Time-Dependent Effective Hamiltonians for Light-Matter Interactions.

In this paper, we present a systematic approach to building useful time-dependent effective Hamiltonians in molecular quantum electrodynamics. The method is based on considering part of the system as an open quantum system and choosing a convenient unitary transformation based on the evolution operator. We illustrate our formalism by obtaining four Hamiltonians, each suitable to a different class of applications. We show that we may treat several effects of molecular quantum electrodynamics with a direct first-order perturbation theory. In addition, our effective Hamiltonians shed light on interesting physical aspects that are not explicit when employing more standard approaches. As applications, we discuss three examples: two-photon spontaneous emission, resonance energy transfer, and dispersion interactions.

Is endoscopic technique an effective and safe alternative for lumbar interbody fusion? A systematic review and meta-analysis.

Study design: Systematic review; meta-analysis. Purpose: Lumbar degenerative disease is frequent and has a tremendous impact on patients' disability and quality-of-life. Open and minimally invasive procedures have been used to achieve adequate decompression and fusion. Endoscopic lumbar interbody fusion (Endo-LIF) is emerging as an alternative, trying to reduce morbidity, while achieving comparable to superior clinical outcomes. The aim of this work is to perform a systematic review and meta-analysis to investigate how Endo-LIF compares to open or minimally invasive procedures. Methods: Electronic databases (MEDLINE, Scopus, Web of Science, Cochrane) were systematically reviewed using the query: '(percutaneous OR endoscop*) AND (open OR minimal* invasive) AND lumbar AND fusion'. PRISMA guidelines were followed. Results: Twenty-seven articles were included (25 cohort study, 1 quasi-experimental study, and 1 randomized control trial; for meta-analytical results, only observational studies were considered). Endo-LIF conditioned longer operative time, with significantly lower blood loss, bedtime, and hospital length of stay. Early post-operative back pain favored endoscopic techniques. Endo-LIF and non-Endo-LIF minimally invasive surgery displayed comparable results for most back and leg pain or disability outcomes, despite Endo-LIF having been associated with higher disability at late follow-up (versus Open-LIF). No differences were found regarding fusion rates, cage subsidence, or adverse events. Definitive conclusions regarding fusion rate cannot be drawn due to low number of studies and unstandardized fusion definition. Conclusion: Endo-LIF is an effective and safe alternative to conventional lumbar interbody fusion procedures. Evidence shortcomings may be addressed, and future randomized control trials may be performed to compare techniques and to validate results.

Periparturient Changes in Voluntary Intake, Digestibility, and Performance of Grazing Zebu Beef Cows with or without Protein Supplementation.

We aimed to understand the changes in nutritional parameters and performance of beef cows during the peripartum, whether receiving or not receiving protein supplements. Forty cows were used, divided into two treatments: CON-mineral mix and SUP-protein supplementation. Digestibility trial was performed at 45, 30, and 15 days (d) before the parturition and at 20 and 40 d of lactation. The ADG of cows pre- and postpartum was recorded along with the BCS in gestational (GT) and maternal (MT) tissues in the prepartum. There was an effect of treatment and period (p ≤ 0.044) for intakes of DM and CP. The forage intake was similar (p > 0.90) but varied with the effect of days related to parturition (p < 0.001). There was a 14.37% decrease in DM intake from d -30 to d -15 of prepartum. In the postpartum, at 20 d of lactation, there was an increase of 72.7% in relation to d -15 of prepartum. No differences were observed in postpartum ADG or BCS at parturition and postpartum (p ≥ 0.12). However, higher total and MT ADG (p ≤ 0.02) were observed in animals receiving supplementation, while ADG in GT remained similar (p > 0.14). In conclusion, there is a decrease in intake for pregnant cows close to parturition and greater performance of animals supplemented in prepartum.

Subclinical spinal muscular atrophy in a 60-year-old man.

Spinal muscular atrophy is an autosomal recessive genetic disease that can manifest with different phenotypes, classified as types 1 to 4, being type 4 the mildest form. We report a case of a 60-year-old man presenting with sudden onset of numbness in the right upper limb and with a family history of a 48-year-old brother with progressive weakness. At the first visit, his exam was unremarkable, except for a mild paresis of the right elbow extension and reduced right bicipital and tricipital reflexes. Electromyography revealed chronic motor neuronopathy and the genetic study confirmed a diagnosis of spinal muscular atrophy. At the follow-up visit his complains improved and his neurologic exam returned to normal. To our knowledge, this patient is the oldest asymptomatic SMA individual ever reported. This case highlights the need to exclude late onset spinal muscular atrophy in patients with indolent motor neuronopathy.

Comparison of Multiparametric MRI and the Combination of PSMA Plus MRI for the Intraprostatic Diagnosis of Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this study was to perform a head-to-head comparison of multiparametric MRI (mpMRI) and the combination of prostate-specific membrane antigen (PSMA) PET plus MRI (PSMA + MRI) for detecting intraprostatic clinically significant prostate cancer (csPCa). PATIENTS AND METHODS: Relevant databases were searched through November 2023. Only studies directly comparing mpMRI and PSMA + MRI (PET/MRI or PET/CT + mpMRI) were included. A meta-analysis with a random-effects model was used to estimate pooled sensitivity, specificity, and area under the curve for each approach. RESULTS: A total of 19 studies were included. On a patient-level analysis, PSMA + MRI had higher sensitivity (9 studies) than mpMRI for csPCa detection (96% [95% confidence interval (CI): 92%, 98%] vs 89% [95% CI: 81%, 94%]; P = 0.04). The patient-level specificity (4 studies) of PSMA + MRI was 55% (95% CI: 31%-76%) compared with 50% (95% CI: 44%-57%) of mpMRI ( P = 0.67). Region-level sensitivity (10 studies) was 85% (95% CI: 74%-92%) for PSMA + MRI and 71% (95% CI: 58%-82%) for mpMRI ( P = 0.09), whereas specificity (4 studies) was 87% (95% CI: 76%-94%) and 90% (95% CI: 82%-95%), respectively ( P = 0.59). Lesion-level sensitivity and specificity were similar between modalities with pooled data from less than 4 studies. CONCLUSIONS: PSMA + MRI had superior pooled sensitivity and similar specificity for the detection of csPCa compared with mpMRI in this meta-analysis of head-to-head studies.

Lateral rectus pulley concerning the orbital wall. Area of a stereotyped bony insertion.

Purpose: To examine the lateral rectus muscle pulley and its bony insertion concerning the orbital rim and periorbita. Design: Prospective. An observational anatomic study. Methods: Study population: Twenty postmortem orbits (10 right, 10 left) of 10 Caucasian cadavers (8 females, 2 males; age range at death, 57-100 years; median age, 79.5 years) fixed by the Thiel method.Intervention: The floor of the temporal fossa was exposed, and a bone window on the lateral wall of the orbit, posterior to the sphenozygomatic suture, was created, keeping the periorbita intact. The lateral canthus and lateral palpebral ligament were isolated and opened, and the eyelids were folded back. The frontozygomatic suture was identified, and the orbital septum opened adjacent to the orbital rim. The conjunctiva was opened at the limbus, and the lateral rectus insertion was isolated. The bone pillar containing the frontozygomatic suture and the insertion of the periorbita and the pulley was isolated and removed en bloc. The lateral rectus muscle was isolated and excised.Main outcome measures: Position of the pulley ring on the lateral rectus muscle belly and its bony attachment area in the lateral wall of the orbit. Results: The pulley bony attachment was roughly quadrilateral with an approximate area of 90 mm2, 3 mm (mean, range 1-5 mm) posteroinferior to the frontozygomatic suture and 1 mm posterior to the orbital rim. The anterior margin of the pulley sleeve was found at 21.0 mm (median, p25-75 20.0-22.8) from the scleral insertion. Conclusions: The lateral rectus pulley is stereotyped in its position in the muscle belly and its bony insertion, coinciding with the point of greatest adhesion of the periorbita to the anterior part of the lateral wall of the orbit.

Rare origin of the sinoatrial node artery: an anatomic report and a brief review of the literature.

Several studies reported anatomical variations in the sinoatrial node artery (SANa). Here, we report a rare variation in the origin of the SANa on a human adult male cadaver. During dissection, we identified the SANa originating from a large atrial branch of the right coronary artery (RCA). This branch originates at the level of the inferior border of the heart and courses upwards. The initial part of this vessel is tortuous, and then it follows a straight path parallel to the RCA along the anterior surface of the right atrium. After this part, the artery curves posteriorly and to the left until it reaches the lower border of the right auricle, where it closely approaches the RCA. Finally, the artery runs posteriorly and to the right to follow a course along the medial wall of the right auricle and right atrium to reach a location close to the region of the junction of the superior vena cava and right atrium, where it follows its path buried in the myocardium. After perforating the myocardium, this vessel gives rise to branches that are distributed to both atria in addition to the SANa. The SANa runs to the sinoatrial node in a precaval (anterior to the superior vena cava) course. We also tried to characterize the vessels radiologically. The knowledge of the anatomical variations of the SANa is of the utmost importance for cardiologists and heart surgeons to better understand cardiac disease and accurately plan and execute cardiac interventions and surgical procedures.

Prosthetic Joint Infections Caused by Mycobacterium tuberculosis Complex-An ESGIAI-ESGMYC Multicenter, Retrospective Study and Literature Review.

PURPOSE: While tuberculosis remains a significant global health concern, prosthetic joint infections (PJIs) caused by members of the Mycobacterium tuberculosis complex are exceptionally rare. Our objective is to perform a retrospective search of new cases of this disease and analyze all cases available in the literature of tuberculous PJIs, aiming to detect factors that may influence patient outcomes. METHODS: The ESGIAI and ESGMYC study groups were used to collect information on non-published cases of tuberculous prosthetic joint infections (PJIs). Additionally, a literature review of all published cases of tuberculous PJIs was conducted. All identified cases in the retrospective study and in the literature review were merged and included in the statistical analysis, involving both univariate and multivariate analyses. RESULTS: Fifteen previously unreported cases of tuberculous prosthetic joint infections (PJIs) from four countries were detailed. Among them, ten patients were female, with a median age of 76 years. The hip was affected in 13 cases. Seven patients experienced co-infection with another microorganism. Treatment approaches varied, with 13 patients undergoing implant removal, one treated with DAIR (debridement, antibiotics, and implant retention), and one case was treated with an unknown treatment method. All patients received antibiotic therapy and achieved a cure. The literature review that was conducted detected 155 published cases. Univariate analysis revealed a statistical significance for previous tuberculosis, joint, and no importance of surgery for cure. CONCLUSIONS: Tuberculous prosthetic joint infection (PJI) is a rare condition, typically presenting as a localized chronic infection. Antibiotic treatment is essential for the management of these patients, but neither surgical treatment nor duration of treatment seems to have importance in the outcome.

High-Caloric Diets in Adolescence Impair Specific GABAergic Subpopulations, Neurogenesis, and Alter Astrocyte Morphology.

We compared the effects of two different high-caloric diets administered to 4-week-old rats for 12 weeks: a diet rich in sugar (30% sucrose) and a cafeteria diet rich in sugar and high-fat foods. We focused on the hippocampus, particularly on the gamma-aminobutyric acid (GABA)ergic system, including the Ca2+-binding proteins parvalbumin (PV), calretinin (CR), calbindin (CB), and the neuropeptides somatostatin (SST) and neuropeptide Y (NPY). We also analyzed the density of cholinergic varicosities, brain-derived neurotrophic factor (BDNF), reelin (RELN), and cyclin-dependent kinase-5 (CDK-5) mRNA levels, and glial fibrillary acidic protein (GFAP) expression. The cafeteria diet reduced PV-positive neurons in the granular layer, hilus, and CA1, as well as NPY-positive neurons in the hilus, without altering other GABAergic populations or overall GABA levels. The high-sugar diet induced a decrease in the number of PV-positive cells in CA3 and an increase in CB-positive cells in the hilus and CA1. No alterations were observed in the cholinergic varicosities. The cafeteria diet also reduced the relative mRNA expression of RELN without significant changes in BDNF and CDK5 levels. The cafeteria diet increased the number but reduced the length of the astrocyte processes. These data highlight the significance of determining the mechanisms mediating the observed effects of these diets and imply that the cognitive impairments previously found might be related to both the neuroinflammation process and the reduction in PV, NPY, and RELN expression in the hippocampal formation.

Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country.

BACKGROUND: The Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. METHODS: Retrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). RESULTS: We evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. CONCLUSION: We found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.

Low-lying Negative Ion States Probed in Potassium - Ethanol Collisions.

Dissociative electron transfer in collisions between neutral potassium atoms and neutral ethanol molecules yields mainly OH-, followed by C2H5O-, O-, CH3 - and CH2 -. The dynamics of negative ions have been investigated by recording time-of-flight mass spectra in a wide range of collision energies from 17.5 to 350 eV in the lab frame, where the branching ratios show a relevant energy dependence for low/intermediate collision energies. The dominant fragmentation channel in the whole energy range investigated has been assigned to the hydroxyl anion in contrast to oxygen anion from dissociative electron attachment (DEA) experiments. This result shows the relevant role of the electron donor in the vicinity of the temporary negative ion formed allowing access to reactions which are not thermodynamically attained in DEA experiments. The electronic state spectroscopy of such negative ions, was obtained from potassium cation energy loss spectra in the forward scattering direction at 205 eV impact energy, showing a prevalent Feshbach resonance at 9.36±0.10 eV with σ O H * / σ C H * ${{\sigma }_{OH}^{^{\ast}}/{\sigma }_{CH}^{^{\ast}}}$ character, while a less pronounced σ O H * ${{\sigma }_{OH}^{^{\ast}}}$ contribution assigned to a shape resonance has been obtained at 3.16±0.10 eV. Quantum chemical calculations for the lowest-lying unoccupied molecular orbitals in the presence of a potassium atom have been performed to support the experimental findings.

Gut Microbiome Changes in Patients With Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: The gut microbiome is a complex system within the human gastrointestinal tract. The bacteria play a significant role in human health, and some can promote inflammation and pathologic processes through chemical interactions or metabolites. Gut microbiome dysbiosis has been linked to some neurological and other diseases. Here we aimed to examine microbiome differences between patients with a progressive neurological disorder, idiopathic normal pressure hydrocephalus (iNPH), compared with healthy controls (CO). METHODS: We recruited 37 neurologically healthy CO and 10 patients with shunted iNPH. We evaluated these participants' cognition using the CERAD-NB test battery and CDR test, and collected a variety of information, including about dietary habits and health. We also collected fecal samples, which were subjected to 16S amplicon sequencing to analyze differences in gut microbiome composition. RESULTS: We found that the iNPH group exhibited significantly different abundances of 10 bacterial genera compared with the CO group. The Escherichia/Shigella and Anaeromassilibacillus genera were most remarkably increased. Other increased genera were Butyrivibrio , Duncaniella , and an unidentified genus. The decreased genera were Agathobaculum , Paramuribaculum , Catenibacterium , and 2 unidentified genera. CONCLUSIONS: Here we report the first identified microbiome differences in iNPH patients compared with healthy controls.

Bladder duplication in a patient with a persistent urogenital sinus: Case report and systematic review of the literature.

Bladder duplication (BD) is a rare malformation that is often associated to other anomalies. We report a newborn diagnosed with BD in the sagittal plane, associated to persistent urogenital sinus (UGS), given the opening of the vagina immediately below the bladder neck. It is the fourth time this association is reported. Surgical repair was made: both bladders were joined, the common channel was left as urethra and the vagina was descended with a vaginoplasty with an intestinal segment. She also presented an anterior anus, that required posterior mobilization. The patient is currently 3 years old with good sphincter control.

Sinonasal Adenocarcinoma: Clinicopathological Characterization and Prognostic Factors.

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

Long-term outcome of pediatric renal transplantation with donors younger than 6 years.

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.

Development of supramolecular anticoagulants with on-demand reversibility.

Drugs are administered at a dosing schedule set by their therapeutic index, and termination of action is achieved by clearance and metabolism of the drug. In some cases, such as anticoagulant drugs or immunotherapeutics, it is important to be able to quickly reverse the drug's action. Here, we report a general strategy to achieve on-demand reversibility by designing a supramolecular drug (a noncovalent assembly of two cooperatively interacting drug fragments held together by transient hybridization of peptide nucleic acid (PNA)) that can be reversed with a PNA antidote that outcompetes the hybridization between the fragments. We demonstrate the approach with thrombin-inhibiting anticoagulants, creating very potent and reversible bivalent direct thrombin inhibitors (Ki = 74 pM). The supramolecular inhibitor effectively inhibited thrombus formation in mice in a needle injury thrombosis model, and this activity could be reversed by administration of the PNA antidote. This design is applicable to therapeutic targets where two binding sites can be identified.

EGFR signaling and pharmacology in oncology revealed with innovative BRET-based biosensors.

Mutations of receptor tyrosine kinases (RTKs) are associated with the development of many cancers by modifying receptor signaling and contributing to drug resistance in clinical settings. We present enhanced bystander bioluminescence resonance energy transfer-based biosensors providing new insights into RTK biology and pharmacology critical for the development of more effective RTK-targeting drugs. Distinct SH2-specific effector biosensors allow for real-time and spatiotemporal monitoring of signal transduction pathways engaged upon RTK activation. Using EGFR as a model, we demonstrate the capacity of these biosensors to differentiate unique signaling signatures, with EGF and Epiregulin ligands displaying differences in efficacy, potency, and responses within different cellular compartments. We further demonstrate that EGFR single point mutations found in Glioblastoma or non-small cell lung cancer, impact the constitutive activity of EGFR and response to tyrosine kinase inhibitor. The BRET-based biosensors are compatible with microscopy, and more importantly characterize the next generation of therapeutics directed against RTKs.

Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy.

INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.

Proteomic Profiling of Plasma- and Gut-Derived Extracellular Vesicles in Obesity.

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.

Two-devices-in-one-channel method: a challenging cannulation of intradiverticular major papilla.

Video 1Two-devices-in-one-channel method with a SpyGlass retrieval basket (Boston Scientific, Marlborough, Mass, USA) grabbing and pulling one of the previously placed through-the-scope clips and biliary cannulation with a conventional sphincterotome, using the double-guidewire technique.