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1.
Nature ; 620(7972): 192-199, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37495690

ABSTRACT

Sympathetic activation during cold exposure increases adipocyte thermogenesis via the expression of mitochondrial protein uncoupling protein 1 (UCP1)1. The propensity of adipocytes to express UCP1 is under a critical influence of the adipose microenvironment and varies between sexes and among various fat depots2-7. Here we report that mammary gland ductal epithelial cells in the adipose niche regulate cold-induced adipocyte UCP1 expression in female mouse subcutaneous white adipose tissue (scWAT). Single-cell RNA sequencing shows that glandular luminal epithelium subtypes express transcripts that encode secretory factors controlling adipocyte UCP1 expression under cold conditions. We term these luminal epithelium secretory factors 'mammokines'. Using 3D visualization of whole-tissue immunofluorescence, we reveal sympathetic nerve-ductal contact points. We show that mammary ducts activated by sympathetic nerves limit adipocyte UCP1 expression via the mammokine lipocalin 2. In vivo and ex vivo ablation of mammary duct epithelium enhance the cold-induced adipocyte thermogenic gene programme in scWAT. Since the mammary duct network extends throughout most of the scWAT in female mice, females show markedly less scWAT UCP1 expression, fat oxidation, energy expenditure and subcutaneous fat mass loss compared with male mice, implicating sex-specific roles of mammokines in adipose thermogenesis. These results reveal a role of sympathetic nerve-activated glandular epithelium in adipocyte UCP1 expression and suggest that mammary duct luminal epithelium has an important role in controlling glandular adiposity.


Subject(s)
Adipocytes , Adipose Tissue, White , Epithelium , Mammary Glands, Animal , Thermogenesis , Animals , Female , Male , Mice , Adipocytes/metabolism , Adipose Tissue, White/cytology , Adipose Tissue, White/metabolism , Epithelium/innervation , Epithelium/metabolism , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolism , Mammary Glands, Animal/cytology , Mammary Glands, Animal/innervation , Mammary Glands, Animal/physiology , Cold Temperature , Sympathetic Nervous System/physiology , Energy Metabolism , Oxidation-Reduction , Sex Characteristics
2.
Nature ; 596(7872): 357-361, 2021 08.
Article in English | MEDLINE | ID: mdl-34408330

ABSTRACT

Supersolid states simultaneously feature properties typically associated with a solid and with a superfluid. Like a solid, they possess crystalline order, manifesting as a periodic modulation of the particle density; but unlike a typical solid, they also have superfluid properties, resulting from coherent particle delocalization across the system. Such states were initially envisioned in the context of bulk solid helium, as a possible answer to the question of whether a solid could have superfluid properties1-5. Although supersolidity has not been observed in solid helium (despite much effort)6, ultracold atomic gases provide an alternative approach, recently enabling the observation and study of supersolids with dipolar atoms7-16. However, unlike the proposed phenomena in helium, these gaseous systems have so far only shown supersolidity along a single direction. Here we demonstrate the extension of supersolid properties into two dimensions by preparing a supersolid quantum gas of dysprosium atoms on both sides of a structural phase transition similar to those occurring in ionic chains17-20, quantum wires21,22 and theoretically in chains of individual dipolar particles23,24. This opens the possibility of studying rich excitation properties25-28, including vortex formation29-31, and ground-state phases with varied geometrical structure7,32 in a highly flexible and controllable system.

3.
Am J Hum Genet ; 110(10): 1817-1824, 2023 10 05.
Article in English | MEDLINE | ID: mdl-37659414

ABSTRACT

Response to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseases. Using changes in disease activity scores across 5,218 genotyped individuals from 19 clinical trials across four indications (psoriatic arthritis, psoriasis, ankylosing spondylitis, and rheumatoid arthritis), we tested whether genetics predicted response to secukinumab. We did not find any evidence of association between treatment response and common variants, imputed HLA alleles, polygenic risk scores of disease susceptibility, or cross-disease components of shared genetic risk. This suggests that anti-IL17 therapy is equally effective regardless of an individual's genetic background, a finding that has important implications for future genetic studies of biological therapy response in inflammatory diseases.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Psoriasis , Humans , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/genetics , Psoriasis/drug therapy , Psoriasis/genetics , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Genotype
4.
Mol Ther ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822525

ABSTRACT

Single monoclonal antibodies (mAbs) can be expressed in vivo through gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureus first in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice. Intravenous delivery of each mRNA/LNP or the trio (1 mg/kg each) induced functional antibody expression after 24 h (10-100 µg/mL) with 64%-78% cognate-chain paired IgG expression after 3 days, and an absence of non-cognate chain pairing for scFv-Fc. We did not observe reduced neutralizing activity for each mAb compared with the level of expression of chain-paired mAbs. Delivery of the trio mRNA protected mice in an S. aureus-induced dermonecrosis model. Intravenous administration of the three mRNA in non-human primates achieved peak serum IgG levels ranging between 2.9 and 13.7 µg/mL with a half-life of 11.8-15.4 days. These results suggest nucleic acid delivery of mAb combinations holds promise and may be a viable option to streamline the development of therapeutic antibodies.

5.
Nucleic Acids Res ; 51(D1): D1038-D1045, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36305825

ABSTRACT

The International Mouse Phenotyping Consortium (IMPC; https://www.mousephenotype.org/) web portal makes available curated, integrated and analysed knockout mouse phenotyping data generated by the IMPC project consisting of 85M data points and over 95,000 statistically significant phenotype hits mapped to human diseases. The IMPC portal delivers a substantial reference dataset that supports the enrichment of various domain-specific projects and databases, as well as the wider research and clinical community, where the IMPC genotype-phenotype knowledge contributes to the molecular diagnosis of patients affected by rare disorders. Data from 9,000 mouse lines and 750 000 images provides vital resources enabling the interpretation of the ignorome, and advancing our knowledge on mammalian gene function and the mechanisms underlying phenotypes associated with human diseases. The resource is widely integrated and the lines have been used in over 4,600 publications indicating the value of the data and the materials.


Subject(s)
Databases, Factual , Disease Models, Animal , Mice, Knockout , Animals , Humans , Mice , Phenotype
6.
Article in English | MEDLINE | ID: mdl-38782175

ABSTRACT

BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or Normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.

7.
Langmuir ; 2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38343280

ABSTRACT

Thin films of ionic liquids (ILs) have gained significant attention due to their unique properties and broad applications. Extensive research has focused on studying the influence of ILs' chemical composition and substrate characteristics on the structure and morphology of IL films at the nano- and mesoscopic scales. This study explores the impact of carbon-coated surfaces on the morphology and wetting behavior of a series of alkylimidazolium-based ILs. Specifically, this work investigates the effect of carbon coating on the morphology and wetting behavior of short-chain ([C2C1im][NTf2] and [C2C1im][OTf]) and long-chain ([C8C1im][NTf2] and [C8C1im][OTf]) ILs deposited on indium tin oxide (ITO), silver (Ag), and gold (Au) substrates. A reproducible vapor deposition methodology was utilized for the deposition process. High-resolution scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy were used to analyze the morphological and structural characteristics of the substrates and obtained IL films. The experimental data revealed that the IL films deposited on carbon-coated Au substrates showed minor changes in their morphology compared to that of the films deposited on clean Au surfaces. However, the presence of carbon coatings on the ITO and Ag surfaces led to significant morphological alterations in the IL films. Specifically, for short-chain ILs, the carbon film surface induced 2D growth of the IL film, followed by subsequent island growth. In contrast, for long-chain ILs deposited on carbon surfaces, layer-by-layer growth occurred without island formation, resulting in highly uniform and coalesced IL films. The extent of morphological changes observed in the IL films was found to be influenced by two crucial factors: the thickness of the carbon film on the substrate surface and the amount of IL deposition.

8.
J Biomed Inform ; 154: 104641, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642627

ABSTRACT

OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Psoriatic/drug therapy , Longitudinal Studies , Treatment Outcome , Antibodies, Monoclonal, Humanized/therapeutic use , Principal Component Analysis , Clinical Trials as Topic , Clinical Trials, Phase III as Topic , Models, Statistical
9.
J Phys Chem A ; 128(23): 4674-4684, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38815182

ABSTRACT

This work presents a comprehensive study exploring the thermodynamics of the solid phase of a series of phenylimidazoles, encompassing experimental measurements of heat capacity, volatility, and thermal behavior. The influence of successive phenyl group insertions on the imidazole ring on thermodynamic properties and supramolecular behavior was thoroughly examined through the evaluation of 2-phenylimidazole (2-PhI), 4-phenylimidazole (4-PhI), 4,5-diphenylimidazole (4,5-DPhI), and 2,4,5-triphenylimidazole (2,4,5-TPhI). Structural correlations between molecular structure and thermodynamic properties were established. Furthermore, the investigation employed UV-vis spectroscopy and quantum chemical calculations. Additive effects arising from the introduction of phenyl groups were found through the analysis of the solid-liquid and solid-gas equilibria, as well as heat capacities. A good correlation emerged between the thermodynamic properties of sublimation and the molar volume of the unit cell, evident across 2-PhI, 4,5-DPhI, and 2,4,5-TPhI. In contrast to its isomer 2-PhI, 4-PhI exhibited greater cohesive energy due to the stronger N-H···N intermolecular interactions, leading to the disruption of coplanar geometry in the 4-PhI molecules. The observed higher entropies of phase transition (fusion and sublimation) are consistent with the higher structural order observed in the crystalline lattice of 4-PhI.

10.
Transfus Apher Sci ; 63(1): 103876, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38310032

ABSTRACT

Promoting blood donation requires understanding and identifying the factors that motivate donations so that strategies for retaining and increasing loyalty can be developed. Transfusion literacy can be improved through school-based teaching and information about giving and solidarity to promote the development of future donors. For the purpose of aligning any strategies and motivational dynamics that promote adherence to informed donation and loyalty among students in the municipality of Coimbra. This study was undertaken to assess the perception of secondary school teachers regarding the students' knowledge of blood donation. A survey was conducted among teachers from seven public schools in Coimbra with regard to the 3rd and Secondary cycles. Based on the data, people give blood for a feeling of personal satisfaction and peer influence, as well as for the satisfaction of helping others. Blood donation should be made a focal point of relevance and interest in the school community, by implementing programs, projects, and dissemination actions targeting this target group. We are extremely glad and most enthusiastic to be invited to share our study through what's happening with the readers globally.


Subject(s)
Blood Donation , Students , Humans , Perception , Portugal , Schools
11.
Mol Ther ; 31(2): 409-419, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36369741

ABSTRACT

The accumulation of soluble oligomers of the amyloid-ß peptide (AßOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AßOs and shows minimal reactivity to Aß monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AßOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AßO binding to neurons and AßO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AßOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AßO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.


Subject(s)
Alzheimer Disease , Single-Chain Antibodies , Mice , Rats , Humans , Animals , Aged , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Single-Chain Antibodies/genetics , Single-Chain Antibodies/metabolism , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Synapses/metabolism , Neurons/metabolism , Memory Disorders/genetics , Memory Disorders/therapy
12.
Chem Biodivers ; : e202400645, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38923658

ABSTRACT

Antimicrobial films were prepared with chitosan containing the methanolic extract of M. tenuiflora leaves (FECT20%, FECT30%, and FECT40%), and their antimicrobial activities were evaluated by agar diffusion. The films were characterized by IR spectroscopy, scanning electron microscopy (SEM) and TG/DTG curves. TG/DTG curves showed thermal stability of chitosan-extract films up to 166 ºC. Micrographs of chitosan-extract films revealed an increase in porosity with the addition of extract. The FECT40% film showed inhibition zone diameters (IZ) against Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis, and B. cereus, ranging from 1.0 ± 0.02 to 0.72 ± 0.09 cm. Only FECT30% and FECT40% inhibited the P. aeruginosa with IZs of 0.68 ± 0.02 and 0.77 ± 0.06 cm, respectively. In turn, the extract showed inhibition against B. subtilis and B. cereus, with IZs values of 0.92 ± 0.2 cm and 0.72 ± 0.05 cm, respectively. Additionally, the crude extract presented antioxidant potential with inhibition percentages of 32.74% ± 0.90 for ABTS and 27.04% ± 1.36 for DPPH. The antimicrobial and antioxidant activities of the crude extract, as well as the antimicrobial property of chitosan-extract films, suggests the potential of these biopolymers for the development of wound healing bandages and new food packaging alternatives.

13.
J Appl Clin Med Phys ; 25(2): e14245, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38194595

ABSTRACT

PURPOSE: To study the feasibility of using the Integral Quality Monitoring (IQM) system for routine quality assurance (QA) of photon beams. METHODS: The IQM system is a commercially available dose delivery verification tool, which consists of a spatially sensitive large area transmission ion chamber, mounted on the Linac collimator, and a calculation algorithm to predict the signals in response to radiation beams. By comparing the measured and predicted signals the system verifies the accuracy of beam delivery. The ion chamber unit is a battery powered system including a dual-electrometer, temperature and pressure sensors, and inclinometers. The feasibility of using the IQM system for routine QA tests was investigated by measuring constancy values of beam parameters, with specially designed tests fields, and comparing them with those determined by a conventional system. RESULTS: The sensitivity of the beam output constancy measurements by the IQM system was found to agree with those measured by a Farmer type ion chamber placed in water phantoms to within 0.1% for typical daily output variation of ± 0.5% and ± 1%. The beam symmetry was measured with a 4 cm × 4 cm aperture at multiple off-axis distances and was found to have a highly linear relationship with those measured in a water phantom scan for intentionally introduced asymmetry between -3% and +3%. The beam flatness was measured with a two-field ratio method and was found to be linearly correlated with those measured by water phantom scan. The dosimetric equivalent of a picket fence test performed by the IQM system can serve as a constancy check of the multileaf collimator (MLC) bank positioning test. CONCLUSIONS: The IQM system has been investigated for constancy measurements of various beam parameters for photon beams. The results suggest that the system can be used for most of the routine QA tests effectively and efficiently.


Subject(s)
Particle Accelerators , Quality Assurance, Health Care , Humans , Feasibility Studies , Radiometry , Water
14.
Alzheimers Dement ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009473

ABSTRACT

Extracellular vesicles (EVs) hold promise as a source of disease biomarkers. The diverse molecular cargo of EVs can potentially indicate the status of their tissue of origin, even against the complex background of whole plasma. The main tools currently available for assessing biomarkers of brain health include brain imaging and analysis of the cerebrospinal fluid of patients. Given the costs and difficulties associated with these methods, isolation of EVs of neuronal origin (NEVs) from the blood is an attractive approach to identify brain-specific biomarkers. This perspective describes current key challenges in EV- and NEV-based biomarker research. These include the relative low abundance of EVs, the lack of validated isolation methods, and the difficult search for an adequate target for immunocapturing NEVs. We discuss that these challenges must be addressed before NEVs can fulfill their potential for biomarker research. HIGHLIGHTS: NEVs are promising sources of biomarkers for brain disorders. Immunocapturing NEVs from complex biofluids presents several challenges. The choice of surface target for capture will determine NEV yield. Contamination by non-EV sources is relevant for biomarkers at low concentrations.

15.
Int J Mol Sci ; 25(5)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38474124

ABSTRACT

Enteropathogenic Escherichia coli (EPEC) produce a capsule of polysaccharides identical to those composing the O-antigen polysaccharide of its LPS (lipopolysaccharide) molecules. In light of this, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC compared to non-capsulated enterohemorrhagic Escherichia coli (EHEC) was investigated. Our findings reveal that there was no significant difference between the levels in EPEC and EHEC of rhamnose (2.8:2.5), a molecule considered to be a PAMP (Pathogen Associated Molecular Patterns). However, the levels of glucose (10:1.69), heptose (3.6:0.89) and N-acetylglucosamine (4.5:2.10), were significantly higher in EPEC than EHEC, respectively. It was also observed that the presence of a capsule in EPEC inhibited the deposition of C3b on the bacterial surface and protected the pathogen against lysis by the complement system. In addition, the presence of a capsule also protected EPEC against phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies, and additionally, these antibodies were able to inhibit O26 EPEC adhesion to human epithelial cells. Finally, the results indicate that O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the development of a vaccine against capsulated O26 E. coli.


Subject(s)
Enterohemorrhagic Escherichia coli , Enteropathogenic Escherichia coli , Escherichia coli Infections , Escherichia coli Proteins , Humans , Immune Evasion , Escherichia coli Infections/microbiology , Escherichia coli Proteins/pharmacology , Lipopolysaccharides/pharmacology , Vaccine Development
16.
Article in English | MEDLINE | ID: mdl-38358048

ABSTRACT

Dear Editor, We would like to thank Dr. Madias for his valuable comment on our original article entitled "QT interval prolongation in Takotsubo Syndrome: a frightening feature with no major prognostic impact" published in Monaldi Archives for Chest Disease on December 6, 2023...

17.
Rev Esp Enferm Dig ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38345475

ABSTRACT

A man in his 70s, without prior foreign body history, presented to the emergency department 15 days after accidentally inserting a tubular object into his anus. He reported a reduction in normal bowel movements. Initial physical examination was normal. An abdominal X-ray revealed a tubular hypodensity in the pelvic region, without perforation. Subsequently, it was decided to perform a colonoscopy during which a foreign body was visualized in the distal rectum, that was successfully removed with the use of a rat tooth forceps. The foreign body was a plastic tube about 18cm in size. Afterwards, the rest of the colon was assessed, having identified an ulcer in the lower rectum related to the presence of the object. Six months later, the patient reported no complains and a follow-up colonoscopy was conducted which was normal. Discussion: Rectal foreign bodies, whose size and shape are variable and sometimes aberrant, are often self-inserted for self-gratification by adults, and its incidence is increasing. Patients typically avoid immediate medical attention and seek help only when complications arise. Formal clinical guidelines are lacking, and this case illustrates the importance of clinical judgement in the management of rectal foreign bodies, whether endoscopic or surgical.

18.
Rev Esp Enferm Dig ; 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38205710

ABSTRACT

We present the case of a 72-year-old woman admitted for epigastric pain, elevated inflammatory parameters and liver enzymes, with a total bilirubin of 6mg/dL. Abdominal ultrasound identified cholelithiasis and posteriorly endoscopic ultrasound showed a 5.8mm stone distally in the biliary tract. Due to acute cholangitis, she underwent endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy, successfully removing the stone. Mild self-limited bleeding after sphincterotomy was reported, for which an adrenaline flush of the biliary tract was performed. The following day, she presented melena and hemoglobin dropped 3g/dL, remaining hemodynamically stable. With side-viewing duodenoscopy we identified an adherent clot and an oozing bleed near the pancreatic duct opening. The clot was removed with a snare after adrenalin injection and 3 endoclips of 8mm were positioned in the superior portion of the sphincterotomy. Even then, bleeding persisted. We opted to apply hemostatic powder (Hemospray®) with successful bleeding cessation. Four days later the patient was released without bleeding recurrence or suspected biliary blockage.

19.
Rev Esp Enferm Dig ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832594

ABSTRACT

Endoscopic full-thickness resection (eFTR) is an emerging technique that enables effective and safe management of complex colorectal lesions. The full-thickness resection device (FTRD®, Ovesco, Germany) has primarily been used for non-exposed transmural resection of challenging subepithelial or epithelial lesions, where conventional methods may be limited. This technique represents an alternative to surgery in selected patients, and its applications are rapidly expanding. In recent years, eFTR has been described as an alternative to surgery for scars aiming to exclude residual tumors after non-curative endoscopic resection. We present a case of a 41-year-old woman with Lynch syndrome (dMLH1) with rectal adenocarcinoma at the age of 20 underwent anterior resection of the rectum and adjuvant chemoradiotherapy. At the age of 39, during endoscopic surveillance, she presented with a suspicious lesion (Paris 0-Is+IIa, NICE2, JNET2B) measuring 16mm in the hepatic angle, and underwent en bloc endoscopic mucosal resection (EMR). Histopathological analysis revealed a low-grade invasive adenocarcinoma with lymphoid stroma with deep invasion of the submucosa and resection margin involvement (vertical R1). After a multidisciplinary team discussion, complementary surgery was proposed but the patient refused, opting for close endoscopic and imaging surveillance. Two subsequent colonoscopies plus computed tomography (CT) scans showed no signs of macro or microscopic residual or recurrent tumor, even after extensive biopsies of the colonic scar. However, a CT scan 20months post-resection showed a de novo 2cm thickening of the parietal wall in the hepatic angle, consistent with the location of the previous endoscopic resection. Suspecting deep parietal tumor recurrence without superficial endoscopic findings, a transmural endoscopic resection using FTRD® of the EMR scar was performed, whose histology revealed no transparietal tumor recurrence.

20.
J Food Sci Technol ; 61(8): 1547-1556, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38966795

ABSTRACT

Ora-pro-nobis (OPN) is an unconventional food plant with high nutritional value, and its nutritional composition can be altered according to cultivation. Cereal bars are a popular nutrient-poor foods, and OPN could be incorporated to improve the nutritional quality. This study aimed to evaluate the physicochemical characteristics and sensory acceptability of cereal bars enriched with OPN flour (OpnF) from different forms of cultivation. OpnF was obtained by dehydrating and grinding OPN leaves collected in rural (ROpnF) and urban (UOpnF) municipalities. Two formulations of cereal bars, peanut flavor (Bpn) and mango flavor (Bmg), each with 10% OpnF, were prepared. The macronutrients and mineral composition, oxalate content, water activity, texture, color profile, and acceptability were evaluated. ROpnF had the highest protein, iron, and manganese content, whereas UOpnF had the highest ash and magnesium content. The oxalic acid/calcium ratio was 1.43 and did not imply calcium bioavailability. In addition to nutritional and protein values, Bpn and Bmg presented a good sensory acceptability index of > 77.5% with market potential. Bmg has the highest mineral content and is a source of iron, manganese, and magnesium. OpnF can be used in cereal bars and potentially improve nutritional attributes and used in other foods in a similar way.

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