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1.
Trials ; 25(1): 647, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358750

RESUMEN

BACKGROUND: Pelvic organ prolapse (POP) is one of the most common pathologies of the pelvic floor, and it can be found among 40-60% of women who have given birth. Correction of the defect of the DeLancey level II without reconstruction of the apical defect is doomed to failure. Also, in the structure of pelvic floor defects, there is often an incompetency of the perineal body, as a consequence of traumatic delivery. Perineoplasty is considered to be the main method of correction for perineal body incompetency. However, it is worth mentioning that there are no randomized trials, which estimate the influence of simultaneous correction of the perineal body on the effectiveness of transvaginal apical fixation. METHODS: It is planned to include 310 patients in this trial. Patients who met the inclusion/exclusion criteria will be randomized into 2 groups: 1st group-patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy without perineoplasty, 2nd group-patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy and perineoplasty. Patients will be called to an appointment 6, 12, and 24 months after discharge. DISCUSSION: The aim of this trial is to evaluate the efficiency and safety of simultaneous perineoplasty on the clinical and anatomical efficacy of mesh-augmented sacrospinal fixation in advanced pelvic organ prolapse repair. Based on previous studies, it was difficult to estimate and comprehend whether colpoperinoplasty actually reduces the risk of prolapse recurrence. TRIAL REGISTRATION: NCT05422209. Registered on 18 May 2022.


Asunto(s)
Prolapso de Órgano Pélvico , Perineo , Mallas Quirúrgicas , Humanos , Femenino , Prolapso de Órgano Pélvico/cirugía , Resultado del Tratamiento , Perineo/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Vagina/cirugía , Procedimientos Quirúrgicos Ginecológicos/métodos , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Persona de Mediana Edad , Diafragma Pélvico/cirugía , Factores de Tiempo , Adulto , Anciano
2.
Cogn Res Princ Implic ; 9(1): 68, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39379600

RESUMEN

Searching for missing or wanted people is a crucial task in our society. Previous work on prospective person memory (PPM) has demonstrated that performance on this type of search task is worse relative to standard prospective memory tasks. Importantly, this process may be further affected by the race of the missing person, yet this has never been tested in laboratory settings. To test the effects of race on PPM, a convenience sample consisting primarily of self-identified Caucasian participants was asked to search for either a Caucasian or an Indian target person while judging the orientation of different Caucasian and Indian faces. Although the tasks were otherwise identical, 89% of Caucasian PPM targets were found while only 53% of Indian targets were found. Furthermore, relative to a control group with no PPM requirements, participants were slower and more error-prone when judging Indian faces relative to White faces, particularly if they were searching for an Indian face. We interpret these results as revealing other-race effects in prospective person memory, highlighting race as a critical factor for finding missing people. Importantly, this also emphasizes the need for real-world search efforts to factor in difficulty differences when people monitor for missing/wanted people from their own or different racial backgrounds. For example, media coverage of missing persons cases could perhaps be distributed more equitably by considering whether the missing person is from a racial minority in that region.


Asunto(s)
Memoria Episódica , Racismo , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Racismo/etnología , Población Blanca/etnología , Reconocimiento Facial/fisiología
4.
Biomolecules ; 14(5)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38785957

RESUMEN

RAMOSA1 (RA1) is a Cys2-His2-type (C2H2) zinc finger transcription factor that controls plant meristem fate and identity and has played an important role in maize domestication. Despite its importance, the origin of RA1 is unknown, and the evolution in plants is only partially understood. In this paper, we present a well-resolved phylogeny based on 73 amino acid sequences from 48 embryophyte species. The recovered tree topology indicates that, during grass evolution, RA1 arose from two consecutive SUPERMAN duplications, resulting in three distinct grass sequence lineages: RA1-like A, RA1-like B, and RA1; however, most of these copies have unknown functions. Our findings indicate that RA1 and RA1-like play roles in the nucleus despite lacking a traditional nuclear localization signal. Here, we report that copies diversified their coding region and, with it, their protein structure, suggesting different patterns of DNA binding and protein-protein interaction. In addition, each of the retained copies diversified regulatory elements along their promoter regions, indicating differences in their upstream regulation. Taken together, the evidence indicates that the RA1 and RA1-like gene families in grasses underwent subfunctionalization and neofunctionalization enabled by gene duplication.


Asunto(s)
Evolución Molecular , Filogenia , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Embryophyta/genética , Embryophyta/metabolismo , Secuencia de Aminoácidos
5.
BMC Biol ; 22(1): 115, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764040

RESUMEN

BACKGROUND: Thromboinflammation is caused by mutual activation of platelets and neutrophils. The site of thromboinflammation is determined by chemoattracting agents release by endothelium, immune cells, and platelets. Impaired neutrophil chemotaxis contributes to the pathogenesis of Shwachman-Diamond syndrome (SDS). In this hereditary disorder, neutrophils are known to have aberrant chemoattractant-induced F-actin properties. Here, we aim to determine whether neutrophil chemotaxis could be analyzed using our previously developed ex vivo assay of the neutrophils crawling among the growing thrombi. METHODS: Adult and pediatric healthy donors, alongside with pediatric patients with SDS, were recruited for the study. Thrombus formation and granulocyte movement in hirudinated whole blood were visualized by fluorescent microscopy in fibrillar collagen-coated parallel-plate flow chambers. Alternatively, fibrinogen, fibronectin, vWF, or single tumor cells immobilized on coverslips were used. A computational model of chemokine distribution in flow chamber with a virtual neutrophil moving in it was used to analyze the observed data. RESULTS: The movement of healthy donor neutrophils predominantly occurred in the direction and vicinity of thrombi grown on collagen or around tumor cells. For SDS patients or on coatings other than collagen, the movement was characterized by randomness and significantly reduced velocities. Increase in wall shear rates to 300-500 1/s led to an increase in the proportion of rolling neutrophils. A stochastic algorithm simulating leucocyte chemotaxis movement in the calculated chemoattractant field could reproduce the experimental trajectories of moving neutrophils for 72% of cells. CONCLUSIONS: In samples from healthy donors, but not SDS patients, neutrophils move in the direction of large, chemoattractant-releasing platelet thrombi growing on collagen.


Asunto(s)
Neutrófilos , Trombosis , Humanos , Neutrófilos/fisiología , Trombosis/fisiopatología , Quimiotaxis , Adulto , Niño , Masculino , Quimiotaxis de Leucocito , Femenino , Movimiento Celular
6.
bioRxiv ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38585911

RESUMEN

GABA A receptors containing δ subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, δ subunits are expressed on the surface of some pyramidal cells as well as on parvalbumin positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG; however, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity. After confirming a loss of functional δ mediated tonic currents in PV cells in cortical slices from mice lacking Gabrd in PV+ neurons (PV δcKO), we performed EEG recordings to survey network activity across wake and sleep states. PV δcKO mice showed altered spectral content of EEG during NREM and REM sleep that was a result of increased oscillatory activity in NREM and the emergence of transient high amplitude bursts of theta frequency activity during REM. Viral reintroduction of Gabrd to PV+ interneurons in PV δcKO mice rescued REM EEG phenotypes, supporting an important role for δ subunit mediated inhibition of PV+ interneurons for maintaining normal REM cortical oscillations. Significance statement: The impact on cortical EEG of inhibition on PV+ neurons was studied by deleting a GABA A receptor subunit selectively from these neurons. We discovered unexpected changes at low frequencies during sleep that were rescued by viral reintroduction.

7.
Biochemistry (Mosc) ; 89(3): 462-473, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38648766

RESUMEN

Structural organization of HIV-1 integrase is based on a tetramer formed by two protein dimers. Within this tetramer, the catalytic domain of one subunit of the first dimer interacts with the N-terminal domain of the second dimer subunit. It is the tetrameric structure that allows both ends of the viral DNA to be correctly positioned relative to the cellular DNA and to realize catalytic functions of integrase, namely 3'-processing and strand transfer. However, during the HIV-1 replicative cycle, integrase is responsible not only for the integration stage, it is also involved in reverse transcription and is necessary at the stage of capsid formation of the newly formed virions. It has been suggested that HIV-1 integrase is a structurally dynamic protein and its biological functions depend on its structure. Accordingly, studying interactions between the domains of integrase that provide its tetrameric structure is important for understanding its multiple functions. In this work, we investigated the role of three amino acids of the catalytic domain, I182, R187, and K188, located in the contact region of two integrase dimers in the tetramer structure, in reverse transcription and integration. It has been shown that the R187 residue is extremely important for formation of the correct integrase structure, which is necessary at all stages of its functional activity. The I182 residue is necessary for successful integration and is not important for reverse transcription, while the K188 residue, on the contrary, is involved in formation of the integrase structure, which is important for the effective reverse transcription.


Asunto(s)
Dominio Catalítico , Integrasa de VIH , VIH-1 , Transcripción Reversa , Integración Viral , Integrasa de VIH/metabolismo , Integrasa de VIH/química , Integrasa de VIH/genética , VIH-1/enzimología , Humanos
8.
Nat Commun ; 15(1): 2856, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565851

RESUMEN

Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution, a process characterized by reduction of BAT mass and function with increased lipid droplet size. Single nuclei RNA sequencing of aged mice identifies a specific brown adipocyte population of Ucp1-low cells that are pyroptotic and display a reduction in the longevity gene syntaxin 4 (Stx4a). Similar to aged brown adipocytes, Ucp1-STX4KO mice display loss of brown adipose tissue mass and thermogenic dysfunction concomitant with increased pyroptosis. Restoration of STX4 expression or suppression of pyroptosis activation protects against the decline in both mass and thermogenic activity in the aged and Ucp1-STX4KO mice. Mechanistically, STX4 deficiency reduces oxidative phosphorylation, glucose uptake, and glycolysis leading to reduced ATP levels, a known triggering signal for pyroptosis. Together, these data demonstrate an understanding of rapid brown adipocyte involution and that physiologic aging and thermogenic dysfunction result from pyroptotic signaling activation.


Asunto(s)
Tejido Adiposo Pardo , Piroptosis , Animales , Ratones , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Transducción de Señal , Termogénesis/fisiología , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
9.
Biomolecules ; 14(3)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38540675

RESUMEN

Brain cholesterol metabolic products include neurosteroids and oxysterols, which play important roles in cellular physiology. In neurons, the cholesterol oxidation product, 24S-hydroxycholesterol (24S-HC), is a regulator of signaling and transcription. Here, we examined the behavioral effects of 24S-HC loss, using global and cell-selective genetic deletion of the synthetic enzyme CYP46A1. Mice that are globally deficient in CYP46A1 exhibited hypoactivity at young ages and unexpected increases in conditioned fear memory. Despite strong reductions in hippocampal 24S-HC in mice with selective loss of CYP46A1 in VGLUT1-positive cells, behavioral effects were not recapitulated in these conditional knockout mice. Global knockout produced strong, developmentally dependent transcriptional effects on select cholesterol metabolism genes. These included paradoxical changes in Liver X Receptor targets. Again, conditional knockout was insufficient to recapitulate most changes. Overall, our results highlight the complex effects of 24S-HC in an in vivo setting that are not fully predicted by known mechanisms. The results also demonstrate that the complete inhibition of enzymatic activity may be needed for a detectable, therapeutically relevant impact on gene expression and behavior.


Asunto(s)
Colesterol , Hidroxicolesteroles , Ratones , Animales , Colesterol 24-Hidroxilasa/metabolismo , Hidroxicolesteroles/metabolismo , Colesterol/metabolismo , Hipocampo/metabolismo
10.
J Neurophysiol ; 131(3): 529-540, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38323322

RESUMEN

Cortical electroencephalograms (EEGs) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/f) of EEG power spectra is often treated as noise, but recent studies suggest that changes to the aperiodic exponent of power spectra may reflect changes in excitation/inhibition balance, a concept linked to antidepressant effects, epilepsy, autism, and other clinical conditions. One confound of previous studies is behavioral state, because factors associated with behavioral state other than excitation/inhibition ratio may alter EEG parameters. Thus, to test the robustness of the aperiodic exponent as a predictor of excitation/inhibition ratio, we analyzed video-EEG during active exploration in mice of both sexes during various pharmacological manipulations with the fitting oscillations and one over f (FOOOF) algorithm. We found that GABAA receptor (GABAAR)-positive allosteric modulators increased the aperiodic exponent, consistent with the hypothesis that an increased exponent signals enhanced cortical inhibition, but other drugs (ketamine and GABAAR antagonists at subconvulsive doses) did not follow the prediction. To tilt excitation/inhibition ratio more selectively toward excitation, we suppressed the activity of parvalbumin-positive interneurons with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Contrary to our expectations, circuit disinhibition with the DREADD increased the aperiodic exponent. We conclude that the aperiodic exponent of EEG power spectra does not yield a universally reliable marker of cortical excitation/inhibition ratio.NEW & NOTEWORTHY Neuropsychiatric illness may be associated with altered excitation/inhibition balance. A single electroencephalogram (EEG) parameter, the aperiodic exponent of power spectra, may predict the ratio between excitation and inhibition. Here, we use cortical EEGs in mice to evaluate this hypothesis, using pharmacological manipulations of known mechanism. We show that the aperiodic exponent of EEG power spectra is not a reliable marker of excitation/inhibition ratio. Thus, alternative markers of this ratio must be sought.


Asunto(s)
Electroencefalografía , Ketamina , Masculino , Femenino , Ratones , Animales , Receptores de GABA-A , Ketamina/farmacología , Ácido gamma-Aminobutírico
11.
Phys Chem Chem Phys ; 26(10): 8038-8042, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38379506

RESUMEN

Two novel derivatives of the C70 fullerene with 9- and 10-membered cage openings were obtained by means of oxidation and decarbonylation of C70(CF3)8. The major product, C70(O)(CF3)8O2, features a cleaved C-C bond transformed into two carbonyl functions plus an ether bridge. The second product, C69O(CF3)8O, has one of the carbonyls replaced with another ether bridge. We provide a DFT analysis of the possible formation pathways to give the oxidized compounds under the action of pyridine N-oxide.

12.
Medicina (B Aires) ; 84(1): 87-95, 2024.
Artículo en Español | MEDLINE | ID: mdl-38271935

RESUMEN

INTRODUCTION: The Global Trigger Tool (GTT) is a tool that accurately identifies adverse events that represent a significant problem in hospitals. METHODS: Cross-sectional study based on retrospective review of randomized medical records using the GTT tool. RESULTS: A total of 161 adverse events (AEs) were detected: 51 events per 100 admissions, 66 per 1000 patient-days, and 30% of admissions with AEs. The most frequent triggers were from the care module, with 25% complications associated with the use of procedures, 10% pressure ulcers, and 9% care-associated infections. The presence of AEs had a statistically significant association with a stay of more than 5 days, and a moderate association with age and number of triggers. Regarding the damage, 78% of the patients presented mild events and 4% fatal events. The ROC curves analysis showed that the triggers with the greatest area under the curve were: procedural complication (0.70), pressure ulcers (0.61) and rapid response code (0.60). DISCUSSION: The number of events per 100 admissions was higher than that reported in the literature, but there were no differences in events per 1000 patientdays. Fatal cases were caused by respiratory infectious diseases in patients with comorbidities, nasogastric tube needs and cognitive decline. The study highlights the scarce use of the tool in public hospitals and the implementation of trigger analysis with ROC curves. Knowing the frequency and the most frequent type of event will allow the implementation of measures that improve patient safety.


Introducción: El Global Trigger Tool (GTT) es una herramienta que identifica con precisión los eventos adversos, estos representan un problema relevante y prevenible en los hospitales. Métodos: Estudio de corte transversal basado en la revisión retrospectiva de historias clínicas aleatorizadas utilizando el GTT. Resultados: Se detectaron 161 eventos adversos (EA): 51 por cada 100 admisiones, 66 por cada 1000 días paciente y 30% de admisiones con EA. Los disparadores más frecuentes fueron del módulo cuidados, 25% complicaciones asociadas al uso de procedimientos, 10% úlceras por presión y 9% infecciones asociadas a la atención. La presencia de EA tuvo asociación estadísticamente significativa con estancia mayor a 5 días, y asociación moderada con edad y número de disparadores. En cuanto al daño, 78% de los pacientes presentaron eventos leves y 4% eventos fatales. En el análisis con curvas ROC, los disparadores con mayor área bajo la curva fueron: complicación de procedimientos (0.70), úlceras por presión (0.61) y código de respuesta rápida (0.60). Discusión: Los eventos por 100 admisiones fueron superiores a la bibliografía pero no hubo diferencias en eventos por cada 1000 días paciente. Los casos fatales se produjeron por enfermedades infecciosas respiratorias en pacientes con comorbilidades, necesidad de sonda nasogástrica y deterioro cognitivo. Se destaca la escasa aplicación de la herramienta en hospitales públicos, y la implementación de análisis de disparadores con curvas ROC. Conocer la frecuencia y el tipo de evento más frecuente permitirá implementar medidas que mejoren la seguridad de los pacientes.


Asunto(s)
Úlcera por Presión , Humanos , Estudios Transversales , Úlcera por Presión/epidemiología , Seguridad del Paciente , Hospitalización , Registros Médicos , Estudios Retrospectivos
13.
Sci Rep ; 14(1): 1042, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38200205

RESUMEN

Neuropsychiatric and neurodegenerative disorders are correlated with cellular stress. Macroautophagy (autophagy) may represent an important protective pathway to maintain cellular homeostasis and functionality, as it targets cytoplasmic components to lysosomes for degradation and recycling. Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, brexanolone), may induce autophagy, we stably transfected human embryonic kidney 293 (HEK) cells with a ratiometric fluorescent probe to assay NAS effects on autophagy. We hypothesized that NAS may modulate autophagy in part by the ability of uncharged NAS to readily permeate membranes. Microscopy revealed a weak effect of AlloP on autophagic flux compared with the positive control treatment of Torin1. In high-throughput microplate experiments, we found that autophagy induction was more robust in early passages of HEK cells. Despite limiting studies to early passages for maximum sensitivity, a range of NAS structures failed to reliably induce autophagy or interact with Torin1 or starvation effects. To probe NAS in a system where AlloP effects have been shown previously, we surveyed astrocytes and again saw minimal autophagy induction by AlloP. Combined with other published results, our results suggest that NAS may modulate autophagy in a cell-specific or context-specific manner. Although there is merit to cell lines as a screening tool, future studies may require assaying NAS in cells from brain regions involved in neuropsychiatric disorders.


Asunto(s)
Neuroesteroides , Humanos , Autofagia , Macroautofagia , Riñón , Lisosomas
14.
Medicina (B.Aires) ; Medicina (B.Aires);84(1): 87-95, 2024. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1558453

RESUMEN

Resumen Introducción : El Global Trigger Tool (GTT) es una herramienta que identifica con precisión los eventos adversos, estos representan un problema relevante y prevenible en los hospitales. Métodos : Estudio de corte transversal basado en la revisión retrospectiva de historias clínicas aleatorizadas utilizando el GTT. Resultados : Se detectaron 161 eventos adversos (EA): 51 por cada 100 admisiones, 66 por cada 1000 días pa ciente y 30% de admisiones con EA. Los disparadores más frecuentes fueron del módulo cuidados, 25% com plicaciones asociadas al uso de procedimientos, 10% úlceras por presión y 9% infecciones asociadas a la atención. La presencia de EA tuvo asociación estadís ticamente significativa con estancia mayor a 5 días, y asociación moderada con edad y número de disparado res. En cuanto al daño, 78% de los pacientes presentaron eventos leves y 4% eventos fatales. En el análisis con cur vas ROC, los disparadores con mayor área bajo la curva fueron: complicación de procedimientos (0.70), úlceras por presión (0.61) y código de respuesta rápida (0.60). Discusión : Los eventos por 100 admisiones fueron superiores a la bibliografía pero no hubo diferencias en eventos por cada 1000 días paciente. Los casos fatales se produjeron por enfermedades infecciosas respiratorias en pacientes con comorbilidades, necesidad de sonda nasogástrica y deterioro cognitivo. Se destaca la escasa aplicación de la herramienta en hospitales públicos, y la implementación de análisis de disparadores con cur vas ROC. Conocer la frecuencia y el tipo de evento más frecuente permitirá implementar medidas que mejoren la seguridad de los pacientes.


Abstract Introduction : The Global Trigger Tool (GTT) is a tool that accurately identifies adverse events that represent a significant problem in hospitals. Methods : Cross-sectional study based on retrospec tive review of randomized medical records using the GTT tool. Results : A total of 161 adverse events (AEs) were detected: 51 events per 100 admissions, 66 per 1000 patient-days, and 30% of admissions with AEs. The most frequent triggers were from the care module, with 25% complications associated with the use of procedures, 10% pressure ulcers, and 9% care-associated infections. The presence of AEs had a statistically significant asso ciation with a stay of more than 5 days, and a moderate association with age and number of triggers. Regarding the damage, 78% of the patients presented mild events and 4% fatal events. The ROC curves analysis showed that the triggers with the greatest area under the curve were: procedural complication (0.70), pressure ulcers (0.61) and rapid response code (0.60). Discussion : The number of events per 100 admis sions was higher than that reported in the literature, but there were no differences in events per 1000 patient-days. Fatal cases were caused by respiratory infectious diseases in patients with comorbidities, nasogastric tube needs and cognitive decline. The study highlights the scarce use of the tool in public hospitals and the implementation of trigger analysis with ROC curves. Knowing the frequency and the most frequent type of event will allow the implementation of measures that improve patient safety.

15.
bioRxiv ; 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37790570

RESUMEN

Cortical electroencephalograms (EEG) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/ f ) of EEG power spectra is often treated as noise, but recent studies suggest that changes to the aperiodic exponent of power spectra may reflect changes in excitation/inhibition (E/I) balance, a concept linked to antidepressant effects, epilepsy, autism, and other clinical conditions. One confound of previous studies is behavioral state, because factors associated with behavioral state other than E/I ratio may alter EEG parameters. Thus, to test the robustness of the aperiodic exponent as a predictor of E/I ratio, we analyzed active exploration in mice using video EEG following various pharmacological manipulations with the Fitting Oscillations & One Over F (FOOOF) algorithm. We found that GABA A receptor (GABA A R) positive allosteric modulators increased the aperiodic exponent, consistent with the hypothesis that an increased exponent signals enhanced cortical inhibition, but other drugs (ketamine and GABA A R antagonists at sub-convulsive doses) did not follow the prediction. To tilt E/I ratio more selectively toward excitation, we suppressed the activity of parvalbumin (PV) interneurons with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Contrary to our expectations and studies demonstrating increased cortical activity following PV suppression, circuit disinhibition with the DREADD increased the aperiodic exponent. We conclude that the aperiodic exponent of EEG power spectra does not yield a universally reliable marker of E/I ratio. Alternatively, the concept of E/I state may be sufficiently oversimplified that it cannot be mapped readily onto an EEG parameter. Significance StateBment: Neuropsychiatric illness is widely prevalent and debilitating. Causes are not well understood, but some hypotheses point toward altered excitation/inhibition (E/I) balance. Here, we use cortical electroencephalograms (EEG) in mice, given applicability of cortical EEG across species, and evaluate the impact of validated drugs, including anxiolytics (pentobarbital and diazepam), along with novel rapid-acting antidepressants (ketamine and allopregnanolone). We focus on analyzing the aperiodic component of EEG power spectra, which may be associated with changes in E/I ratio. We show that aperiodic exponent of EEG power spectra is not a reliable marker of E/I ratio. Moreover, the concept of E/I ratio may be too broad and complex to be defined by an EEG parameter.

16.
Nanomedicine (Lond) ; 18(10): 803-818, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37254888

RESUMEN

Aim: This work aimed to synthesize magnesium-doped zinc oxide, silver and gold nanoparticles (Nps) and to evaluate their potential to prevent and eradicate Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa biofilms. Materials & methods: The Nps were synthesized by precipitation and metallic reduction techniques. Physicochemical and biological characterization of Nps was performed. Results: All the Nps tested were able to inhibit the formation of E. coli, P. mirabilis, S. aureus and A. baumannii biofilms. The effects on the eradication of preformed biofilms were variable, although all the Nps tested were able to eradicate A. baumannii biofilms. Conclusion: The observed effects make the Nps suitable for coating surfaces and/or antibiotic carriers with medical interest.


Asunto(s)
Nanopartículas del Metal , Óxido de Zinc , Oro/farmacología , Óxido de Zinc/farmacología , Óxido de Zinc/química , Magnesio/farmacología , Plata/farmacología , Plata/química , Zinc/farmacología , Nanopartículas del Metal/química , Staphylococcus aureus , Óxido de Magnesio/farmacología , Escherichia coli , Biopelículas , Antibacterianos/farmacología , Antibacterianos/química
18.
J Environ Radioact ; 262: 107152, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36933462

RESUMEN

A comprehensive study of the biological effects of chronic radiation exposure (8 µGy/h) in populations of white clover (Trifolium repens L.) from the Chernobyl exclusion zone was carried out. White clover is one of the most important pasture legumes, having many agricultural applications. Studies at two reference and three radioactively contaminated plots showed no stable morphological effects in white clover at this level of radiation exposure. Increased activities of catalase and peroxidases were found in some impacted plots. Auxin concentration was enhanced in the radioactively contaminated plots. Genes involved in the maintenance of water homeostasis and photosynthetic processes (TIP1 and CAB1) were upregulated at radioactively contaminated plots.


Asunto(s)
Accidente Nuclear de Chernóbil , Monitoreo de Radiación , Trifolium , Trifolium/genética , Peroxidasas , Medicago
19.
Int Med Case Rep J ; 16: 135-139, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36925951

RESUMEN

The thoracic cavity contains vital cardiovascular and pulmonary structures. Few congenital anatomical variations in the bronchial tree and pulmonary vasculature have been reported. Understanding such variants is crucial during surgical procedures that involve the thorax. During routine dissection of an 89-year-old male cadaver as part of a first-year anatomy course, an anomaly of the bronchial tree was discovered. The left lung hilum was notable for the pulmonary artery being posterior to the mainstem bronchus. The case report describes normal lung development and anatomy and the significance of this novel variation in which has not been previously described in the literature.

20.
Microorganisms ; 11(2)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36838329

RESUMEN

Lactic acid bacteria (LAB) isolated from healthy humans may prove an effective tool against pathogen growth, adherence and invasion in intestinal epithelial cells. This study aimed to evaluate the antilisterial properties of LAB isolated from fecal samples of healthy neonates. Forty-five LAB strains were tested for their antimicrobial activity against ten Listeria monocytogenes strains with spot-on-lawn and agar-well diffusion assays, and ten lactobacilli strains were further assessed for their inhibitory effect against adherence and invasion of Caco-2 cells by L. monocytogenes EGDe. Inhibition was estimated in competition, exclusion or displacement assays, where lactobacilli and L. monocytogenes were added to Caco-2 monolayers simultaneously or 1 h apart from each other. Inhibition of L. monocytogenes growth was only displayed with the spot-on-lawn assay; cell-free supernatants of lactobacilli were not effective against the pathogen. Lactobacillus (L.) paragasseri LDD-C1 and L. crispatus LCR-A21 were able to adhere to Caco-2 cells at significantly higher levels than the reference strain L. rhamnosus GG. The adherence of L. monocytogenes to Caco-2 cells was reduced by 20.8% to 62.1% and invasion by 33.5% to 63.1% during competition, which was more effective compared to the exclusion and displacement assays. These findings demonstrate that lactobacilli isolated from neonatal feces could be considered a good candidate against L. monocytogenes.

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