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1.
Neurol Res Pract ; 6(1): 25, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693574

RESUMEN

BACKGROUND: Motor and vocal tics are the main symptom of Gilles de la Tourette-syndrome (GTS). A particular complex vocal tic comprises the utterance of swear words, termed coprolalia. Since taboo words are socially inappropriate, they are normally suppressed by people, which implies cognitive control processes. METHOD: To investigate the control of the unintentional pronunciation of taboo words and the associated processes of conflict monitoring, we used the "Spoonerisms of Laboratory Induced Predisposition" (SLIP) paradigm. Participants read multiple inductor word pairs with the same phonemes, followed by pronouncing a target pair with inverse phonemes. This led to a conflict between two competing speech plans: the correct word pair and the word pair with inverted phonemes. Latter speech error, a spoonerism, could result in a neutral or taboo word. We investigated 19 patients with GTS and 23 typically developed controls (TDC) and measured participants' electroencephalography (EEG) during the SLIP task. RESULTS: At the behavioral level less taboo than neutral word spoonerisms occurred in both groups without significant differences. Event-related brain potentials (ERP) revealed a difference between taboo and neutral word conditions in the GTS group at the midline electrodes in a time range of 250-400 ms after the speech prompt, which was not found in the TDC group. The extent of this effect depended on the number of inductor word pairs, suggesting an increasing level of cognitive control in the GTS group. CONCLUSION: The differences between taboo and neutral word conditions in patients with GTS compared to TDC suggest an altered recruitment of cognitive control processes in GTS, likely enlisted to suppress taboo words.

2.
Compr Psychiatry ; 132: 152482, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38603938

RESUMEN

INTRODUCTION: Theoretical frameworks of behavioral addictions mostly acknowledge the role of stress in the development and maintenance of these disorders, models of compulsive buying-shopping disorder (CBSD) however rarely incorporated stress. The association between stress and CBSD has not been reviewed yet. METHODS: A scoping review was conducted to evaluate empirical results on the association between stress and CBSD. A comprehensive search string was employed in three databases. RESULTS: 16 studies were included. Correlative studies suggested significant correlations between general perceived stress and CBSD symptom severity. Studies involving mean comparisons found higher general perceived stress levels in persons with problematic buying-shopping behavior/CBSD compared to control participants (large effects). Mixed results were found in studies involving regression/structural equation models and ecological momentary assessments. One study with a stress/negative mood induction observed more CBSD symptoms in a high stress group compared to a low stress group. DISCUSSION: The studies are heterogeneous concerning design, samples and measures. Only very few studies surpass the level of cross-sectional correlative data which limits the ability to draw clear conclusions. Future research should study the impact of experimentally induced stress on CBSD symptoms, examine the relationship between stress and CBSD longitudinally and assess objective stress markers.


Asunto(s)
Conducta Compulsiva , Estrés Psicológico , Humanos , Estrés Psicológico/psicología , Estrés Psicológico/complicaciones , Conducta Compulsiva/psicología , Conducta Adictiva/psicología
3.
Biotechnol J ; 19(4): e2300505, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38651269

RESUMEN

Chinese hamster ovary (CHO) cells are the commonly used mammalian host system to manufacture recombinant proteins including monoclonal antibodies. However unfavorable non-human glycoprofile displayed on CHO-produced monoclonal antibodies have negative impacts on product quality, pharmacokinetics, and therapeutic efficiency. Glycoengineering such as genetic elimination of genes involved in glycosylation pathway in CHO cells is a viable solution but constrained due to longer timeline and laborious workflow. Here, in this proof-of-concept (PoC) study, we present a novel approach coined CellEDIT to engineer CHO cells by intranuclear delivery of the CRISPR components to single cells using the FluidFM technology. Co-injection of CRISPR system targeting BAX, DHFR, and FUT8 directly into the nucleus of single cells, enabled us to generate triple knockout CHO-K1 cell lines within a short time frame. The proposed technique assures the origin of monoclonality without the requirement of limiting dilution, cell sorting or positive selection. Furthermore, the approach is compatible to develop both single and multiple knockout clones (FUT8, BAX, and DHFR) in CHO cells. Further analyses on single and multiple knockout clones confirmed the targeted genetic disruption and altered protein expression. The knockout CHO-K1 clones showed the persistence of gene editing during the subsequent passages, compatible with serum free chemically defined media and showed equivalent transgene expression like parental clone.


Asunto(s)
Sistemas CRISPR-Cas , Cricetulus , Edición Génica , Células CHO , Animales , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Anticuerpos Monoclonales/genética , Proteínas Recombinantes/genética , Técnicas de Inactivación de Genes/métodos , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Tetrahidrofolato Deshidrogenasa/genética , Tetrahidrofolato Deshidrogenasa/metabolismo , Fucosiltransferasas/genética , Fucosiltransferasas/metabolismo , Cricetinae , Ingeniería Genética/métodos
4.
Cereb Cortex ; 34(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38615240

RESUMEN

The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n > 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.


Asunto(s)
Cafeína , Habituación Psicofisiológica , Humanos , Potenciales Evocados , Electroencefalografía
5.
ACS Nano ; 18(17): 11025-11041, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38626916

RESUMEN

ALK-positive NSCLC patients demonstrate initial responses to ALK tyrosine kinase inhibitor (TKI) treatments, but eventually develop resistance, causing rapid tumor relapse and poor survival rates. Growing evidence suggests that the combination of drug and immune therapies greatly improves patient survival; however, due to the low immunogenicity of the tumors, ALK-positive patients do not respond to currently available immunotherapies. Tumor-associated macrophages (TAMs) play a crucial role in facilitating lung cancer growth by suppressing tumoricidal immune activation and absorbing chemotherapeutics. However, they can also be programmed toward a pro-inflammatory tumor suppressive phenotype, which represents a highly active area of therapy development. Iron loading of TAMs can achieve such reprogramming correlating with an improved prognosis in lung cancer patients. We previously showed that superparamagnetic iron oxide nanoparticles containing core-cross-linked polymer micelles (SPION-CCPMs) target macrophages and stimulate pro-inflammatory activation. Here, we show that SPION-CCPMs stimulate TAMs to secrete reactive nitrogen species and cytokines that exert tumoricidal activity. We further show that SPION-CCPMs reshape the immunosuppressive Eml4-Alk lung tumor microenvironment (TME) toward a cytotoxic profile hallmarked by the recruitment of CD8+ T cells, suggesting a multifactorial benefit of SPION-CCPM application. When intratracheally instilled into lung cancer-bearing mice, SPION-CCPMs delay tumor growth and, after first line therapy with a TKI, halt the regrowth of relapsing tumors. These findings identify SPIONs-CCPMs as an adjuvant therapy, which remodels the TME, resulting in a delay in the appearance of resistant tumors.


Asunto(s)
Crizotinib , Neoplasias Pulmonares , Nanopartículas Magnéticas de Óxido de Hierro , Microambiente Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Microambiente Tumoral/efectos de los fármacos , Animales , Nanopartículas Magnéticas de Óxido de Hierro/química , Humanos , Ratones , Crizotinib/farmacología , Crizotinib/química , Antineoplásicos/farmacología , Antineoplásicos/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Línea Celular Tumoral , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Proliferación Celular/efectos de los fármacos , Femenino
6.
World Neurosurg ; 185: 393-402.e27, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38437980

RESUMEN

BACKGROUND: Despite the ubiquitous use of the Glasgow Coma Scale (GCS) worldwide, no study to date has objectively and quantitatively assessed its impact on the scientific literature and clinical practice. Therefore, we comprehensively analyzed scientific publications and clinical practice guidelines employing the GCS to gauge its clinical and academic impact, identify research hotspots, and inform future research on the topic. METHODS: A cross-sectional bibliometric analysis was performed on Scopus to obtain relevant publications incorporating the GCS from 1974 to 2022. In addition, a systematic review of existing clinical practice guidelines in PubMed, Scopus, Web of Science, and Trip Database was performed. Validated bibliometric parameters including article title, journal, publication year, authors, citation count, country, institution, keywords, impact factor, and references were assessed. When evaluating clinical practice guidelines, the sponsoring organization, country of origin, specialty, and publication year were assessed. RESULTS: A total of 37,633 articles originating from 3924 different scientific journals spanning 1974-2022 were included in the final analysis. The compound annual growth rate of publications referencing the GCS was 16.7%. Of 104 countries, the United States had the highest total number of publications employing the GCS (n = 8517). World Neurosurgery was the scientific periodical with the highest number of publications on the GCS (n = 798). The top trending author-supplied keyword was "traumatic brain injury" (n = 3408). The 97 included clinical practice guidelines most commonly employed the GCS in the fields of internal medicine (n = 22, 23%), critical care (n = 21, 22%), and neurotrauma (n = 19, 20%). CONCLUSIONS: At the turn of the 50th anniversary of the GCS, we provided a unique and detailed description of the "path to success" of the GCS both in terms of its scientific and clinical impact. These results have not only a historical but also an important didactic value. Ultimately our detailed analysis, which revealed some of the factors that led the GCS to become such a widespread and highly influential score, may assist future researchers in their development of new outcome measures and clinical scores, especially as such tools become increasingly relevant in an evidence-based data-driven age.


Asunto(s)
Bibliometría , Escala de Coma de Glasgow , Guías de Práctica Clínica como Asunto , Humanos , Estudios Transversales
7.
Commun Chem ; 7(1): 39, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38402292

RESUMEN

The sorbicillinoid family is a large class of natural products known for their structural variety and strong, diverse biological activities. A special member of this family, sorbicillactone A, the first nitrogen-containing sorbicillinoid, exhibits potent anti-leukemic and anti-HIV activities and possesses a unique structure formed from sorbicillinol, alanine, and fumaric acid building blocks. To facilitate in-depth biological and structure-activity relationship studies of this promising natural product, we developed a chemoenzymatic approach that provides access to sorbicillactone A and several analogs with excellent yields under precise stereochemical control. The key steps of the highly convergent, stereoselective, and short route are the enantioselective oxidative dearomatization of sorbillin to sorbicillinol catalyzed by the enzyme SorbC and the subsequent Michael addition of a fumarylazlactone building block. Additionally, our synthetic findings and bioinformatic analysis suggest that sorbicillactone A is biosynthetically formed analogously.

8.
Chemistry ; 30(21): e202400105, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38299788

RESUMEN

Partial ligand substitution at the iron pentacarbonyl radical cation generates novel half-sandwich complexes of the type [Fe(η6-arene)(CO)2]⋅+ (arene=1,3,5-tri-tert-butylbenzene, 1,3,5-trimethylbenzene, benzene and fluorobenzene). Of those, the bulkier 1,3,5-tri-tert-butylbenzene (mes*) derivative [Fe(mes*)(CO)2]⋅+ was fully characterized by XRD analysis, IR, NMR, cw-EPR, Mössbauer spectroscopy and cyclic voltammetry as the [Al(ORF)4]- (RF=C(CF3)3) salt. Chemical electronation, i. e., the single electron reduction, with decamethylferrocene generates neutral [Fe(mes*)(CO)2], whereas further deelectronation under CO-pressure leads to a dicationic three-legged [Fe(mes*)(CO)3]2+ salt with [Al(ORF)4]- counterion. The full substitution of the carbonyl ligands in [Fe(CO)5]⋅+[Al(ORF)4]- mainly resulted in disproportionation reactions, giving solid Fe(0) and the dicationic bis-arene salts [Fe(η6-arene)2]2+([Al(ORF)4]-)2 (arene=1,3,5-trimethylbenzene, benzene and fluorobenzene). Only by employing the very large fluoride bridged anion [F-{Al(ORF)3}2]-, it was possible to isolate an open shell bis-arene cation salt [Fe(C6H6)2]⋅+[F-{Al(ORF)3}2]-. The highly reactive cation was characterized by XRD analysis, cw-EPR, Mössbauer spectroscopy and cyclic voltammetry. The disproportionation of [Fe(C6H6)2]⋅+ salts to give solid Fe(0) and [Fe(C6H6)2]2+ salts was analyzed by a suitable cycle, revealing that the thermodynamic driving force for the disproportionation is a function of the size of the anion used and the polarity of the solvent.

9.
Science ; 383(6690): eabn3263, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38422184

RESUMEN

Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.


Asunto(s)
Elementos de Facilitación Genéticos , Euterios , Evolución Molecular , Regulación de la Expresión Génica , Corteza Motora , Neuronas Motoras , Proteínas , Vocalización Animal , Animales , Quirópteros/genética , Quirópteros/fisiología , Vocalización Animal/fisiología , Corteza Motora/citología , Corteza Motora/fisiología , Cromatina/metabolismo , Neuronas Motoras/fisiología , Laringe/fisiología , Epigénesis Genética , Genoma , Proteínas/genética , Proteínas/metabolismo , Secuencia de Aminoácidos , Euterios/genética , Euterios/fisiología , Aprendizaje Automático
10.
Artículo en Inglés | MEDLINE | ID: mdl-38366232

RESUMEN

BACKGROUND: While prognosis of acute myocarditis with uncomplicated presentation is perceived as benign, data on long-term outcomes is scarce. We evaluated rates of myocarditis-associated cardiovascular events after a first-time hospitalization with uncomplicated acute myocarditis in patients without known heart disease. METHODS: In this retrospective nationwide population-based cohort study from 2013 to 2020, hospitalized patients with uncomplicated acute myocarditis but without known heart disease were 1:1 propensity score-matched with surgical controls hospitalized for laparoscopic appendectomy. As assessed in time-to-event analyses, the primary outcome was a composite of rehospitalization for myocarditis, pericardial disease, heart failure and its complications, arrhythmias, implantation of cardiac devices, and heart transplant. RESULTS: After matching, we identified 1,439 patients with uncomplicated acute myocarditis (median age of 35 years, 74.0% male) and 1,439 surgical controls (median age of 36 years, 74.4% male). Over a median follow-up of 39 months, compared with surgical controls, the hazard ratio (HR) for the primary composite outcome was 42.3 (95% confidence interval [CI], 17.4 to 102.8), corresponding to an incidence rate (IR) of 43.7 vs. 0.9 per 1,000 patient-years (py) and an incidence rate difference (IRD) of 42.7 (95% CI, 36.7 to 48.8) per 1,000 py. CONCLUSION: Patients hospitalized with uncomplicated acute myocarditis and no known prior heart disease were associated with substantial risk for cardiovascular events over a follow-up of up to 8 years. This calls for a more efficient therapeutic management of this population of patients.

11.
Environ Res ; 246: 118123, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38185220

RESUMEN

Shorebirds (order Charadriiformes) are among the world's most threatened avian taxa. Within the East Asian-Australasian Flyway (EAAF), a major threat to shorebirds' survival may be the gauntlet of pollution along the flyway. Metals, persistent organic pollutants (POPs), and per-/polyfluoroalkyl substances (PFASs) persist in the environment to the detriment of wildlife. In this study, we analysed element and PFAS concentrations in blood from 142 individuals across six species of Arctic-breeding migratory shorebirds with contrasting population trends, to discern species- and site-specific pollution differences, and determine how pollution correlated with population trends of EAAF shorebirds. Potential within-year pollution variations were investigated by blood-sampling birds at two sites, representing different points in the birds' annual migrations: staging in Taiwan on southward migrations and at non-breeding grounds in Western Australia (WA). Species' pollutant concentrations were compared to established population trends. Concentrations of potentially toxic elements were low in most individuals regardless of species. PFASs (range: <0.001-141 ng/g), Hg (<0.001-9910 ng/g) and Pb (<0.01-1210 ng/g) were higher in Taiwan than in WA (PFAS Taiwan median: 14.5 ng/g, WA median: 3.45 ng/g; Hg Taiwan: 338 ng/g, WA: 23.4 ng/g; Pb Taiwan: 36.8 ng/g, WA: 2.26 ng/g). Meanwhile As (range <0.001-8840 ng/g) and Se (290-47600 ng/g) were higher in WA than Taiwan (As Taiwan median: 500 ng/g, WA median: 1660 ng/g; Se Taiwan: 5490 ng/g, Se WA: 23700 ng/g). Nevertheless, pollutant concentrations in a subset of individuals may exceed sublethal effect thresholds (As, Se and PFASs). Finally, we found no consistent differences in pollution among species and demonstrated no correlation between pollution and population trends, suggesting pollution is likely not a major driver for population declines of EAAF shorebirds. However, ongoing and locally heavy environmental degradation and exposure to other contaminants not investigated here, such as POPs, warrants continued consideration when managing EAAF shorebird populations.


Asunto(s)
Contaminantes Ambientales , Fluorocarburos , Mercurio , Humanos , Animales , Contaminantes Ambientales/análisis , Plomo , Aves , Mercurio/análisis , Fluorocarburos/análisis
12.
Bone Marrow Transplant ; 59(3): 380-386, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38184740

RESUMEN

Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Nitrilos , Fotoféresis , Pirazoles , Pirimidinas , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Esteroides/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Fotoféresis/métodos , Enfermedad Crónica , Trasplante de Células Madre Hematopoyéticas/efectos adversos
14.
Langmuir ; 40(5): 2487-2499, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38180486

RESUMEN

The solvophobicity-driven directional self-assembly of polymer-coated gold nanorods is a well-established phenomenon. Yet, the kinetics of this process, the origin of site-selectivity in the self-assembly, and the interplay of (attractive) solvophobic brush interactions and (repulsive) electrostatic forces are not fully understood. Herein, we use a combination of time-resolved (vis/NIR) extinction spectroscopy and finite-difference time-domain (FDTD) simulations to determine conversion profiles for the assembly of gold nanorods with polystyrene shells of distinct thicknesses into their (tip-to-tip) self-assembled structures. In particular, we demonstrate that the assembly process is highly protracted compared with diffusion-controlled rates, and we find that the assembly rate varies for different thickness values of the polymer shell. Our findings were rationalized using coarse-grained molecular dynamics simulations, which also corroborated the tip-to-tip preference in the self-assembly process, albeit with a uniform polymer coating. Utilizing the knowledge of quantified conversion rates for distinct colloidal species, we designed coassembling systems with different brush thicknesses, featuring "narcissistic" self-sorting behavior. This provides new perspectives for high-level supracolloidal self-assembly.

15.
Nanoscale ; 15(46): 18687-18695, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-37941432

RESUMEN

We achieved external activation of local hot-spot sites in supracolloidal assembly structures. The concept was demonstrated by boosting surface-enhanced Raman scattering (SERS) efficiency by one order of magnitude through a heating-induced process. Our approach involves assembling gold nanoparticles with distinct dimensions, i.e. 16 and 80 nm, into well-defined planet-satellite-type arrangement structures using thermoresponsive (poly(N-isopropylacrylamide)) star polymer linkers. Insights into the assembly process were obtained by calculations within the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory framework. We observe one order of magnitude increase in SERS enhancement by a heating-induced volume-phase transition. This magnification aligns with simulations run using the finite-difference time-domain (FDTD) method. The implications of this adaptive supracolloidal concept are twofold: Firstly, our approach bypasses limitations of existing systems that are associated with the limited accessibility of electromagnetic hot-spot sites in strongly coupled, static assemblies of plasmonic nanoparticles, by providing the capability of dynamic hot-spot re-configuration. Second, these externally activated probes offer promising opportunities for the development of messenger materials and associated sensing strategies.

16.
N Am Spine Soc J ; 16: 100281, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37942311

RESUMEN

Background: Traumatic pneumocephalus (TPC) following craniofacial injuries is common, but isolated TPC secondary to pneumorrhachis (PR) is the rare result of upward gas migration from the spinal canal. In the absence of craniofacial and grossly unstable spinal fractures, the etiology of TPC in polytrauma can be elusive and an underlying diagnosis of acute spinal cord injury (SCI) can be easily missed. We report the first polytrauma case where TPC was the most reliable early sign of SCI. Case Description: A 34-year-old polytrauma female with imaging findings of TPC, which was later found to be secondary to an underlying SCI. As a focused exam could not be performed at admission, the TPC was first attributed to undiagnosed craniofacial injuries. Tertiary survey revealed the patient being paraplegic and MRI workup demonstrated an acute SCI at the T3-T4 level. PR was the most likely cause of TPC in the absence of other craniofacial injuries. Outcome: The patient did not have a meaningful recovery given the extensive hemispheric infarcts, spinal cord injury, and respiratory failure. Conclusions: Although uncommon, TPC may be an important radiographic sign suggesting the possibility of an underlying SCI in polytrauma patients. especially when focused neurologic assessment is limited at admission. Polytrauma patients with TPC and PR in the absence of coexisting craniofacial fractures require an urgent spine consultation by the ER physician, with possible early spine MRI workup. We suggest a diagnostic algorithm for the early identification of SCI in polytrauma patients presenting with TPC and propose considering 3 groups which may have different risks for SCI based on their clinical presentation and the presence of PR.

18.
iScience ; 26(12): 108289, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38034352

RESUMEN

Peritoneal adhesions are poorly understood but highly prevalent conditions that can cause intestinal obstruction and pelvic pain requiring surgery. While there is consensus that stress-induced inflammation triggers peritoneal adhesions, the molecular processes of their formation still remain elusive. We performed murine models and analyzed human samples to monitor the formation of adhesions and the treatment with DNases. Various molecular analyses were used to evaluate the adhesions. The experimental peritoneal adhesions of the murine models and biopsy material from humans are largely based on neutrophil extracellular traps (NETs). Treatment with DNASE1 (Dornase alfa) and the human DNASE1L3 analog (NTR-10), significantly reduced peritoneal adhesions in experimental models. We conclude that NETs serve as essential scaffold for the formation of adhesions; DNases interfere with this process. Herein, we show that therapeutic application of DNases can be employed to prevent the formation of murine peritoneal adhesions. If this can be translated into the human situation requires clinical studies.

19.
Viruses ; 15(11)2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-38005838

RESUMEN

Human immunodeficiency virus type 2 (HIV-2) is known to be less pathogenic than HIV-1. However, the mechanism(s) underlying the decreased HIV-2 pathogenicity is not fully understood. Herein, we report that ß-chemokine CCL2 expression was increased in HIV-1-infected human monocyte-derived macrophages (MDM) but decreased in HIV-2-infected MDM when compared to uninfected MDM. Inhibition of CCL2 expression following HIV-2 infection occurred at both protein and mRNA levels. By microarray analysis, quantitative PCR, and Western blotting, we identified that Signal Transducer and Activator of Transcription 1 (STAT1), a critical transcription factor for inducing CCL2 gene expression, was also reduced in HIV-2-infected MDM. Blockade of STAT1 in HIV-infected MDM using a STAT1 inhibitor significantly reduced the production of CCL2. In contrast, transduction of STAT1-expressing pseudo-retrovirus restored CCL2 production in HIV-2-infected MDM. These findings support the concept that CCL2 inhibition in HIV-2-infected MDM is meditated by reduction of STAT1. Furthermore, we showed that STAT1 reduction in HIV-2-infected MDM was regulated by the CUL2/RBX1 ubiquitin E3 ligase complex-dependent proteasome pathway. Knockdown of CUL2 or RBX1 restored the expression of STAT1 and CCL2 in HIV-2-infected MDM. Taken together, our findings suggest that differential regulation of the STAT1-CCL2 axis may be one of the mechanisms underlying the different pathogenicity observed for HIV-1 and HIV-2.


Asunto(s)
Quimiocina CCL2 , Infecciones por VIH , VIH-1 , VIH-2 , Humanos , Células Cultivadas , Regulación de la Expresión Génica , Seropositividad para VIH , VIH-1/genética , VIH-2/genética , Macrófagos , Virulencia , Replicación Viral , Quimiocina CCL2/metabolismo , Infecciones por VIH/metabolismo , Infecciones por VIH/virología
20.
Hipertens Riesgo Vasc ; 40(3): 119-125, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37748946

RESUMEN

BACKGROUND AND METHODOLOGY: Air pollutants have a significant impact on public health. The aim of the study was to find out the relationship between ambulatory blood pressure measured by 24-h ambulatory blood pressure monitoring (ABPM) and the atmospheric pollutants that are measured regularly (PM10, PM2.5, NO2 and SO2). An observational study of temporal and geographic measurements of individual patients (case-time series design) was carried out in Primary Care Centres and Hypertension Units in the Barcelona metropolitan area. We included 2888 hypertensive patients≥18 years old, untreated, with a first valid ABPM performed between 2005 and 2014 and with at least one air pollution station within a radius of <3km. RESULTS AND CONCLUSIONS: The mean age was 54.3 (SD 14.6) years. 50.1% were women and 16.9% of the sample were smokers. Mean 24-h blood pressure (BP) was 128.0 (12.7)/77.4 (9.7) mmHg. After adjusting for mean ambient temperature and different risk factors, a significant association was found between ambulatory diastolic BP (DBP) and PM10 concentrations the day before ABPM. For each increase of 10µg/m3 of PM10, an increase of 1.37mmHg 24-h DBP and 1.48mmHg daytime DBP was observed. No relationship was found between PM2.5, NO2 and SO2 and ambulatory BP, nor between any pollutant and clinical BP. The concentration of PM10 the day before the ABPM is significantly associated with an increase in 24-h DBP and daytime DBP.

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