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1.
Asian J Urol ; 11(2): 261-270, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38680594

ABSTRACT

Objective: To assess if there is a preferable intervention between retrograde ureteral stent (RUS) and percutaneous nephrostomy (PCN) tube, in cases of upper urinary tract stone obstruction with complications requiring urgent drainage, by evaluating outcomes regarding urinary symptoms, quality of life (QoL), spontaneous stone passage, and length of hospital stays, since there is no literature stating the superiority of one modality over the other. Methods: We searched MEDLINE and other sources for relevant articles in June 2019 without any date restrictions or filters applied. The selection was done first by the title and abstract screening and then by full-text assessment for eligibility. Only randomized controlled trials or cohort studies in patients with hydronephrosis secondary to obstructive urolithiasis that presented comparative data between PCN and RUS placement concerning at least one of the defined outcome measures were included. Lastly, MEDLINE database and PubMed platform were screened again using the same terms, from June 2019 until November 2022. Results: Of 556 initial articles, seven were included in this review. Most works were considered of moderate-to-high quality. Three studies regarding QoL showed a tendency against stenting, even though only one demonstrated statistically significant negative impact on overall health state. Two works reported significantly more post-intervention urinary symptoms in stenting patients. One article found that PCN is a significant predictor of spontaneous stone passage, when adjusted for stone size and location. Findings on length of hospital stays were not consistent among articles. Conclusion: PCN appears to be the intervention better tolerated, with less impact on the patient's perceived QoL and less post-operative urinary symptoms, in comparison with RUS. Nevertheless, further studies with larger samples and a randomized controlled design are suggested.

2.
Elife ; 122024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546191

ABSTRACT

We herein introduce voyAGEr, an online graphical interface to explore age-related gene expression alterations in 49 human tissues. voyAGEr offers a visualisation and statistical toolkit for the finding and functional exploration of sex- and tissue-specific transcriptomic changes with age. In its conception, we developed a novel bioinformatics pipeline leveraging RNA sequencing data, from the GTEx project, encompassing more than 900 individuals. voyAGEr reveals transcriptomic signatures of the known asynchronous ageing between tissues, allowing the observation of tissue-specific age periods of major transcriptional changes, associated with alterations in different biological pathways, cellular composition, and disease conditions. Notably, voyAGEr was created to assist researchers with no expertise in bioinformatics, providing a supportive framework for elaborating, testing and refining their hypotheses on the molecular nature of human ageing and its association with pathologies, thereby also aiding in the discovery of novel therapeutic targets. voyAGEr is freely available at https://compbio.imm.medicina.ulisboa.pt/app/voyAGEr.


Subject(s)
Gene Expression Profiling , Transcriptome , Humans , Gene Expression Regulation , Computational Biology , Sequence Analysis, RNA
3.
RNA ; 30(4): 337-353, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38278530

ABSTRACT

Next-generation RNA sequencing allows alternative splicing (AS) quantification with unprecedented resolution, with the relative inclusion of an alternative sequence in transcripts being commonly quantified by the proportion of reads supporting it as percent spliced-in (PSI). However, PSI values do not incorporate information about precision, proportional to the respective AS events' read coverage. Beta distributions are suitable to quantify inclusion levels of alternative sequences, using reads supporting their inclusion and exclusion as surrogates for the two distribution shape parameters. Each such beta distribution has the PSI as its mean value and is narrower when the read coverage is higher, facilitating the interpretability of its precision when plotted. We herein introduce a computational pipeline, based on beta distributions accurately modeling PSI values and their precision, to quantitatively and visually compare AS between groups of samples. Our methodology includes a differential splicing significance metric that compromises the magnitude of intergroup differences, the estimation uncertainty in individual samples, and the intragroup variability, being therefore suitable for multiple-group comparisons. To make our approach accessible and clear to both noncomputational and computational biologists, we developed betAS, an interactive web app and user-friendly R package for visual and intuitive differential splicing analysis from read count data.


Subject(s)
Alternative Splicing , Software , RNA Splicing , Sequence Analysis, RNA/methods , High-Throughput Nucleotide Sequencing/methods
6.
Int J Mol Sci ; 24(7)2023 Mar 29.
Article in English | MEDLINE | ID: mdl-37047406

ABSTRACT

Traumatic spinal cord injury (SCI) initiates a cascade of cellular events, culminating in irreversible tissue loss and neuroinflammation. After the trauma, the blood vessels are destroyed. The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, is disrupted, facilitating the infiltration of immune cells, and contributing to a toxic spinal microenvironment, affecting axonal regeneration. Understanding how the vascular constituents of the BSCB respond to injury is crucial to prevent BSCB impairment and to improve spinal cord repair. Here, we focus our attention on the vascular transcriptome at 3- and 7-days post-injury (dpi), during which BSCB is abnormally leaky, to identify potential molecular players that are injury-specific. Using the mouse contusion model, we identified Cd9 and Mylip genes as differentially expressed at 3 and 7 dpi. CD9 and MYLIP expression were injury-induced on vascular cells, endothelial cells and pericytes, at the injury epicentre at 7 dpi, with a spatial expression predominantly at the caudal region of the lesion. These results establish CD9 and MYLIP as two new potential players after SCI, and future studies targeting their expression might bring promising results for spinal cord repair.


Subject(s)
Endothelial Cells , Spinal Cord Injuries , Mice , Animals , Endothelial Cells/metabolism , Spinal Cord/metabolism , Spinal Cord Injuries/metabolism , Pericytes/metabolism , Disease Models, Animal , Gene Expression Profiling , Blood-Brain Barrier/metabolism
7.
Respir Med ; 206: 107087, 2023 01.
Article in English | MEDLINE | ID: mdl-36525854

ABSTRACT

INTRODUCTION: This study assessed the test-retest reliability/agreement and construct validity of the International Physical Activity Questionnaire short-form (IPAQ-sf) in patients with chronic obstructive pulmonary disease (COPD). It also explored differences in its validity according to age, sex and GOLD airflow obstruction levels. METHODS: 62 participants (68 ± 8 years, 53 males, FEV1 51 ± 23%pred) completed the Portuguese IPAQ-sf, wore an accelerometer for 7 days and completed a second IPAQ-sf. Test-retest reliability/agreement was assessed with Intraclass Correlation Coefficient (ICC2,1), 95% Limits of Agreement (LoA), standard error of measurement (SEM) and minimal detectable change (MDC95) for continuous variables, and percentage of agreement (%agreement) for categories ("active"/"inactive"). Validity was assessed with 95% LoA and Spearman's correlations (ρ) between IPAQ-sf 2 (METs-min/week, time in vigorous [VPA], moderate PA [MPA] and walking) and accelerometry (time in MVPA, VPA, MPA and step counts) for continuous variables; %agreement, Cohen's kappa, and sensitivity specificity and±predictive values for categories. Correlations were also performed for age, sex and GOLD airflow obstruction grades. RESULTS: Reliability was good (ICC2,1 = 0.707) with wide LoA (-6446-6409 METs-min/week). SEM and MDC95 were 1840 and 4971 METs-min/week, respectively. %agreement between the two IPAQ-sf was 84% (kappa = 0.660). Positive, moderate and significant correlations were found between IPAQ-sf and accelerometry (0.396 ≤ ρ ≤ 0.527, p < 0.001), except for VPA (p > 0.05). The strongest correlations were found in age (<65 years) and male (0.466 ≤ ρ ≤ 0.653, p < 0.05). %agreement between tools was 65% (kappa = 0.313), with high sensitivity (0.830) but low specificity (0.500). CONCLUSIONS: The IPAQ-sf seems valid to be used in COPD but caution on its widespread use is recommended as its accuracy may be limited.


Subject(s)
Exercise , Pulmonary Disease, Chronic Obstructive , Humans , Male , Aged , Surveys and Questionnaires , Reproducibility of Results , Walking
8.
J Surg Case Rep ; 2022(9): rjac419, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36196128

ABSTRACT

Entero-neovesical fistula is a rare complication of orthotopic ileal neobladder after radical cystectomy occurring in <2% of cases. Surgical treatment is usually required and includes open resection of the affected bowel tract and reconstitution of bowel transit. Here we present a case of a laparoscopic treatment of entero-to-neobladder fistula 8 years after laparoscopic radical cystectomy to demonstrate the feasibility and safety of minimally invasive treatment (Supplementary Video). To the best of our knowledge, this is the first report of minimally invasive treatment of entero-neobladder fistula.

9.
Artif Intell Med ; 126: 102275, 2022 04.
Article in English | MEDLINE | ID: mdl-35346444

ABSTRACT

This paper confronts two approaches to classify bladder lesions shown in white light cystoscopy images when using small datasets: the classical one, where handcrafted-based features feed pattern recognition systems and the modern deep learning-based (DL) approach. In between, there are alternative DL models that had not received wide attention from the scientific community, even though they can be more appropriate for small datasets such as the human brain motivated capsule neural networks (CapsNets). However, CapsNets have not yet matured hence presenting lower performances than the most classic DL models. These models require higher computational resources, more computational skills from the physician and are more prone to overfitting, making them sometimes prohibitive in the routine of clinical practice. This paper shows that carefully handcrafted features used with more robust models can reach similar performances to the conventional DL-based models and deep CapsNets, making them more useful for clinical applications. Concerning feature extraction, it is proposed a new feature fusion approach for Ta and T1 bladder tumor detection by using decision fusion from multiple classifiers in a scheme known as stacking of classifiers. Three Neural Networks perform classification on three different feature sets, namely: Covariance of Color Histogram of Oriented Gradients, proposed in the ambit of this paper; Local Binary Patterns and Wavelet Coefficients taken from lower scales. Data diversity is ensured by a fourth Neural Network, which is used for decision fusion by combining the outputs of the ensemble elements to produce the classifier output. Both Feed Forward Neural Networks and Radial Basis Functions are used in the experiments. Contrarily, DL-based models extract automatically the best features at the cost of requiring huge amounts of training data, which in turn can be alleviated by using the Transfer Learning (TL) strategy. In this paper VGG16 and ResNet-34 pretrained in ImageNet were used for TL, slightly outperforming the proposed ensemble. CapsNets may overcome CNNs given their ability to deal with objects rotational invariance and spatial relationships. Therefore, they can be trained from scratch in applications using small amounts of data, which was beneficial for the current case, improving accuracy from 94.6% to 96.9%.


Subject(s)
Urinary Bladder Neoplasms , Female , Humans , Machine Learning , Male , Neural Networks, Computer , Pattern Recognition, Automated , Urinary Bladder Neoplasms/diagnosis
10.
Support Care Cancer ; 30(7): 5601-5613, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35107601

ABSTRACT

PURPOSE: To investigate the effects of exercise training on cancer-related fatigue (CRF) in colorectal cancer survivors. METHODS: Randomized controlled trials published between 1 January 2010 and 19 October 2020, selected through online search conducted in PubMed, Scopus, Web of Science, SPORTDiscus and PEDro databases, were included. Eligible trials compared the effect of exercise training interventions, versus non-exercise controls on CRF, in colorectal cancer survivors, during or after treatment. The methodological quality of individual studies was analysed using the Physiotherapy Evidence Database (PEDro) scale. Standardized mean differences (SMD) that were pooled using random-effects models were included as the effect size. In addition, 95% prediction intervals (PI) were calculated. RESULTS: Six trials involving 330 colorectal cancer patients met the inclusion criteria and presented reasonable to good methodological quality. An overall small-to-moderate effect of exercise training on CRF was found (SMD = - 0.29: 95% CI: [- 0.53; - 0.06]; p = 0.01; PI: [- 0.63; 0.04]; low-quality evidence). Subgroup analysis revealed moderate effects of exercise interventions performed during chemotherapy (SMD = - 0.63; 95% CI: [- 1.06; - 0.21]; p = 0.003) and small, non-significant effects, when exercise training was performed after cancer treatment (SMD = - 0.14; 95% CI: [- 0.43; 0.14]; p = 0.32). Steady improvements were achieved when a combination of aerobic plus resistance exercise was used, in interventions lasting 12 to 24 weeks. CONCLUSION: Exercise training could be regarded as a supportive therapy for the clinical management of CRF in colorectal cancer patients undergoing chemotherapy, but further studies are necessary to clarify the effects of exercise interventions on CRF after cancer treatment.


Subject(s)
Colorectal Neoplasms , Quality of Life , Colorectal Neoplasms/complications , Colorectal Neoplasms/therapy , Exercise , Exercise Therapy , Fatigue/etiology , Fatigue/therapy , Humans , Randomized Controlled Trials as Topic , Survivors
11.
J Clin Med ; 10(23)2021 Nov 29.
Article in English | MEDLINE | ID: mdl-34884333

ABSTRACT

Motivation can be broadly defined as what moves people to act. Low motivation is a frequently reported factor for the reduced physical activity (PA) levels observed in patients with chronic obstructive pulmonary disease (COPD). This study assessed patients' motives to be physically active, according to three pulmonary rehabilitation (PR) participation groups (Never PR, Previous PR and Current PR) and explored whether these motives were related to the PA levels and clinical characteristics. The motives to be physically active were assessed with the Exercise Motivation Inventory-2 (EMI-2, 14 motivational factors, five dimensions) and PA with accelerometry (PA groups: <5000 steps/day vs. ≥5000 steps/day). The clinical variables included symptoms, impact of the disease, exercise capacity and comorbidities. Ninety-two patients (67.4 ± 8.1 years, 82.6% male, forced expiratory volume in 1s (FEV1) 48.3 ± 18.9% predicted; 30.4% Never PR, 51% Previous PR and 18.5% Current PR) participated. The motivational dimensions related to health/fitness presented the highest scores (3.8 ± 1.1; 3.4 ± 1.3). The motives to be active were not significantly different between PA groups (p > 0.05) but having less symptoms and ≥two comorbidities were associated with higher scores in psychological/health and body-related motives, respectively (p < 0.05). The findings may encourage health professionals to actively explore with patients their motives to be physically active to individualise PA promotion.

12.
ACS Cent Sci ; 7(5): 868-881, 2021 May 26.
Article in English | MEDLINE | ID: mdl-34079902

ABSTRACT

The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. The structure of the PL-bound full-length rat TRPV2 channel was determined by cryo-EM. PL binds to a transient allosteric pocket responsible for a new mode of anticancer activity against glioblastoma (GBM) in which hTRPV2 is overexpressed. Calcium imaging experiments revealed the importance of Arg539 and Thr522 residues on the antagonistic effect of PL and calcium influx modulation of the TRPV2 channel. Downregulation of hTRPV2 reduces sensitivity to PL and decreases ROS production. Analysis of GBM patient samples associates hTRPV2 overexpression with tumor grade, disease progression, and poor prognosis. Extensive tumor abrogation and long term survival was achieved in two murine models of orthotopic GBM by formulating PL in an implantable scaffold/hydrogel for sustained local therapy. Furthermore, in primary tumor samples derived from GBM patients, we observed a selective reduction of malignant cells in response to PL ex vivo. Our results establish a broadly applicable strategy, leveraging data-motivated research hypotheses for the discovery of novel means tackling cancer.

13.
Nat Commun ; 12(1): 3153, 2021 05 26.
Article in English | MEDLINE | ID: mdl-34039990

ABSTRACT

RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csbm/m developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for transcription-coupled DNA repair disorders.


Subject(s)
DNA Repair , DNA-Binding Proteins/metabolism , Endonucleases/metabolism , Nuclear Proteins/metabolism , RNA Splicing Factors/metabolism , Transcription Factors/metabolism , Animals , Cell Line , DNA Damage/drug effects , Female , Gene Expression Regulation, Developmental , Gene Knock-In Techniques , Gene Knockdown Techniques , Liver/growth & development , Liver/metabolism , Male , Mice , Mice, Transgenic , Mouse Embryonic Stem Cells , Polycyclic Sesquiterpenes/pharmacology , R-Loop Structures/genetics , RNA Precursors/genetics , RNA Precursors/metabolism , RNA Splicing Factors/genetics , RNA, Small Nuclear , RNA-Seq , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Spliceosomes/metabolism , Transcription, Genetic
14.
Cent European J Urol ; 74(1): 131-138, 2021.
Article in English | MEDLINE | ID: mdl-33976929

ABSTRACT

INTRODUCTION: This study aimed to compare trainees' laparoscopic performance concerning the peg-transfer (PT) and needle-guidance (NG) exercises after watching the original European Basic Laparoscopic Urologic Skills (E-BLUS) video or after watching a video-mentored tutorial (VMT) with 'tips and tricks', narration and didactic illustrations. MATERIAL AND METHODS: An experimental, unblinded, parallel, 2-intervention, 2-period randomized trial with an allocation ratio of 1:1 was conducted. Forty-two participants were randomized into 2 groups. Prior to task initiation, Group 1 watched the VMT in both trials and Group 2 watched, firstly, the original E-BLUS examination video and, in the second trial, the VMT. Each participant performed 2 trials for each exercise. Outcome measures were task time and total number of errors. RESULTS: In the first period, participants who visualized the PT and NG VMT had fewer errors than participants who visualized the E-BLUS video (p = 0.001 and p = 0.014, respectively). In the second period, after watching the VMT, a decrease in the total number of errors in PT and NG exercises was observed in the participants who previously watched the E-BLUS video (p = 0.001 and p = 0.002, respectively). In the second period, a decrease in median task time was observed for Group 1 and 2 after watching the PT VMT (p ≤0.001 and p = 0.003, respectively) and NG VMT (p = 0.005 and p = 0.01, respectively). CONCLUSIONS: The use of VMT can lead to a smaller number of errors and, if coupled with deliberate practice, could lead to a shorter task time in exercise performance among participants with no previous laparoscopic experience.

15.
Front Rehabil Sci ; 2: 729237, 2021.
Article in English | MEDLINE | ID: mdl-36188799

ABSTRACT

Effectiveness of technology-based interventions to improve physical activity (PA) in people with COPD is controversial. Mixed results may be due to participants' characteristics influencing their use of and engagement with mobile health apps. This study compared demographic, clinical, physical and PA characteristics of patients with COPD using and not using mobile apps in daily life. Patients with COPD who used smartphones were asked about their sociodemographic and clinic characteristics, PA habits and use of mobile apps (general and PA-related). Participants performed a six-minute walk test (6MWT), gait speed test and wore an accelerometer for 7 days. Data were compared between participants using (App Users) and not using (Non-App Users) mobile apps. A sub-analysis was conducted comparing characteristics of PA-App Users and Non-Users. 59 participants were enrolled (73% Male; 66.3 ± 8.3 yrs; FEV1 48.7 ± 18.4% predicted): 59% were App Users and 25% were PA-App Users. Significant differences between App Users and Non-App Users were found for age (64.2 ± 8.9 vs. 69.2 ± 6.3yrs), 6MWT (462.9 ± 91.7 vs. 414.9 ± 82.3 m), Gait Speed (Median 1.5 [Q1-Q3: 1.4-1.8] vs. 2.0 [1.0-1.5]m/s), Time in Vigorous PA (0.6 [0.2-2.8] vs. 0.14 [0.1-0.7]min) and Self-Reported PA (4.0 [1.0-4.0] vs. 1.0 [0.0-4.0] Points). Differences between PA-App Users and Non-Users were found in time in sedentary behavior (764.1 [641.8-819.8] vs. 672.2 [581.2-749.4] min) and self-reported PA (4.0 [2.0-6.0] vs. 2.0 [0.0-4.0] points). People with COPD using mobile apps were younger and had higher physical capacity than their peers not using mobile apps. PA-App Users spent more time in sedentary behaviors than Non-Users although self-reporting more time in PA.

16.
Front Neurosci ; 14: 607215, 2020.
Article in English | MEDLINE | ID: mdl-33362460

ABSTRACT

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders worldwide, with age being their major risk factor. The increasing worldwide life expectancy, together with the scarcity of available treatment choices, makes it thus pressing to find the molecular basis of AD and PD so that the causing mechanisms can be targeted. To study these mechanisms, gene expression profiles have been compared between diseased and control brain tissues. However, this approach is limited by mRNA expression profiles derived for brain tissues highly reflecting their degeneration in cellular composition but not necessarily disease-related molecular states. We therefore propose to account for cell type composition when comparing transcriptomes of healthy and diseased brain samples, so that the loss of neurons can be decoupled from pathology-associated molecular effects. This approach allowed us to identify genes and pathways putatively altered systemically and in a cell-type-dependent manner in AD and PD brains. Moreover, using chemical perturbagen data, we computationally identified candidate small molecules for specifically targeting the profiled AD/PD-associated molecular alterations. Our approach therefore not only brings new insights into the disease-specific and common molecular etiologies of AD and PD but also, in these realms, foster the discovery of more specific targets for functional and therapeutic exploration.

17.
RNA ; 26(12): 1935-1956, 2020 12.
Article in English | MEDLINE | ID: mdl-32963109

ABSTRACT

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the Drosophila ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of gurken Germline depletion of Salsa and splice site mutations within gurken first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal-ventral patterning defects observed after Salsa depletion could be suppressed by the expression of a gurken construct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron of gurken mRNA. Retention of gurken first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.


Subject(s)
Body Patterning/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/physiology , Gene Expression Regulation, Developmental , Introns/genetics , RNA Splicing , Transforming Growth Factor alpha/metabolism , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila Proteins/genetics , Female , Infertility, Female/etiology , Infertility, Female/metabolism , Infertility, Female/pathology , Spliceosomes/genetics , Spliceosomes/metabolism , Transforming Growth Factor alpha/genetics
18.
Oncotarget ; 11(19): 1714-1728, 2020 May 12.
Article in English | MEDLINE | ID: mdl-32477461

ABSTRACT

The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)-positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cell cycle regulators and decreases sensitivity to fulvestrant of estrogen receptor (ER)-positive (ER+)/HER2- breast cancer cells, MCF-7 and T47D. Moreover, RANK overexpressing cells had a staminal and mesenchymal phenotype, with decreased proliferation rate and decreased susceptibility to chemotherapy, but were more invasive in vivo. In silico analysis of the transcriptome of human breast tumors, confirmed the association between RANK expression and stem cell and mesenchymal markers in ER+HER2- tumors. Importantly, exposure of ER+HER2- cells to continuous RANK pathway activation by exogenous RANKL, in vitro and in vivo, induced a negative feedback effect, independent of RANK levels, leading to the downregulation of HR and increased resistance to hormone therapy. These results suggest that ER+HER2- RANK-positive cells may constitute an important reservoir of slow cycling, therapy-resistance cancer cells; and that RANK pathway activation is deleterious in all ER+HER2- breast cancer cells, independently of RANK levels.

19.
Allergy ; 75(9): 2309-2318, 2020 09.
Article in English | MEDLINE | ID: mdl-32248566

ABSTRACT

BACKGROUND: Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy. OBJECTIVE: To identify differences in IgE and IgG4 binding to peanut peptides between peanut-allergic (PA) and peanut-sensitized but tolerant (PS) children. METHODS: PA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15-mer peptides of peanut allergens (Ara h 1-11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood-ratio tests between each specified nominal logistic regression models. RESULTS: Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2-specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. CONCLUSIONS: Ara h 2 peptide-specific IgE added diagnostic value to Ara h 2-specific IgE. Ability of peptide-specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance.


Subject(s)
Antigens, Plant , Peanut Hypersensitivity , 2S Albumins, Plant , Allergens , Arachis , Child , Epitopes , Humans , Immunoglobulin E , Peanut Hypersensitivity/diagnosis , Plant Proteins
20.
Minerva Urol Nefrol ; 72(5): 629-636, 2020 Oct.
Article in English | MEDLINE | ID: mdl-31920064

ABSTRACT

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is the gold-standard for treatment of renal stones larger than 20 mm. Traditionally, a nephrostomy tube (NT) is placed, causing discomfort and prolonged hospitalization but some surgeons prefer the tubeless technique (TL). Simultaneously, the effectiveness of ureteral stents after PNCL is doubtful. We investigated the safety of the TL technique as well as that of the single loop (SL) over double loop (DL) stents. METHODS: Three hundred and twenty-one individuals submitted to PCNL in a single center were retrospectively reviewed. Statistical analysis was performed to compare procedures regarding safety and effectiveness (stone size, residual stones, operative time, peri- and post-operative complications, need for blood transfusion and length of hospital stay) between two groups regarding presence or absence of NT placement (NT [N.=198] vs. TL [N.=123]); and according to the type of stent used (SL [N.=74] vs. DL [N.=247]). RESULTS: NT was associated with a higher complications rate compared to the TL (30.3% and 13%, respectively; P=0.001) and longer hospitalization (4 vs. 2 days; P=0.001). Regarding ureteral stents, they cause similar morbidities (20.7% and 24.4%; P=0.881), and median length of stay (3 days; P=0.947). NT and DL were more frequent in patients with higher stone burden. CONCLUSIONS: Tubeless PCNL encompasses lower morbidity and should be considered as an option for select patients, particularly with less stone burden and uncomplicated procedures. Regarding ureteral stents, SL is a safe option and does not require further procedures for removal.


Subject(s)
Drainage/adverse effects , Drainage/methods , Nephrolithotomy, Percutaneous/methods , Urinary Calculi/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Length of Stay , Male , Middle Aged , Nephrolithotomy, Percutaneous/adverse effects , Postoperative Complications , Retrospective Studies , Stents , Treatment Outcome , Ureter/surgery , Urinary Catheterization/statistics & numerical data , Young Adult
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