median of 11.5 days (IQR 4 to 56.5) post-TIPS. Multivariate regression showed age (HR 1.06, p = 0.019), albumin (HR 1.10, p = 0.009) and NT-proBNP (HR 1.00, p = 0.023) at baseline predicted CD in the RA group. No clear predictors were found in those receiving TIPS for VB. Correspondingly, the Toulouse algorithm successfully identified patients at risk for CD, however only in the RA population (zero risk 0% vs. low risk 12.5% vs. high risk 35.3% with CD; p = 0.003). CONCLUSIONS: CD is not an infrequent complication post-TIPS occurring in 1/10 patients. The Toulouse algorithm can identify patients at risk of CD, though only in patients receiving TIPS for RA. Allocation to the high-risk category warrants close monitoring but should not preclude TIPS placement.

Excision of arteriovenous malformation in an emergency situation - A case report.

An arteriovenous malformation (AVM) is an infrequent congenital vascular anomaly that can affect the vasculature and involve the endothelium and neighboring cells of any anatomical structure. AVMs are characterized histologically by abnormal AV shunts with atypical interconnecting capillary beds. AVM can cause functional and esthetic issues like face asymmetry, pain, osteolytic changes, and unanticipated hemorrhage or squeeze and tear of the surrounding tissue without causing any symptoms. The literature search yielded limited case reports on AVMs in the facial region. Insufficient diagnosis, limited knowledge, and a lack of literature can lead to severe bleeding and potentially fatal hemorrhagic incidents following dental procedures like tooth extraction, surgery, puncture wounds, or blunt injuries in the affected area. In this manuscript, we report a case of AV malformation involving the left cheek and buccal mucosa region in a 37-year-old male patient who reported uncontrolled bleeding after trauma. This report highlights the management of AV malformation in an emergency by facial artery ligation and surgical excision.

Transjugular antegrade transvenous obliteration, with and without portal decompression, for management of rectal variceal hemorrhage.

PURPOSE: To report antegrade transvenous obliteration, with or without concurrent portosystemic shunt creation, for the treatment of hemorrhagic rectal varices. MATERIALS AND METHODS: Eight patients, including five (62.5%) females and three (37.5%) males, with mean age of 55.8 ± 13.8 years (range: 30-70 years), underwent transjugular-approach antegrade transvenous obliteration of rectal varices, with or without portosystemic shunt creation. Demographic data, procedural details, technical success of variceal obliteration, clinical success, adverse events, and follow-up outcomes were retrospectively recorded. Clinical success was defined as resolution of rectal hemorrhage. RESULTS: Portal venous access was achieved via a transjugular intrahepatic approach in all patients. The inferior mesenteric vein was selected, and foamy sclerosant (1:2:3 mixture by volume of ethiodized oil: sodium tetradecyl sulfate: air) was injected into the rectal varices with antegrade balloon occlusion in seven (87.5%) and without balloon occlusion in one (12.5%). Five of eight (62.5%) patients underwent concomitant transjugular intrahepatic portosystemic shunt (TIPS) creation (mean diameter 8.4 ± 0.9-mm) immediately following transvenous obliteration. Technical success of variceal obliteration was achieved in all patients. There were no immediate post-procedural adverse events. There were no reported occurrences of rectal ischemia, perforation, or stricture following obliteration. Two (40%) of the patients who underwent concomitant TIPS creation developed hepatic encephalopathy within 30 days of the procedure, which was medically managed. Clinical resolution of hemorrhage was achieved in all patients with no recurrent rectal variceal hemorrhage during mean follow-up of 666 ± 396 days (range: 14 - 1,224 days). CONCLUSION: Transvenous obliteration, with or without concurrent TIPS creation, is feasible with promising results for the management of rectal variceal hemorrhage.

Double Tips for In-Plane Polarized Near-Field Microscopy and Spectroscopy.

Near-field optical microscopy and spectroscopy provide high-resolution imaging below the diffraction limit, crucial in physics, chemistry, and biology for studying molecules, nanoparticles, and viruses. These techniques use a sharp metallic tip of an atomic force microscope (AFM) to enhance incoming and scattered light by excited near-fields at the tip apex, leading to high sensitivity and a spatial resolution of a few nanometers. However, this restricts the near-field orientation to out-of-plane polarization, limiting optical polarization choices. We introduce double tips that offer in-plane polarization for enhanced imaging and spectroscopy. These double tips provide superior enhancement over single tips, although with a slightly lower spatial resolution (∼30 nm). They enable advanced studies of nanotubes, graphene defects, and transition metal dichalcogenides, benefiting from polarization control. The double tips allow varied polarization in tip-enhanced Raman scattering and selective excitation of transverse-electric and -magnetic polaritons, expanding the range of nanoscale samples that can be studied.

Seven quick tips for gene-focused computational pangenomic analysis.

Pangenomics is a relatively new scientific field which investigates the union of all the genomes of a clade. The word pan means everything in ancient Greek; the term pangenomics originally regarded genomes of bacteria and was later intended to refer to human genomes as well. Modern bioinformatics offers several tools to analyze pangenomics data, paving the way to an emerging field that we can call computational pangenomics. Current computational power available for the bioinformatics community has made computational pangenomic analyses easy to perform, but this higher accessibility to pangenomics analysis also increases the chances to make mistakes and to produce misleading or inflated results, especially by beginners. To handle this problem, we present here a few quick tips for efficient and correct computational pangenomic analyses with a focus on bacterial pangenomics, by describing common mistakes to avoid and experienced best practices to follow in this field. We believe our recommendations can help the readers perform more robust and sound pangenomic analyses and to generate more reliable results.

Endoscopic clipping combined with cyanoacrylate injection vs. transjugular intrahepatic portosystemic shunt in the treatment of isolated gastric variceal bleeding: Randomized controlled trial.

OBJECTIVES: Although the incidence of isolated gastric varices type 1 (IGV1) bleeding is low, the condition is highly dangerous and associated with high mortality, making its treatment challenging. We aimed to compare the safety and efficacy of endoscopic clipping combined with cyanoacrylate injection (EC-CYA) vs. transjugular intrahepatic portosystemic shunt (TIPS) in treating IGV1. METHODS: In a single-center, randomized controlled trial, patients with IGV1 bleeding were randomly assigned to the EC-CYA group or TIPS group. The primary end-points were gastric variceal rebleeding rates and technical success. Secondary end-points included cumulative nonbleeding rates, mortality, and complications. RESULTS: A total of 156 patients between January 2019 and April 2023 were selected and randomly assigned to the EC-CYA group (n = 76) and TIPS group (n = 80). The technical success rate was 100% for both groups. The rebleeding rates were 14.5% in the EC-CYA group and 8.8% in the TIPS group, showing no significant difference (P = 0.263). Kaplan-Meier analysis revealed that the cumulative nonbleeding rates at 6, 12, 24, and 36 months for the two groups lacked statistical significance (P = 0.344). Similarly, cumulative survival rates at 12, 24, and 36 months for the two groups were not statistically significant (P = 0.916). The bleeding rates from other causes were 13.2% and 6.3% for the respective groups, showing no significant difference (P = 0.144). No instances of ectopic embolism were observed in either group. The incidence of hepatic encephalopathy (HE) in the TIPS group was statistically higher than that in the EC-CYA group (P = 0.001). CONCLUSION: Both groups are effective in controlling IGV1 bleeding. Notably, EC-CYA did not result in ectopic embolism, and the incidence of HE was lower than that observed with TIPS.

Interventions in Budd-Chiari syndrome: an updated review.

Budd Chiari syndrome is a potentially treatable disease, and imaging is the key to its diagnosis. Clinical presentations may vary, ranging from asymptomatic to fulminant disease. Subacute BCS is the most common type encountered in clinical practice, characterized by ascites, hepatosplenomegaly, dilated abdominal wall veins, and varicosities in the lower limb and scrotum. While hepatic vein thrombosis is the leading cause in the West, membranous and short segmental occlusion are predominant in the Asian populations. These geographical variations have an impact on the treatment algorithm in managing BCS. Anticoagulation alone often fails to prevent disease progression, demanding further interventional therapy. Interventional therapy carries a lower morbidity and mortality than surgery. Anatomical recanalization and portosystemic shunting form the basis of endovascular management. Membranous or short-segment occlusion are best treated by angioplasty, which restores the physiological venous outflow and possibly disease reversal. Suboptimal results with angioplasty require stenting. Transjugular intrahepatic shunt (TIPS) or direct IVC to portal vein shunt (DIPS) decompresses the portal pressure and reduces the sinusoidal congestion, which in turn diminishes hepatocellular damage and hepatic fibrosis. Despite its ability to modify the disease course, TIPS carries several procedure and shunt-related complications, mainly hepatic encephalopathy. Thus, anatomical recanalization precedes TIPS in the traditional step-up approach in managing BCS. However, this concept is challenged by some authors, necessitating future reseach. TIPS is a valid bridge therapy in BCS with acute live failure awaiting liver transplantation. Despite all, interventional therapies fail in a subset of BCS patients, leaving them with only option of liver transplantation.

Successful Treatment of Very Severe Sinusoidal Obstruction Syndrome After Gemtuzumab Ozogamicin With Transjugular Intrahepatic Portosystemic Shunt, Defibrotide, and High-Dose Corticosteroids: A Case Report.

Sinusoidal obstruction syndrome (SOS) is a rare but potentially life-threatening complication, usually described in the setting of hematopoietic stem cell transplantation (HSCT). The very severe forms have a high mortality rate (>80%) and need fast recognition and urgent treatment. In this case report, we describe a unique and successful treatment strategy. We present a 27-year-old patient with newly diagnosed CD33+ acute myeloid leukemia (AML). She was treated with induction chemotherapy (7+3 regimen) and gemtuzumab ozogamicin (GO). In the absence of other major risk factors, she developed a very severe SOS with multiple organ failure. She was successfully treated with the urgent insertion of a transjugular intrahepatic portosystemic shunt (TIPS), defibrotide, and high-dose corticosteroids. This case of successful treatment for very severe SOS supports a combination strategy involving the immediate mechanical reduction of portal hypertension through TIPS and drug-mediated inhibition of microvascular thrombosis. Furthermore, this case shows the need for an improved prevention strategy, including the identification of additional risk factors and biomarkers.

Predictors of Duration of Transjugular Intrahepatic Portosystemic Shunt (TIPS) Procedure: A Retrospective Single-Center Study.

PURPOSE: To determine the relationship between clinical, procedural, hospital, and physician characteristics with the duration of the transjugular intrahepatic portosystemic shunt (TIPS) procedure. METHODS: This retrospective study included patients over 18 years of age who underwent an initial TIPS procedure between January 2005 and August 2020. Exclusion criteria were TIPS performed outside the institution and failed TIPS placement. A total of 154 records were included. Regression analyses were used to identify predictors of procedural duration. RESULTS: The mean age at TIPS placement was 57 years. Seventy percent of patients were male and non-Hispanic whites (80.5%). The mean duration of the TIPS procedure was 169 minutes (SD: 78). Procedural duration was shorter when the etiology of cirrhosis was viral (mean: 144 min, SD: 84, p=0.008); the reason for TIPS was ascites (152, SD: 66, p=0.01); and the procedure did not require additional access (153 min, SD: 67, p=<.0001). The main clinical predictor of procedural duration was baseline bilirubin (Beta coefficient (ß): 5.6 min, p=0.0007). In multivariable linear models, in those patients that did not require additional access, bilirubin (ß: 4.9 min, p=0.005), etiology of cirrhosis, and physician experience were the main predictors of TIPS procedure duration. The effect of baseline bilirubin on procedural duration increased in the ascites group (ß: 19.5 minutes, p=0.006), especially when additional access was not required. CONCLUSIONS:  The study demonstrates an association between baseline bilirubin, etiology of cirrhosis, and physician experience with the duration of the TIPS procedure. The mechanism underlying the positive association between baseline bilirubin and procedural time is possibly related to the degree of liver fibrosis.

EuroQol Toddler and Infant Populations (EQ-TIPS): Age-Related Differences in Performance.

OBJECTIVES: The EQ-TIPS was developed to measure the Health-Related Quality of Life in infants/toddlers. Considering the rapid development in this period, this study aimed to investigate age-related variations in EQ-TIPS performance. METHODS: Data from 551 infants/toddlers living with a health condition were analysed. Infants/toddlers were grouped by age: 0-6 months (n = 100), 6-12 months (n = 95), 12-24 months (n = 147), and 36-48 months (n = 97). Differences in item responses and item correlations across age groups were calculated by Kruskal-Wallis and Spearman's correlations, respectively. RESULTS: The report of problems was significantly higher for movement, play, and communication in the 36-48-month group compared to the 0-6-month group. There were strong correlations (r > 0.50) across all age groups between play and movement and communication and social interaction/play; neither pain nor eating showed a clear pattern of association. CONCLUSIONS: There is an age-related difference in the reporting of items linked to developmental milestones (movement, play, and communication) with most problems reported in the 36-48-month group when deviation from peers and continued dependence on caregivers is notable. Consideration should be given to including broader examples of play in the EQ-TIPS. Redefining the items to represent social communication and/or (social) emotion, rather than communication and social interaction, may be warranted. Future research should explore the psychometric performance of items to further inform item inclusion and/or revision.

Discovering genes and microRNAs involved in human lung development unveils IGFBP3/miR-34a dynamics and their relevance for alveolar differentiation.

BACKGROUND: During pseudoglandular stage of the human lung development the primitive bronchial buds are initially conformed by simple tubules lined by endoderm-derived epithelium surrounded by mesenchyme, which will progressively branch into airways and start to form distal epithelial saculles. For first time alveolar type II (AT2) pneumocytes appears. This study aims to characterize the genes and microRNAs involved in this differentiation process and decipher its role in the starting alveolar differentiation. METHODS: Gene and microRNA profiling was performed in human embryonic lungs from 7 to 12 post conception weeks (pcw). Protein expression location of candidate genes were analyzed by immunofluorescense in embryonic lung tissue sections. mRNA/miRNA target pairs were identified using computational approaches and their expression was studied in purified epithelial/mesenchymal cell populations and in isolated tips and stalks from the bronchial tree. Additionally, silencing experiments in human embryonic lung mesenchymal cells and in human embryonic tip-derived lung organoids were performed, as well as organoid differentiation studies. AT2 cell markers were studied by qRT-PCR and by immunofluorescence. The TGFB-ß phosphorylated pathways was analyzed with membrane protein arrays. Lung explants were cultured in air/liquid interface with/without peptides. RESULTS: We identified 88 differentially expressed genes, including IGFBP3. Although IGFBP3 mRNA was detected in both epithelial and mesenchymal populations, the protein was restricted to the epithelium, indicating post-transcriptional regulation preventing IGFBP3 protein expression in the mesenchyme. MicroRNA profiling identified miR-34a as an IGFBP3 regulator. miR-34a was up-regulated in mesenchymal cells, and its silencing in human embryonic lung mesenchymal cells increased IGFBP3 levels. Additionally, IGFBP3 expression showed a marked downregulation from 7 to 12 pcw, suggesting its involvement in the differentiation process. The differentiation of human tip-derived lung embryonic organoids showed a drastic reduction in IGFBP3, supported by the scRNAseq data. IGFBP3 silencing in organoids activated an alveolar-like differentiation process characterized by stem cell markers downregulation and upregulation of AT2 markers. This process was mediated by TGFß signalling inhibition and BMP pathway activation. CONCLUSIONS: The IGFBP3/miR-34a axis restricts IGFBP3 expression in the embryonic undifferentiated lung epithelium, and the progressive downregulation of IGFBP3 during the pseudoglandular stage is required for alveolar differentiation.