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1.
Molecules ; 29(19)2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39407499

RESUMEN

The search for natural product-based biopesticides from endophytic fungi is an effective tool to find new solutions. In this study, we studied a pre-selected fungal endophyte, isolate YCC4, from the paleoendemism Persea indica, along with compounds present in the extract and the identification of the insect antifeedant and nematicidal ones. The endophyte YCC4 was identified as Phyllosticta sp. by molecular analysis. The insect antifeedant activity was tested by choice bioassays against Spodoptera littoralis, Myzus persicae, and Rhopalosiphum padi, and the in vitro and in vivo mortality was tested against the root-knot nematode Meloidogyne javanica. Since the extract was an effective insect antifeedant, a strong nematicidal, and lacked phytotoxicity on tomato plants, a comprehensive chemical study was carried out. Two new metabolites, metguignardic acid (4) and (-)-epi-guignardone I (14), were identified along the known dioxolanones guignardic acid (1), ethyl guignardate (3), guignardianones A (5), C (2), D (7), and E (6), phenguignardic acid methyl ester (8), the meroterpenes guignardone A (9) and B (10), guignarenone B (11) and C (12), (-)-guignardone I (13), and phyllomeroterpenoid B (15). Among these compounds, 1 and 4 were effective antifeedants against S. littoralis and M. persicae, while 2 was only active on the aphid M. persicae. The nematicidal compounds were 4, 7, and 8. This is the first report on the insect antifeedant or nematicidal effects of these dioxolanone-type compounds. Since the insect antifeedant and nematicidal activity of the Phyllosticta sp. extract depend on the presence of dioxolanone components, future fermentation optimizations are needed to promote the biosynthesis of these compounds instead of meroterpenes.


Asunto(s)
Antinematodos , Endófitos , Insecticidas , Animales , Insecticidas/farmacología , Insecticidas/química , Antinematodos/farmacología , Antinematodos/química , Endófitos/química , Ascomicetos/efectos de los fármacos , Ascomicetos/química , Áfidos/efectos de los fármacos , Spodoptera/efectos de los fármacos , Spodoptera/crecimiento & desarrollo , Estructura Molecular , Solanum lycopersicum/microbiología , Solanum lycopersicum/parasitología
2.
J Cell Biol ; 223(12)2024 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-39316454

RESUMEN

Subcortical heterotopia is a cortical malformation associated with epilepsy, intellectual disability, and an excessive number of cortical neurons in the white matter. Echinoderm microtubule-associated protein like 1 (EML1) mutations lead to subcortical heterotopia, associated with abnormal radial glia positioning in the cortical wall, prior to malformation onset. This perturbed distribution of proliferative cells is likely to be a critical event for heterotopia formation; however, the underlying mechanisms remain unexplained. This study aimed to decipher the early cellular alterations leading to abnormal radial glia. In a forebrain conditional Eml1 mutant model and human patient cells, primary cilia and centrosomes are altered. Microtubule dynamics and cell cycle kinetics are also abnormal in mouse mutant radial glia. By rescuing microtubule formation in Eml1 mutant embryonic brains, abnormal radial glia delamination and heterotopia volume were significantly reduced. Thus, our new model of subcortical heterotopia reveals the causal link between Eml1's function in microtubule regulation and cell position, both critical for correct cortical development.


Asunto(s)
Centrosoma , Proteínas Asociadas a Microtúbulos , Microtúbulos , Prosencéfalo , Animales , Centrosoma/metabolismo , Humanos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Prosencéfalo/metabolismo , Prosencéfalo/patología , Prosencéfalo/embriología , Microtúbulos/metabolismo , Ratones , Cilios/metabolismo , Cilios/patología , Mutación/genética , Células Ependimogliales/metabolismo , Células Ependimogliales/patología , Ciclo Celular/genética
3.
Sci Rep ; 14(1): 19907, 2024 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198537

RESUMEN

The ability of 18F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18F-FDG uptake compared to unaffected areas (median difference > 0.6, p < 0.01). Among patients with AS, pre-treatment 18F-FDG uptake was strongly associated with disease activity (r = 0.65, p = 0.006). Longitudinal 18F-FDG scans demonstrated that decreases in uptake at 3 months were associated to clinical response (ßΔgSUVmax > 8.5, p < 0.001). We found no significant association between pre-treatment 18F-FDG uptake and subsequent clinical response. 18F-FDG PET shows potential as a marker of disease activity in AS and PsA, allowing for monitorization of biological treatment efficacy in these patients.


Asunto(s)
Artritis Psoriásica , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/diagnóstico por imagen , Artritis Psoriásica/tratamiento farmacológico , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/tratamiento farmacológico , Masculino , Femenino , Adulto , Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Biomarcadores , Radiofármacos
4.
JAMA Netw Open ; 7(7): e2421676, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39018072

RESUMEN

Importance: Labor unions are a mechanism for employee advocacy, but their role in surgery resident wellness is poorly characterized. Objective: To understand experiences with unionization among general surgery residents and residency program faculty and staff. Design, Setting, and Participants: This exploratory qualitative study included data from the Surgical Education Culture Optimization Through Targeted Interventions Based on National Comparative Data (SECOND) trial. In the exploratory phase of the SECOND trial (from March 6, 2019, to March 12, 2020), semistructured interviews about wellness were conducted with residents, faculty (attending physicians), and staff (program administrators) at 15 general surgery residency programs. Unionization was identified as an emergent theme in the interviews. Data analysis was performed from March 2019 to May 2023. Main Outcomes and Measures: The main outcome was resident and faculty experience with resident labor unions. In the qualitative analysis, lexical searches of interview transcripts identified content regarding resident labor unions. A codebook was developed inductively. Transcripts were coded by dyads, using a constant comparative approach, with differences reconciled by consensus. Results: A total of 22 interview transcripts were identified with relevant content. Of these, 19 were individual interviews conducted with residents (n = 10), faculty (n = 4), administrative staff (n = 1), a program director (n = 1), a department chair (n = 1), and designated institutional officials (n = 2), and 3 were from resident focus groups. Residents from all postgraduate year levels, including professional development (ie, research) years, were represented. Interviewees discussed resident unions at 2 programs (1 recently unionized and 1 with a decades-long history). Interviewees described the lack of voice and the lack of agency as drivers of unionization ("Residents…are trying to take control of their well-being"). Increased salary stipends and/or housing stipends were the most concretely identified union benefits. Unanticipated consequences of unionization were described by both residents and faculty, including (1) irrelevance of union-negotiated benefits to surgical residents, (2) paradoxical losses of surgery department-provided benefits, and (3) framing of resident-faculty relationships as adversarial. Union executives were noted to be nonphysician administrators whose participation in discussions about clinical education progression may increase the time and effort to remediate a resident and/or reduce educators' will to meaningfully intervene. Active surgical resident participation within the union allows for an understanding of surgical trainees' unique needs and reduced conflict. Conclusions and Relevance: In this qualitative study, unionization was a mechanism for resident voice and agency; the desire to unionize likely highlighted the lack of other such mechanisms in the training environment. However, these findings suggest that unionization may have had unintended consequences on benefits, flexibility, and teaching. Effective advocacy, whether within or outside the context of a union, was facilitated by participation from surgical residents. Future research should expand on this exploratory study by including a greater number of institutions and investigating the evolution of themes over time.


Asunto(s)
Docentes Médicos , Cirugía General , Internado y Residencia , Sindicatos , Investigación Cualitativa , Humanos , Internado y Residencia/estadística & datos numéricos , Cirugía General/educación , Docentes Médicos/estadística & datos numéricos , Masculino , Femenino , Adulto , Estados Unidos
5.
Microorganisms ; 12(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39065136

RESUMEN

In Mexico, hepatitis B and C infections are a significant burden on the health system. The aim of this narrative review was to analyze the state of the art on hepatitis B and C in Mexico by searching and studying available data in academic articles and government reports and statements on epidemiology, prevention, treatment, and elimination strategies undertaken by the Mexican government. Even where the government has implemented a hepatitis B vaccination strategy to reduce its incidence, a very low proportion of people complete the vaccination schedule. Regarding hepatitis C, there is a National Elimination Program that emphasizes the importance of screening, diagnosis, and treatment focused on the population at risk. With the implementation of this program, more than a million fast tests have been carried out and the positive cases have been verified by viral load. Infected patients are tested to determine liver function, fibrosis stage, and coinfection with HBV and/or HIV. Patients without cirrhosis and/or coinfections are treated in first-level care centers, while those with cirrhosis and/or comorbidities are referred to specialists. The possibility of hepatitis C eradication in Mexico seems more likely than eradication of hepatitis B; however, major challenges remain to be overcome to reach both infections' elimination.

6.
Sci Rep ; 14(1): 13500, 2024 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867066

RESUMEN

The continuous search for natural product-based biopesticides from fungi isolated from untapped sources is an effective tool. In this study, we studied a pre-selected fungal endophyte, isolate Aa22, from the medicinal plant Artemisia absinthium, along with the antifungal, insect antifeedant and nematicidal compounds present in the extract. The endophyte Aa22 was identified as Stemphylium solani by molecular analysis. The antifungal activity was tested by broth microdilution against Fusarium solani, F. oxysporum, F. moniliforme and Botrytis cinerea, the insect antifeedant by choice bioassays against Spodoptera littoralis, Myzus persicae and Rhopalosiphum padi and the in vitro mortality against the root-knot nematode Meloiydogyne javanica. The structures of bioactive compounds were determined on the basis of 1D and 2D NMR spectroscopy and mass spectrometry. The ethyl acetate extract obtained from the solid rice fermentation showed mycelial growth inhibition of fungal pathogens (EC50 0.08-0.31 mg/mL), was antifeedant to M. persicae (99%) and nematicidal (68% mortality). A bioguided fractionation led to the isolation of the new compound stempholone A (1), and the known stempholone B (2) and stemphol (3). These compounds exhibited antifeedant (EC50 0.50 mg/mL), antifungal (EC50 0.02-0.43 mg/L) and nematicidal (MLD 0.5 mg/mL) activities. The extract activities can be explained by 3 (antifungal), 1-3 (antifeedant) and 1 (nematicidal). Phytotoxicity tests on Lolium perenne and Lactuca sativa showed that the extract and 1 increased L. sativa root growth (121-130%) and 1 reduced L. perenne growth (48-49%). These results highlight the potential of the endophytic fungi Aa22 as biotechnological source of natural product-based biopesticides.


Asunto(s)
Antifúngicos , Antinematodos , Endófitos , Animales , Endófitos/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antinematodos/farmacología , Antinematodos/aislamiento & purificación , Antinematodos/química , Fusarium/efectos de los fármacos , Spodoptera/efectos de los fármacos , Spodoptera/crecimiento & desarrollo , Ascomicetos/efectos de los fármacos , Botrytis/efectos de los fármacos , Botrytis/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Tylenchoidea/efectos de los fármacos
7.
Int J Mol Sci ; 25(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38791100

RESUMEN

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.


Asunto(s)
Modelos Animales de Enfermedad , Metaloproteinasa 9 de la Matriz , Ozono , Enfermedad Pulmonar Obstructiva Crónica , Animales , Masculino , Ratones , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente
8.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38710465

RESUMEN

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

9.
Biogerontology ; 25(5): 819-836, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38748336

RESUMEN

An over-activation of the mechanistic target of rapamycin (mTOR) pathway promotes senescence and age-related diseases like type 2 diabetes. Besides, the regenerative potential of pancreatic islets deteriorates with aging. Nevertheless, the role of mTOR on senescence promoted by metabolic stress in islet cells as well as its relevance for electrophysiological aspects is not yet known. Here, we investigated whether parameters suggested to be indicative for senescence are induced in vitro in mouse islet cells by glucotoxicity and if mTOR inhibition plays a protective role against this. Islet cells exhibit a significant increase (~ 76%) in senescence-associated beta-galactosidase (SA-beta-gal) activity after exposure to glucotoxicity for 72 h. Glucotoxicity does not markedly influence p16INK4a protein within 72 h, but p16INK4a levels increase significantly after a 7-days incubation period. mTOR inhibition with a low rapamycin concentration (1 nM) entirely prevents the glucotoxicity-mediated increase of SA-beta-gal and p16INK4a. At the functional level, reactive oxygen species, calcium homeostasis, and electrical activity are disturbed by glucotoxicity, and rapamycin fails to prevent this. In contrast, rapamycin significantly attenuates the insulin hypersecretion promoted by glucotoxicity by modifying the mRNA levels of Vamp2 and Snap25 genes, related to insulin exocytosis. Our data indicate an influence of glucotoxicity on pancreatic islet-cell senescence and a reduction of the senescence markers by mTOR inhibition, which is relevant to preserve the regenerative potential of the islets. Decreasing the influence of mTOR on islet cells exposed to glucotoxicity attenuates insulin hypersecretion, but is not sufficient to prevent electrophysiological disturbances, indicating the involvement of mTOR-independent mechanisms.


Asunto(s)
Senescencia Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Islotes Pancreáticos , Serina-Treonina Quinasas TOR , Animales , Serina-Treonina Quinasas TOR/metabolismo , Ratones , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Senescencia Celular/efectos de los fármacos , Insulina/metabolismo , Sirolimus/farmacología , beta-Galactosidasa/metabolismo , Secreción de Insulina/efectos de los fármacos , Glucosa/metabolismo , Masculino , Ratones Endogámicos C57BL , Células Cultivadas , Especies Reactivas de Oxígeno/metabolismo
10.
Int J Mol Sci ; 25(8)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38673735

RESUMEN

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hígado , Animales , Hígado/metabolismo , Ratas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Dieta Alta en Grasa/efectos adversos , Transcriptoma , Resistencia a la Insulina/genética , Perfilación de la Expresión Génica , Estreptozocina , Modelos Animales de Enfermedad , Glucemia/metabolismo
11.
Bioresour Bioprocess ; 11(1): 28, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38647905

RESUMEN

The endophytic fungus Aspergillus sp. SPH2 was isolated from the stems of the endemic plant Bethencourtia palmensis and its extracts were found to have strong fungicidal effects against Botrytis cinerea and ixodicidal effects against Hyalomma lusitanicum at different fermentation times. In this study, the fungus was grown using three different culture media and two methodologies, Microparticulate Enhancement Cultivation (MPEC) and Semi-Solid-State Fermentation (Semi-SSF), to increase the production of secondary metabolites during submerged fermentation. The addition of an inert support to the culture medium (Semi-SSF) resulted in a significant increase in the extract production. However, when talcum powder was added to different culture media, unexpected results were observed, with a decrease in the production of the biocompounds of interest. Metabolomic analyses showed that the production of aspergillic, neoaspergillic, and neohydroxyaspergillic acids peaked in the first few days of fermentation, with notable differences observed among the methodologies and culture media. Mellein production was particularly affected by the addition of an inert support to the culture medium. These results highlight the importance of surface properties and morphology of spores and mycelia during fermentation by this fungal species.

12.
J Surg Educ ; 81(6): 794-803, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38664171

RESUMEN

OBJECTIVE: Leadership is an essential skill for surgeons, but it is not systematically taught in residency. The objective of this study was to explore the current experiences, motivators, and perspectives on leadership training of general surgery residents. DESIGN/SETTING/PARTICIPANTS: Semi-structured focus groups were conducted with 20 general surgery residents at an academic training program. Six in-person sessions (one for each postgraduate year and research) were recorded, transcribed, and de-identified. Data were inductively coded by 2 independent researchers and analyzed thematically. Discrepancies were discussed and resolved through consensus. RESULTS: Participants described developing their leadership skills prior to residency through formal (e.g., job and military) and informal (e.g., extracurricular) experiences. Most reported that leadership development during residency occurred informally (e.g., emulating mentors, trial-and-error). Evolving responsibilities and expectations shaped residents' leadership values: junior residents focused on student and task management and adaptation to new teams; mid-level residents emphasized emotional intelligence and delivery of resident feedback; and senior residents stressed team engagement, inspiring the team, and teaching/mentoring. Major transition periods between residency levels were identified as critical times for leadership training as they allow for self-reflection, motivating residents to participate in a leadership curriculum. Employing level appropriate and immediately applicable content during this time would encourage curriculum attendance and prepare residents for new roles. CONCLUSIONS: There is a lack of formal leadership training in general surgery residency. There is an opportunity to design and implement leadership training that engages surgical residents with level-relevant content and strategies. Transition periods offer optimal timing for maximal curricula uptake.


Asunto(s)
Grupos Focales , Cirugía General , Internado y Residencia , Liderazgo , Investigación Cualitativa , Humanos , Cirugía General/educación , Femenino , Masculino , Adulto , Curriculum , Educación de Postgrado en Medicina/métodos
13.
Biol Open ; 13(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38385271

RESUMEN

Although mitochondrial respiration is believed to explain a substantial part of the variation in resting metabolic rate (RMR), few studies have empirically studied the relationship between organismal and cellular metabolism. We therefore investigated the relationship between RMR and mitochondrial respiration of permeabilized blood cells in wild great tits (Parus major L.). We also studied the correlation between mitochondrial respiration traits and blood cell count, as normalizing mitochondrial respiration by the cell count is a method commonly used to study blood metabolism. In contrast to previous studies, our results show that there was no relationship between RMR and mitochondrial respiration in intact blood cells (i.e. with the ROUTINE respiration). However, when cells were permeabilized and interrelation re-assessed under saturating substrate availability, we found that RMR was positively related to phosphorylating respiration rates through complexes I and II (i.e. OXPHOS respiration) and to the mitochondrial efficiency to produce energy (i.e. net phosphorylation efficiency), though variation explained by the models was low (i.e. linear model: R2=0.14 to 0.21). However, unlike studies in mammals, LEAK respiration without [i.e. L(n)] and with [i.e. L(Omy)] adenylates was not significantly related to RMR. These results suggest that phosphorylating respiration in blood cells can potentially be used to predict RMR in wild birds, but that this relationship may have to be addressed in standardized conditions (permeabilized cells) and that the prediction risks being imprecise. We also showed that, in our conditions, there was no relationship between any mitochondrial respiration trait and blood cell count. Hence, we caution against normalising respiration rates using this parameter as is sometimes done. Future work should address the functional explanations for the observed relationships, and determine why these appear labile across space, time, taxon, and physiological state.


Asunto(s)
Metabolismo Basal , Metabolismo Energético , Animales , Metabolismo Basal/fisiología , Mitocondrias , Respiración , Recuento de Células Sanguíneas , Mamíferos
14.
Histol Histopathol ; 39(7): 805-816, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38226432

RESUMEN

The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-ß/Smad or Wnt/ß-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.


Asunto(s)
Bronquitis Crónica , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/patología , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Bronquitis Crónica/metabolismo , Bronquitis Crónica/patología , Bronquitis Crónica/genética , Animales , Transducción de Señal
15.
Animals (Basel) ; 13(23)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38067068

RESUMEN

Ozone-therapy is used in humans as a coadjutant treatment in intervertebral disc diseases due to its analgesic, anti-inflammatory and antioxidant effects. References in dogs are scarce and limited to clinical cases (intradiscal/paravertebral infiltrations). The aim of this study was to assess the use of medical ozone (MO) as an adjunctive treatment in dogs with intervertebral disc protrusions (Hansen Type II/Chronic). A retrospective study was conducted in dogs diagnosed with intervertebral disc protrusions by MRI/CT in which MO was used as an adjuvant therapy to conventional medical treatment. Neurological examination and quality of life (QL) at the beginning and end of study were recorded, as well as posology and possible side effects. A total of 21 patients of different breeds and sex with a mean age of 12 years were included in this study. Results showed pain relief (7 ± 3 days) and improvement of neurologic signs (11 ± 9 days) with a consequent increasement in QL (13 ± 9 days). Thirteen out of the twenty-one patients (62%) showed a complete remission of the clinical signs. No serious adverse effects were observed. Medical ozone could be a potential complementary therapy to medical treatment in dogs with intervertebral disc protrusions. Prospective studies are necessary.

16.
BMJ Open ; 13(12): e075470, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38097232

RESUMEN

OBJECTIVE: Poor interdisciplinary care team communication has been associated with increased mortality. The study aimed to define conditions for effective interdisciplinary care team communication. DESIGN: An observational cross-sectional qualitative study. SETTING: A surgical intensive care unit in a large, urban, academic referral medical centre. PARTICIPANTS: A total 6 interviews and 10 focus groups from February to June 2021 (N=33) were performed. Interdisciplinary clinicians who cared for critically ill patients were interviewed. Participants included intensivist, transplant, colorectal, vascular, surgical oncology, trauma faculty surgeons (n=10); emergency medicine, surgery, gynaecology, radiology physicians-in-training (n=6), advanced practice providers (n=5), nurses (n=7), fellows (n=1) and subspecialist clinicians such as respiratory therapists, pharmacists and dieticians (n=4). Audiorecorded content of interviews and focus groups were deidentified and transcribed verbatim. The study team iteratively generated the codebook. All transcripts were independently coded by two team members. PRIMARY OUTCOME: Conditions for effective interdisciplinary care team communication. RESULTS: We identified five themes relating to conditions for effective interdisciplinary care team communication in our surgical intensive care unit setting: role definition, formal processes, informal communication pathways, hierarchical influences and psychological safety. Participants reported that clear role definition and standardised formal communication processes empowered clinicians to engage in discussions that mitigated hierarchy and facilitated psychological safety. CONCLUSIONS: Standardising communication and creating defined roles in formal processes can promote effective interdisciplinary care team communication by fostering psychological safety.


Asunto(s)
Comunicación Interdisciplinaria , Grupo de Atención al Paciente , Humanos , Estudios Transversales , Investigación Cualitativa , Unidades de Cuidados Intensivos , Comunicación , Cuidados Críticos
17.
EJNMMI Phys ; 10(1): 50, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37665476

RESUMEN

BACKGROUND: As for any other nuclear medicine treatment, patients treated with [177Lu]Lu-DOTA-TATE should be given some radiation protection recommendations after being discharged to limit the dose received by family members and public. The restriction periods will depend on the remaining activity at the time of discharge, the washout rate and patients' personal conditions. The activity in patients' whole-body follows a bi-exponential behaviour. At the time of discharge only the first part of the time-activity curve is known. However, the second phase of the bi-exponential curve should be known to individualize the time of restrictions. The main purpose of this prospective study was to establish a simple method for calculating the restriction periods based on measurements taken before discharge. METHODS: The whole-body time-activity curve was calculated for 20 patients from dose-rate measurements performed during the first week post-administration. An effective decay time [Formula: see text] was calculated from a mono-exponential fit performed with the 6 h and 24 h measurements and compared with the effective decay time [Formula: see text] obtained from the mono-exponential fit performed with the 24 h, 48 h and 168 h measurements. The differences between them were calculated and the 95th percentile of these differences was used as a correction factor for [Formula: see text]. A modified effective decay [Formula: see text] was obtained by adding the correction factor to [Formula: see text] and the restriction periods for each patient was calculated. The whole body activity washout between the first and the fourth treatment cycles of 16 patients was also compared. RESULTS: The comparison of the whole-body activity curves between the first and the fourth cycle of the treatment for 16 patients would indicate that the recommendations on radiation protection determined from the first cycle could reasonably be used for the remaining cycles in most patients. The values of [Formula: see text] and [Formula: see text] obtained for the 20 patients were significantly different. The 95th percentile of the differences between [Formula: see text] and [Formula: see text] was 46 h, which is thus the time to be added to [Formula: see text] so as to determine the restriction periods. CONCLUSIONS: The proposed method makes it possible to calculate the restriction periods for patients treated with [177Lu]Lu-DOTA-TATE before they leave the hospital in a conservative and individualized way.

18.
J Comp Neurol ; 531(16): 1715-1750, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37695031

RESUMEN

The globus pallidus (GP) of primates is divided conventionally into distinct internal and external parts. The literature repeats since 1930 the opinion that the homolog of the primate internal pallidum in rodents is the hypothalamic entopeduncular nucleus (embedded within fiber tracts of the cerebral peduncle). To test this idea, we explored its historic fundaments, checked the development and genoarchitecture of mouse entopeduncular and pallidal neurons, and examined relevant comparative connectivity data. We found that the extratelencephalic mouse entopeduncular structure consists of four different components arrayed along a dorsoventral sequence in the alar hypothalamus. The ventral entopeduncular nucleus (EPV), with GABAergic neurons expressing Dlx5&6 and Nkx2-1, lies within the hypothalamic peduncular subparaventricular area. Three other formations-the dorsal entopeduncular nucleus (EPD), the prereticular entopeduncular nucleus (EPPRt ), and the preeminential entopeduncular nucleus (EPPEm )-lie within the overlying paraventricular area, under the subpallium. EPD contains glutamatergic neurons expressing Tbr1, Otp, and Pax6. The EPPRt has GABAergic cells expressing Isl1 and Meis2, whereas the EPPEm population expresses Foxg1 and may be glutamatergic. Genoarchitectonic observations on relevant areas of the mouse pallidal/diagonal subpallium suggest that the GP of rodents is constituted as in primates by two adjacent but molecularly and hodologically differentiable telencephalic portions (both expressing Foxg1). These and other reported data oppose the notion that the rodent extratelencephalic entopeduncular nucleus is homologous to the primate internal pallidum. We suggest instead that all mammals, including rodents, have dual subpallial GP components, whereas primates probably also have a comparable set of hypothalamic entopeduncular nuclei. Remarkably, there is close similarity in some gene expression properties of the telencephalic internal GP and the hypothalamic EPV. This apparently underlies their notable functional analogy, sharing GABAergic neurons and thalamopetal connectivity.


Asunto(s)
Globo Pálido , Roedores , Animales , Ratones , Núcleo Entopeduncular , Hipotálamo , Primates , Neuronas GABAérgicas , Factores de Transcripción/genética , Proteínas del Tejido Nervioso , Factores de Transcripción Forkhead
19.
Medisan ; 27(3)jun. 2023. tab
Artículo en Español | LILACS, CUMED | ID: biblio-1514549

RESUMEN

Introducción: A la Universidad del siglo XXI le corresponde ser consecuente con los procesos derivados del desarrollo social, lo cual debe ser atendido desde la formación de posgrado. A tales efectos, se diseñó y ejecutó una estrategia de superación en la Facultad de Tecnología de la Salud de La Habana, según las necesidades de aprendizaje de los profesionales. Objetivo: Describir los principales resultados de la generalización de la escalera de superación académica con enfoque interdisciplinario. Métodos: Se realizó un estudio descriptivo, longitudinal y retrospectivo, en el periodo 2017-2022, en la Facultad de Tecnología de la Salud de La Habana. Las 5 variables identificadas fueron la superación por tipo de actividad de posgrado según año, los artículos científicos publicados por año en la Revista Cubana de Tecnología de la Salud, la formación de doctores en educación médica, los doctores en educación médica graduados según universidades y centros de salud, así como la promoción de profesores a la categoría docente superior. Resultados: Se apreció un incremento de las formas de superación desarrolladas. En el 2019 la cifra de autores y coautores con publicaciones en la revista de la Facultad ascendió a 219; asimismo, en la formación de grado científico hubo considerables resultados, tanto en profesores como en otros profesionales de la salud, y aumentó el número de docentes que ascendieron a la categoría superior. Conclusiones: Como resultado de la superación académica escalonada se destacó la elaboración de 5 maestrías para el área de las tecnologías de la salud y se apreció un incremento sostenido en la promoción de profesionales de la educación médica a categorías docentes superiores.


Introduction: The University of the XXI century is in charge of being consequent with the processes derived from the social development, which should be assisted from the posdegree education. To such effects, a training strategy was designed and implemented in the Health Technology Faculty of Havana city, according to the learning necessities of professionals. Objective: To describe the main results of generalization of the academic training steps with interdisciplinary approach. Methods: A descriptive, longitudinal and retrospective study was carried out in 2017-2022 in the Health Technology Faculty of Havana city. The 5 variables identified were training by type of posdegree activity according to year, the scientific works published per year in the Cuban Journal of Health Technology, training of doctors in Medical Education, doctors in Medical Education graduated according to universities and health centers, as well as the promotion of professors to the superior teaching category. Results: An increment in the developed ways of training was appreciated. In 2019, the number of authors and joint authors with publications in the Faculty's journal has reached 219; also, there were considerable results in the scientific degree education, either in professors or in other health professionals, and there was a higher number of professors that reached the superior category. Conclusions: As a result of the staged academic training, the elaboration of 5 masters՚ degree for health technologies area was notable and a sustained increment was appreciated in the promotion of professionals from the medical education to superior educational categories.

20.
Surgery ; 174(2): 350-355, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37211509

RESUMEN

BACKGROUND: Better information sharing in intensive care units has been associated with lower risk-adjusted mortality. This study explored how team characteristics and leadership are associated with information sharing in 4 intensive care units in a single large urban, academic medical center. METHODS: A qualitative study was conducted to understand how team characteristics and leadership are associated with information sharing. Qualitative data were conducted through ethnographic observations. One postdoctoral research fellow and one PhD qualitative researcher conducted nonparticipant observations of a Medical, Surgical, Neurological, and Cardiothoracic intensive care unit morning and afternoon rounds, as well as nurse and resident handoffs from May to September 2021. Field notes of observations were thematically analyzed using deductive reasoning anchored to the Edmondson Team Learning Model. This study included nurses, physicians (ie, intensivists, surgeons, fellows, and residents), medical students, pharmacists, respiratory therapists, dieticians, physical therapists, physician assistants, and nurse practitioners. RESULTS: We conducted 50 person-hours of observations involving 148 providers. Three themes emerged from the qualitative analysis: (1) team leaders used variable leadership techniques to involve team members in discussions for information sharing related to patient care, (2) predefined tasks for team members allowed them to prepare for effective information sharing during intensive care unit rounds, and (3) a psychologically safe environment allowed team members to participate in discussions for information sharing related to patient care. CONCLUSION: Inclusive team leadership is foundational in creating a psychologically safe environment for effective information sharing.


Asunto(s)
Liderazgo , Cirujanos , Humanos , Grupo de Atención al Paciente , Unidades de Cuidados Intensivos , Investigación Cualitativa , Difusión de la Información
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