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1.
Small ; : e2404268, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011945

RESUMEN

Active control of nanotribological properties is a challenge. Materials responsive to external stimuli may catalyze this paradigm shift. Recently, the nanofriction of a thin film is modulated by light, ushering in phototribology. This frontier is expanded here, by investigating photoactive nanoparticles in lubricants to confer similar functionality to passive surfaces. Quartz-crystal microbalance (QCM) is employed to assess the phototribological behavior of aqueous suspensions of titanium dioxide nanoparticles. A comparison of dark and illuminated conditions provides the first demonstration of tuning the interfacial friction in solid-nanosuspension interfaces by light. Cyclic tests reveal reversible transitions between higher (dark) and lower friction (illuminated) regimes. These transitions are underpinned by transient states with surface charge variations, as confirmed by Zeta potential measurements. The accumulated surface charge increases repulsion within the system and favors sliding. Upon cessation of illumination, the system returns to its prior equilibrium state. These findings impact not only nanotribology but nanofluidics and nanorheology. Furthermore, the results underscore the need to consider light-induced effects in other scenarios, including the calculation of activity coefficients of photoactive suspensions. This multifaceted study introduces a new dimension to in operando frictional tuning, beckoning a myriad of applications and fundamental insights at the nanoscale.

2.
Liver Transpl ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38949782

RESUMEN

INTRODUCTION: Advances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference. We aimed to compare three different protocols from four different centers to identify differences in outcomes after one year of follow-up. MATERIALS AND METHODS: A retrospective analysis of the databases of the participating centers was performed. Consecutive patients aged <18 years with a first liver-only transplant and no other underlying congenital or acquired immunodeficiency were included. Patients were classified according to the immunosuppression protocol as follows: Group A (Prednisone + Tacrolimus + Basiliximab), Group B (Prednisone + Tacrolimus + Basiliximab + anti-thymocyte globulin), and Group C (Prednisone + Tacrolimus). Differences in survival, frequency of rejection, infections, and other complications were analyzed in the entire group (n=97) and in the group with biliary atresia (n=48). RESULTS: After one year of follow-up, no differences in patient or graft survival were observed when comparing either the entire group (n=97) or patients with biliary atresia only (n=48). The frequencies of rejection and episodes of infection were similar. Renal function showed no differences either before or after transplantation or between the groups. CONCLUSION: Immunosuppression protocols used in this study appeared to be equally safe and effective. This could offer the opportunity to tailor them to the patient's individual characteristics without compromising the outcome.

3.
Clin Endocrinol (Oxf) ; 100(5): 468-476, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38472743

RESUMEN

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Humanos , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Tiroidectomía , Guías de Práctica Clínica como Asunto
4.
J Neuroophthalmol ; 44(1): 22-29, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38251954

RESUMEN

BACKGROUND: MRI abnormalities are common in optic neuropathies, especially on dedicated orbital imaging. In acute optic neuritis, optic nerve T2-hyperintensity associated with optic nerve contrast enhancement is the typical imaging finding. In chronic optic neuropathies, optic nerve T2-hyperintensity and atrophy are regularly seen. Isolated optic nerve T2-hyperintensity is often erroneously presumed to reflect optic neuritis, frequently prompting unnecessary investigations and neuro-ophthalmology consultations. Our goal was to determine the significance of optic nerve/chiasm T2-hyperintensity and/or atrophy on MRI. METHODS: Retrospective study of consecutive patients who underwent brain/orbital MRI with/without contrast at our institution between July 1, 2019, and June 6, 2022. Patients with optic nerve/chiasm T2-hyperintensity and/or atrophy were included. Medical records were reviewed to determine the etiology of the T2-hyperintensity and/or atrophy. RESULTS: Four hundred seventy-seven patients (698 eyes) were included [mean age 52 years (SD ±18 years); 57% women]. Of the 364 of 698 eyes with optic nerve/chiasm T2-hyperintensity without atrophy, the causes were compressive (104), inflammatory (103), multifactorial (49), glaucoma (21), normal (19), and other (68); of the 219 of 698 eyes with optic nerve/chiasm T2-hyperintensity and atrophy, the causes were compressive (57), multifactorial (40), inflammatory (38), glaucoma (33), normal (7), and other (44); of the 115 of 698 eyes with optic nerve/chiasm atrophy without T2-hyperintensity, the causes were glaucoma (34), multifactorial (21), inflammatory (13), compressive (11), normal (10), and other (26). Thirty-six eyes with optic nerve/chiasm T2-hyperintensity or atrophy did not have evidence of optic neuropathy or retinopathy on ophthalmologic examination, and 17 eyes had clinical evidence of severe retinopathy without primary optic neuropathy. CONCLUSIONS: Optic nerve T2-hyperintensity or atrophy can be found with any cause of optic neuropathy and with severe chronic retinopathy. These MRI findings should not automatically prompt optic neuritis diagnosis, workup, and treatment, and caution is advised regarding their use in the diagnostic criteria for multiple sclerosis. Cases of incidentally found MRI optic nerve T2-hyperintensity and/or atrophy without a known underlying optic neuropathy or severe retinopathy are rare. Such patients should receive an ophthalmologic examination before further investigations.


Asunto(s)
Glaucoma , Atrofia Óptica , Enfermedades del Nervio Óptico , Traumatismos del Nervio Óptico , Neuritis Óptica , Enfermedades de la Retina , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Enfermedades del Nervio Óptico/patología , Neuritis Óptica/etiología , Imagen por Resonancia Magnética/métodos , Atrofia Óptica/diagnóstico , Atrofia Óptica/complicaciones , Traumatismos del Nervio Óptico/complicaciones , Atrofia/complicaciones , Atrofia/patología , Glaucoma/complicaciones , Glaucoma/patología , Enfermedades de la Retina/complicaciones
5.
Sensors (Basel) ; 24(5)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38474910

RESUMEN

Today, online partial discharge (PD) measurements are common practice to assess the condition status of dielectrics in high-voltage (HV) electrical grids. However, when online PD measurements are carried out in electrical facilities, several disadvantages must be considered. Among the most important are high levels of changing electrical noise and interferences, signal phase couplings (cross-talk phenomena), and the simultaneous presence of various defects and difficulties in localizing and identifying them. In the last few decades, various PD-measuring systems have been developed to deal with these inconveniences and try to achieve the adequate supervision of electrical installations. In the state of the art, one of the main problems that electrical companies and technology developers face is the difficulty in characterizing the measuring system's functionalities in laboratory setups or in real-world facilities, where simulated or real defects must be detected. This is mainly due to the complexity and costs that the laboratory setups entail and the fact that the facilities are permanently in service. Furthermore, in the latter scenario, owners cannot assign facilities to carry out the tests, which could cause irreversible damage. Additionally, with the aforementioned installations, a comparison of results over time in various locations is not possible, and noise conditions cannot be controlled to perform the characterizations in a correct way. To deal with the problems indicated, in this article, an affordable scale modular test platform that simulates an HV installation is presented, where real on-site PD measuring conditions are simulated and controlled. In this first development, the HV installation comprises a cable system connected at both ends to a gas-insulated substation (GIS). As the most common acquisition technique in online applications is based on the placement of high-frequency current transformer (HFCT) sensors in the grounding cables of facilities, the test platform is mainly adapted to carry out measurements with this type of sensor. The designed and developed test platform was validated to assess its features and the degree of convergence with a real installation, showing the convenience of its use for the appropriate and standardized characterization of PD-measuring systems.

6.
Sensors (Basel) ; 24(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38931571

RESUMEN

During their lifespan, high-voltage (HV) electrical systems are subjected to operating conditions in which electrical, mechanical, thermal and environmental-related stresses occur. These conditions over time lead to unforeseen failures caused by various types of defects. For this reason, there are several technologies for measuring and monitoring the electrical systems, with the aim of minimizing the number of faults. The early detection of defects, preferably in their incipient state, will enable the necessary corrective actions to be taken in order to avoid unforeseen failures. These failures generally lead to human risks and material damage, lack of power supply and significant economic losses. An efficient maintenance technique for the early detection of defects consists of the supervision of the dielectrics status in the installations by means of on-line partial discharge (PD) measurement. Nowadays, there are numerous systems in the market for the measurement of PD in HV installations. The most efficient with a reasonable cost will be those that offer greater security guarantees and the best positioned in the market. Currently, technology developers and users of PD measuring systems face difficulties related to the lack of reference procedures for their complete characterization and to the technical and economic drawback of performing the characterization tests on site or in laboratory installations. To deal with the previous difficulties, in this paper a novel method for the complete and standardized characterization of PD measuring systems is presented. The applicability of this method is mainly adapted for the characterization of systems operating in on-line applications using high-frequency current transformer (HFCT) sensors. For the appropriate application of the method, an associated and necessary scale modular test platform is used. In the test platform, the real on-site measuring conditions of an HV insulated distribution line are simulated in a controlled way. Practical characterizations, showing the convenience and advantages of applying the method using the modular test platform, are also presented.

7.
Rev Esp Enferm Dig ; 116(7): 363-368, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38835233

RESUMEN

The Asociación Española de Pancreatología (AESPANC), Asociación Española de Gastroenterología (AEG), and Sociedad Española de Patología Digestiva (SEPD) have developed a consensus document on the standards and recommendations they consider essential for the organization of pancreas units (PUs) within gastroenterology services (GSs) in order to conduct their activities in an efficient, high-quality manner. The consensus document defines PUs and lays down standards relating to their organization, structure, service portfolio, processes, and teaching and research activities. Standards have been categorized as mandatory (requirements to be met to qualify for certification by the scientific societies responsible for the standards) or recommendations. Standards should be updated at most within five years based on the experience gained in Spanish PUs and the advance of knowledge regarding pancreas disease. Development of health outcome indicators, including patient-reported outcome measures (PROMs), is considered a relevant challenge, as is evidence on the association of PU structure and activity standards with health outcomes.


Asunto(s)
Gastroenterología , Atención Dirigida al Paciente , Humanos , Gastroenterología/normas , Gastroenterología/organización & administración , Atención Dirigida al Paciente/normas , Atención Dirigida al Paciente/organización & administración , Enfermedades Pancreáticas/terapia , España
8.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38862300

RESUMEN

The Asociación Española de Pancreatología (AESPANC), Asociación Española de Gastroenterología (AEG), and Sociedad Española de Patología Digestiva (SEPD) have developed a consensus document on the standards and recommendations they consider essential for the organization of pancreas units (PUs) within gastroenterology services (GSs) in order to conduct their activities in an efficient, high-quality manner. The consensus document defines PUs and lays down standards relating to their organization, structure, service portfolio, processes, and teaching and research activities. Standards have been categorized as mandatory (requirements to be met to qualify for certification by the scientific societies responsible for the standards) or recommendations. Standards should be updated at most within five years based on the experience gained in Spanish PUs and the advance of knowledge regarding pancreas disease. Development of health outcome indicators, including patient-reported outcome measures (PROMs), is considered a relevant challenge, as is evidence on the association of PU structure and activity standards with health outcomes.

9.
Can Liver J ; 7(1): 64-69, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38505788

RESUMEN

Background: Pediatric acute liver failure (PALF) is a potentially lethal and rapidly progressive clinical syndrome, with a large proportion of cases remaining indeterminate despite extensive investigations. Patients and Results: In this case report, we describe two male children with indeterminate PALF and a family history of autoimmune disease, both of whom were lymphopenic with necrosis, inflammation, and lymphocytic infiltrates on their liver biopsies. One of these patients subsequently developed hepatitis-associated aplastic anemia. Notably, in addition to receiving standard liver failure care, both patients were successfully treated off-label with anti-thymocyte globulin (ATG), as well as a more prolonged course of cyclosporine and corticosteroids. Conclusions: The fact that these medications all suppress T lymphocytes further supports the theory that T-cell activation plays a prominent role in the pathophysiology of indeterminate hepatitis. Further research should examine the short-term and long-term effects of ATG in this population, as well as the necessary duration of treatment with immune-suppressing agents.

10.
Arch Argent Pediatr ; : e202410380, 2024 Jul 25.
Artículo en Inglés, Español | MEDLINE | ID: mdl-39024502

RESUMEN

Advances in molecular biology achieved during the last years have allowed us to know the genes involved in biliary secretion and the mutations capable of generating cholestasis. The mechanisms involved in forming bile and its circulation have been clarified. According to the biology of biliary secretion, we classify the genetic causes of cholestasis as follows: 1) transport abnormalities in canalicular or basolateral membranes, 2) alterations in intracellular vesicle transit, 3) increased paracellular permeability, 4) mutations in nuclear receptors, 5) cholangiopathies, and 6) hepatocellular diseases, due to disturbance of the function of intracellular organelles or errors of metabolism. This physiopathological classification of chronic cholestasis in childhood will facilitate pediatricians' diagnostic guidance and timely specialized referrals, as patients should receive early and appropriate treatment for its complications.


Los avances en biología molecular alcanzados durante los últimos años nos han permitido conocer los genes que intervienen en la secreción biliar y las mutaciones capaces de generar un cuadro de colestasis. Los mecanismos involucrados en la formación de la bilis y su circulación han sido precisados. De acuerdo a la biología de la secreción biliar, clasificamos las causas genéticas de colestasis en 1) anomalías del transporte en las membranas canalicular o basolateral, 2) alteraciones del tránsito de vesículas intracelulares, 3) aumento de la permeabilidad paracelular, 4) mutaciones en los receptores nucleares, 5) colangiopatías, 6) enfermedades hepatocelulares, por perturbación de la función de orgánulos intracelulares o errores del metabolismo. Esta clasificación fisiopatológica de las colestasis crónicas de la infancia facilitará la orientación diagnóstica de los pediatras y la derivación especializada oportuna, ya que los pacientes deben recibir tempranamente un tratamiento adecuado a las complicaciones de la colestasis.

11.
JPGN Rep ; 5(3): 326-333, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39149184

RESUMEN

Objectives: Pediatric autoimmune hepatitis has an incidence of 0.23/100.000 children in North America, with a bleak prognosis if left untreated. Steroids are the therapy of choice but are not always effective. B cell depletion is a safe and effective therapy that allows for a steroid-sparing protocol, especially in patients who do not tolerate side effects. Methods: We retrospectively reviewed rituximab-treated patients between 2017 and 2022. Demographics, previous treatments, reasons for B cell depletion, response, and adverse effects were noted. Results: Six patients with a mean age of 10.2 years were included. All patients had comorbidities that rendered treatment with steroids unsuccessful or undesirable. Rituximab was started at a mean follow-up of 8 months. After 6 months, the mean alanine transaminase and aspartate transaminase levels decreased from 575 IU/L and 342 IU/L, respectively, to 28 IU/L (p = 0.02) and 36 IU/L (p = 0.008), respectively. Mean γ-glutamyl transpeptidase decreased from 105 to 25 IU/L (p = 0.01). Immunoglobulin G levels were normalized in all patients (p = 0.01). No severe adverse events were observed. One patient had persistent hypogammaglobulinemia, and another had lymphopenia. Conclusion: B-cell depletion is an effective and safe treatment for autoimmune liver diseases and should be included as an option, particularly for relapsing patients in whom steroids are undesirable or have shown nonadherence.

12.
Arch Argent Pediatr ; 122(5): e202310246, 2024 10 01.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38656883

RESUMEN

Gallbladder agenesis is a rare condition in pediatrics that is usually asymptomatic and represents a diagnostic challenge for physicians seeing these cases for the first time. Some patients may, however, present with symptoms that mimic other diseases of the bile ducts, and many of them undergo surgery due to such suspicion. Still, a timely diagnosis of gallbladder agenesis allows for medical treatment that is often sufficient to resolve the patient's problem. Although it is a benign condition, patients often present with other associated, more serious malformations and should be actively studied for a timely referral to other specialists. Here we describe our experience with the diagnosis and treatment of these patients and a brief review of the bibliography. We hope it will be helpful for physicians facing similar cases.


La agenesia de la vesícula biliar es una entidad rara en pediatría con una evolución normalmente silente, y representa un desafío diagnóstico para el médico que enfrenta estos casos por primera vez. Algunos pacientes pueden, sin embargo, presentar síntomas que simulan otras patologías del árbol biliar, y muchos de ellos son operados ante esta sospecha. Sin embargo, el diagnóstico oportuno de esta entidad permite llevar a cabo un tratamiento médico que muchas veces es suficiente para resolver el problema del paciente. Si bien es una condición benigna, los pacientes suelen presentar otras malformaciones asociadas que son más graves en naturaleza y que deben investigarse activamente para poder derivarlos a los especialistas de manera oportuna. Presentamos nuestra experiencia en el diagnóstico y tratamiento de estos pacientes, así como una breve revisión de la literatura. Esperamos que sea de utilidad para el médico que encuentre un caso similar.


Asunto(s)
Vesícula Biliar , Humanos , Vesícula Biliar/anomalías , Femenino , Masculino , Niño , Lactante , Preescolar , Adolescente , Anomalías Congénitas
13.
Front Immunol ; 15: 1331846, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38605970

RESUMEN

Foxp3+ TREG cells have been at the focus of intense investigation for their recognized roles in preventing autoimmunity, facilitating tissue recuperation following injury, and orchestrating a tolerance to innocuous non-self-antigens. To perform these critical tasks, TREG cells undergo deep epigenetic, transcriptional, and post-transcriptional changes that allow them to adapt to conditions found in tissues both at steady-state and during inflammation. The path leading TREG cells to express these tissue-specialized phenotypes begins during thymic development, and is further driven by epigenetic and transcriptional modifications following TCR engagement and polarizing signals in the periphery. However, this process is highly regulated and requires TREG cells to adopt strategies to avoid losing their regulatory program altogether. Here, we review the origins of tissue-resident TREG cells, from their thymic and peripheral development to the transcriptional regulators involved in their tissue residency program. In addition, we discuss the distinct signalling pathways that engage the inflammatory adaptation of tissue-resident TREG cells, and how they relate to their ability to recognize tissue and pathogen-derived danger signals.


Asunto(s)
Autoinmunidad , Linfocitos T Reguladores , Factores de Transcripción Forkhead/metabolismo , Timo/metabolismo
14.
EFSA J ; 22(8): e8986, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39175623

RESUMEN

Following a request from the European Commission, the European Food Safety Authority (EFSA) assessed the 2022 post-market environmental monitoring (PMEM) report on the cultivation of Cry1Ab-expressing maize event MON 810. Overall, the 2022 PMEM report provides no evidence of adverse effects of maize MON 810 cultivation. It shows a high level of compliance with refuge requirements by Spanish and Portuguese farmers growing maize MON 810, but uncertainty remains on compliance in areas where the clustered surface of maize MON 810 farms exceeds 5 ha. There are no signs of practical resistance to Cry1Ab in the field in corn borer populations collected in north-eastern Spain in 2022, although a decrease in Cry1Ab susceptibility in Mediterranean corn borer populations from this area cannot be excluded. Information retrieved through farmer questionnaires in Spain and from the scientific literature reveals no unanticipated adverse effects on human and animal health or the environment arising from the cultivation of maize MON 810. Uncertainties remain on whether 'very highly' and 'extremely' sensitive non-target lepidoptera are potentially exposed to harmful amounts of MON 810 pollen. EFSA notes that several recommendations made in the frame of the assessment of previous PMEM reports remain unaddressed and identified additional shortcomings in the 2022 PMEM report that require further consideration by the consent holder in future annual PMEM reports. Particularly, EFSA emphasises the urgent need to increase the sensitivity of the insect resistance monitoring strategy and implement mitigation measures to ensure that the exposure of non-target lepidoptera to maize MON 810 pollen is reduced to levels of no concern.

15.
Front Pediatr ; 12: 1431008, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040669

RESUMEN

Purpose: Renal replacement therapy (RRT) is used in hyperammonemia to reduce the concentration of ammonia in the blood. In the case of plasma hyperosmolarity, RRT can also rapidly decrease plasma osmolarity, which may increase cerebral edema in these patients and favor the occurrence of brain herniation. Methods: We conducted a retrospective clinical study in a tertiary care university-affiliated hospital. All patients admitted in a Pediatric Intensive Care Unit (PICU), less than 18 years old with ammonemia >150 µmol/L and who underwent RRT between January 2015 and June 2023 were included. We collected data on plasma osmolarity levels, osmolar gap and blood ammonia levels before and during RRT. Results: Eleven patients were included (10 with acute liver failure and 1 with a urea cycle disorders). Their mean age was 36.2 months. Before RRT, the median highest measured osmolarity was 320 (305-324) mOsm/L, whereas the median calculated osmolarity was 303 (293-314) mOsm/L, corresponding to an osmolar gap of 14 mOsm/L. Ammonia blood level over 400 µmol/L are significantly associated with higher plasma osmolarity (P-Value <0.001). In one case, a patient had a brain herniation episode after a quick osmolar drop. This episode was reversed by the administration of hyperosmolar agents and the temporary suspension of RRT. Conclusion: This study highlights the hyperosmolarity and high osmolar gap that occur in children with hyperammonemia. A careful monitoring and control of plasma osmolarity evolution may alert clinician on the risk of occurrence of neurological complication such as brain herniation.

16.
Front Immunol ; 15: 1436151, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076982

RESUMEN

Introduction: Exosomes produced by the protozoan parasite Leishmania (LeishEXO) are well-established drivers of virulence, though mechanisms underlying their exacerbation of experimental leishmaniasis remain elusive. Expression of Annexin A1 (ANXA1), a protein implicated in exosome-mediated pathologies and viral internalization, has been shown to correlate with cutaneous leishmaniasis severity. Given ANXA1's regulation of myeloid cells - the canonical hosts for Leishmania - we studied the potential role of ANXA1 and its receptors FPR1/2 in exerting LeishEXO's effects. Methods: Murine and in vitro ANXA1-/- models were used to study the generation of protective TH1 responses during experimental L. major infection with and without LeishEXO. Recruitment of inflammatory cells was assessed using a peritoneal cell recruitment assay and immunophenotyping, and production of inflammatory mediators was measured using a cytokine and chemokine array. Treatment of experimental models with FPR2 antagonist WRW4 and FPR1/2 agonist WKYMVm was used to delineate the role of the FPR/ANXA1 axis in LeishEXO-mediated hyperpathogenesis. Results: We established that ANXA1 deficiency prohibits LeishEXO-mediated pathogenesis and myeloid cell infection, with minimal alterations to adaptive and innate immune phenotypes. FPR2 blockade with WRW4 similarly inhibited leishmanial hyperpathogenesis, while direct activation of FPRs with WKYMVm enhanced infection and recapitulated the LeishEXO-mediated phenotype. This research describes LeishEXO's utilization of the ANXA1/FPR axis to facilitate parasitic internalization and pathogenesis, which may be leveraged in the development of therapeutics for leishmaniasis.


Asunto(s)
Anexina A1 , Exosomas , Leishmania major , Leishmaniasis Cutánea , Ratones Noqueados , Receptores de Formil Péptido , Anexina A1/metabolismo , Anexina A1/genética , Animales , Exosomas/metabolismo , Exosomas/inmunología , Leishmania major/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/metabolismo , Ratones , Receptores de Formil Péptido/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Piel/parasitología , Piel/inmunología , Piel/patología , Piel/metabolismo , Células TH1/inmunología , Femenino
17.
J Neurol ; 271(7): 4237-4248, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38619596

RESUMEN

INTRODUCTION: Recent diagnostic criteria for optic neuritis include T2-hyperintensity of the optic nerve (ON), even without associated contrast enhancement. However, isolated ON-T2-hyperintensity is a nonspecific finding found in any optic neuropathy or severe retinopathy. We applied the 2022 optic neuritis diagnostic criteria to a cohort of patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one eye, to assess the rate of optic neuritis misdiagnosis using these criteria. METHODS: Retrospective study of consecutive patients who underwent brain/orbit MRI with/without contrast between 07/01/2019 and 06/30/2022. Patients with ON-T2-hyperintensity in at least one eye were included. The 2022 optic neuritis diagnostic criteria were applied to patients with noninflammatory optic neuropathies who had an ophthalmologic examination available for review. RESULTS: Of 150 patients included, 85/150 had compressive optic neuropathy; 32/150 had glaucoma; 12/150 had papilledema; 8/150 had hereditary (3), radiation-induced (3), nutritional (1), traumatic (1) optic neuropathies (none fulfilled the criteria); 13/150 had ischemic optic neuropathy and 4 fulfilled the criteria as definite optic neuritis due to contrast enhancement of the ON head. Seven additional patients would have satisfied the diagnostic criteria if red flags for alternative diagnoses had been overlooked. DISCUSSION: The application of the 2022 optic neuritis diagnostic criteria in patients with noninflammatory optic neuropathy and ON-T2-hyperintensity in at least one ON resulted in misdiagnosis of optic neuritis in only 4 patients because of ON head enhancement, all with nonarteritic anterior ischemic optic neuropathy. Neuro-ophthalmologic evaluation and exclusion of the ON head as a location in the MRI criteria would have prevented optic neuritis misdiagnosis in our study.


Asunto(s)
Imagen por Resonancia Magnética , Enfermedades del Nervio Óptico , Neuritis Óptica , Humanos , Neuritis Óptica/diagnóstico , Neuritis Óptica/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Imagen por Resonancia Magnética/normas , Anciano , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/etiología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Errores Diagnósticos , Adulto Joven
18.
Updates Surg ; 76(3): 855-868, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38647857

RESUMEN

ALPPS enables complete tumor resection in a shorter interval and a larger number of patients than classic two-stage hepatectomies. However, there is little evidence regarding long-term outcomes in patients with colorectal liver metastases (CLM). This study aims to evaluate the short and long-term outcomes of ALPPS in patients with CRM. Single-cohort, prospective, observational study. Patients with unresectable CLM due to insufficient liver remnant who underwent ALPPS between June 2011 and June 2021 were included. Of 32 patients treated, 21 were male (66%) and the median age was 56 years (range = 29-81). Both stages were completed in 30 patients (93.7%), with an R0 rate of 75% (24/32). Major morbidity was 37.5% and the mortality nil. Median overall survival (OS) and recurrence-free survival (RFS) were 28.1 and 8.8 months, respectively. The 1-3, and 5-year OS was 86%, 45%, and 21%, and RFS was 42%, 14%, and 14%, respectively. The only independent risk factor associated with poor RFS (5.7 vs 11.6 months; p = 0.038) and OS (15 vs 37 months; p = 0.009) was not receiving adjuvant chemotherapy. KRAS mutation was associated with worse OS from disease diagnosis (24.3 vs. 38.9 months; p = 0.025). ALPPS is associated with favorable oncological outcomes, comparable to traditional strategies to increase resectability in patients with CLM and high tumor burden. Our results suggest for the first time that adjuvant chemotherapy is independently associated with better short- and long-term outcomes after ALPPS. Selection of patients with KRAS mutations should be performed with caution, as this could affect oncological outcomes.


Asunto(s)
Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Persona de Mediana Edad , Hepatectomía/métodos , Masculino , Femenino , Anciano , Quimioterapia Adyuvante , Estudios Prospectivos , Adulto , Anciano de 80 o más Años , Resultado del Tratamiento , Vena Porta/cirugía , Tasa de Supervivencia , Ligadura/métodos , Factores de Tiempo
19.
Virus Res ; 339: 199282, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-37995964

RESUMEN

The effects of porcine circovirus type 2b (PCV2b) and porcine reproductive and respiratory syndrome virus (PRRSV) co-infection in epithelial cells of the swine respiratory tract is unknown. In the present study, the newborn pig trachea cell line NPTr-CD163, which is permissive to both viruses, was persistently infected with PCV2b and then with PRRSV. Viral replication, cell viability, cytokines' mRNA expression, and modulation of cellular genes expression were evaluated in infected cells. In NPTr-CD163 co-infection model, PCV2b replication was enhanced while PRRSV replication was suppressed. Cell viability was significantly decreased during PCV2b single infection and co-infection compared to mock-infected and PRRSV single infected cells. However, no difference was observed in cell viability between PCV2b and PCV2b/PRRSV infected cells. The IL6, IL8 and IL10 mRNA expression was significantly higher in co-infected cells compared to PCV2b and PRRSV single infected cells. Moreover, the IFN-α/ß expression was significantly reduced in co-infected cells compared to PCV2b infected cells whereas it remained higher compared to PRRSV infected cells. The differential gene expression analysis revealed that the mRNA expression level of the cellular gene DUSP1 was significantly higher in all PRRSV infection models compared to PCV2b single infected cells. Knockdown of DUSP1 expression in co-infected cells significantly reduced PCV2b replication, suggesting a role for DUSP1 in PCV2b/PRRSV pathogenesis.


Asunto(s)
Circovirus , Coinfección , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Enfermedades de los Porcinos , Porcinos , Animales , Circovirus/genética , Replicación Viral
20.
Eye (Lond) ; 38(9): 1626-1632, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38355669

RESUMEN

BACKGROUND/OBJECTIVES: To report a series of patients with glaucoma and optic nerve abnormalities on magnetic resonance imaging (MRI) in at least one-eye, and to determine whether these findings correlate with the severity of glaucoma. PATIENTS AND METHODS: Retrospective study of all patients who underwent a brain/orbits MRI without and with contrast at our institution between 07/1/2019-6/30/2022. Patients with optic nerve T2-hyperintensity and/or MRI optic nerve atrophy in at least one-eye and a diagnosis of isolated glaucoma in at least one-eye were included. Demographic information, glaucoma clinical characteristics, glaucoma severity parameters, and MRI indication were collected. RESULTS: Fifty-six patients (112 eyes) (age 65 years-old [range 26-88]; 70% male) had isolated bilateral glaucoma with at least one-eye MRI optic nerve abnormality. The indication for MRI was atypical/asymmetric glaucoma in 91% of patients. Of the 112 eyes, 23 had optic nerve T2-hyperintensity alone; 33 had both optic nerve T2-hyperintensity and MRI optic nerve atrophy; 34 had MRI optic nerve atrophy alone; and 22 did not have abnormal optic nerve MRI-findings. None had optic nerve enhancement. A statistically significant association between optic nerve T2-hyperintensity or MRI optic nerve atrophy and glaucoma severity parameters was found. CONCLUSIONS: Glaucoma is a clinical diagnosis and MRI brain is usually not required, except in atypical or asymmetric cases. Optic nerve T2-hyperintensity and MRI optic nerve atrophy are nonspecific MRI-findings that can be found in severe glaucomatous optic nerves and should not systematically prompt investigations for another cause of optic neuropathy.


Asunto(s)
Glaucoma , Imagen por Resonancia Magnética , Enfermedades del Nervio Óptico , Nervio Óptico , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Persona de Mediana Edad , Glaucoma/diagnóstico , Nervio Óptico/patología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/anomalías , Adulto , Enfermedades del Nervio Óptico/diagnóstico , Presión Intraocular/fisiología , Atrofia Óptica/diagnóstico , Agudeza Visual/fisiología
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