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1.
J Neurosci ; 43(18): 3331-3338, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-37012054

RESUMEN

The bed nucleus of the stria terminalis (BNST) has been implicated in a variety of social behaviors, including aggression, maternal care, mating behavior, and social interaction. Limited evidence from rodent studies suggests that activation of the BNST results in a decrease in social interaction between unfamiliar animals. The role of the BNST in social interaction in primates remains wholly unexamined. Nonhuman primates provide a valuable model for studying social behavior because of both their rich social repertoire and neural substrates of behavior with high translational relevance to humans. To test the hypothesis that the primate BNST is a critical modulator of social behavior, we performed intracerebral microinfusions of the GABAA agonist muscimol to transiently inactivate the BNST in male macaque monkeys. We measured changes in social interaction with a familiar same-sex conspecific. Inactivation of the BNST resulted in significant increase in total social contact. This effect was associated with an increase in passive contact and a significant decrease in locomotion. Other nonsocial behaviors (sitting passively alone, self-directed behaviors, and manipulation) were not impacted by BNST inactivation. As part of the "extended amygdala," the BNST is highly interconnected with the basolateral (BLA) and central (CeA) nuclei of the amygdala, both of which also play critical roles in regulating social interaction. The precise pattern of behavioral changes we observed following inactivation of the BNST partially overlaps with our prior reports in the BLA and CeA. Together, these data demonstrate that the BNST is part of a network regulating social behavior in primates.SIGNIFICANCE STATEMENT The bed nucleus of the stria terminalis (BNST) has a well-established role in anxiety behaviors, but its role in social behavior is poorly understood. No prior studies have evaluated the impact of BNST manipulations on social behavior in primates. We found that transient pharmacological inactivation of the BNST increased social behavior in pairs of macaque monkeys. These data suggest the BNST contributes to the brain networks regulating sociability.


Asunto(s)
Núcleos Septales , Humanos , Animales , Masculino , Macaca mulatta , Núcleos Septales/fisiología , Conducta Social , Amígdala del Cerebelo/fisiología , Agresión
2.
Brain ; 146(10): 4320-4335, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37192344

RESUMEN

While anti-seizure medications are effective for many patients, nearly one-third of individuals have seizures that are refractory to pharmacotherapy. Prior studies using evoked preclinical seizure models have shown that pharmacological activation or excitatory optogenetic stimulation of the deep and intermediate layers of the superior colliculus (DLSC) display multi-potent anti-seizure effects. Here we monitored and modulated DLSC activity to suppress spontaneous seizures in the WAG/Rij genetic model of absence epilepsy. Female and male WAG/Rij adult rats were employed as study subjects. For electrophysiology studies, we recorded single unit activity from microwire arrays placed within the DLSC. For optogenetic experiments, animals were injected with virus coding for channelrhodopsin-2 or a control vector, and we compared the efficacy of continuous neuromodulation to that of closed-loop neuromodulation paradigms. For each, we compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). For closed-loop stimulation, we detected seizures in real time based on the EEG power within the characteristic frequency band of spike-and-wave discharges (SWDs). We quantified the number and duration of each SWD during each 2 h-observation period. Following completion of the experiment, virus expression and fibre-optic placement was confirmed. We found that single-unit activity within the DLSC decreased seconds prior to SWD onset and increased during and after seizures. Nearly 40% of neurons displayed suppression of firing in response to the start of SWDs. Continuous optogenetic stimulation of the DLSC (at each of the three frequencies) resulted in a significant reduction of SWDs in males and was without effect in females. In contrast, closed-loop neuromodulation was effective in both females and males at all three frequencies. These data demonstrate that activity within the DLSC is suppressed prior to SWD onset, increases at SWD onset, and that excitatory optogenetic stimulation of the DLSC exerts anti-seizure effects against absence seizures. The striking difference between open- and closed-loop neuromodulation approaches underscores the importance of the stimulation paradigm in determining therapeutic effects.


Asunto(s)
Epilepsia Tipo Ausencia , Ratas , Masculino , Humanos , Animales , Femenino , Epilepsia Tipo Ausencia/genética , Epilepsia Tipo Ausencia/terapia , Colículos Superiores , Optogenética/métodos , Convulsiones/terapia , Electroencefalografía , Modelos Animales de Enfermedad
3.
Eur J Public Health ; 34(1): 44-51, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37875008

RESUMEN

BACKGROUND: Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. METHODS: In the VOICE community-a European healthcare centre cluster intending to address VBHC from theory to practice-information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. RESULTS: Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. CONCLUSIONS: To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions.


Asunto(s)
Benchmarking , Calidad de la Atención de Salud , Humanos , Benchmarking/métodos , Atención a la Salud
4.
Eur Arch Otorhinolaryngol ; 281(6): 3253-3259, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38436756

RESUMEN

PURPOSE: ChatGPT (Chat-Generative Pre-trained Transformer) has proven to be a powerful information tool on various topics, including healthcare. This system is based on information obtained on the Internet, but this information is not always reliable. Currently, few studies analyze the validity of these responses in rhinology. Our work aims to assess the quality and reliability of the information provided by AI regarding the main rhinological pathologies. METHODS: We asked to the default ChatGPT version (GPT-3.5) 65 questions about the most prevalent pathologies in rhinology. The focus was learning about the causes, risk factors, treatments, prognosis, and outcomes. We use the Discern questionnaire and a hexagonal radar schema to evaluate the quality of the information. We use Fleiss's kappa statistical analysis to determine the consistency of agreement between different observers. RESULTS: The overall evaluation of the Discern questionnaire resulted in a score of 4.05 (± 0.6). The results in the Reliability section are worse, with an average score of 3.18. (± 1.77). This score is affected by the responses to questions about the source of the information provided. The average score for the Quality section was 3.59 (± 1.18). Fleiss's Kappa shows substantial agreement, with a K of 0.69 (p < 0.001). CONCLUSION: The ChatGPT answers are accurate and reliable. It generates a simple and understandable description of the pathology for the patient's benefit. Our team considers that ChatGPT could be a useful tool to provide information under prior supervision by a health professional.


Asunto(s)
Otolaringología , Humanos , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Internet , Enfermedades Nasales/diagnóstico
5.
Int J Mol Sci ; 25(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38928373

RESUMEN

Cytokinesis in plant cells begins with the fusion of vesicles that transport cell wall materials to the center of the cell division plane, where the cell plate forms and expands radially until it fuses with the parental cell wall. Vesicle fusion is facilitated by trans-SNARE complexes, with assistance from Sec1/Munc18 (SM) proteins. The SNARE protein KNOLLE and the SM protein KEULE are required for membrane fusion at the cell plate. Due to the crucial function of KEULE, all Arabidopsis (Arabidopsis thaliana) keule mutants identified to date are seedling lethal. Here, we identified the Arabidopsis serrata4-1 (sea4-1) and sea4-2 mutants, which carry recessive, hypomorphic alleles of KEULE. Homozygous sea4-1 and sea4-2 plants are viable and fertile but have smaller rosettes and fewer leaves at bolting than the wild type. Their leaves are serrated, small, and wavy, with a complex venation pattern. The mutant leaves also develop necrotic patches and undergo premature senescence. RNA-seq revealed transcriptome changes likely leading to reduced cell wall integrity and an increase in the unfolded protein response. These findings shed light on the roles of KEULE in postembryonic development, particularly in the patterning of rosette leaves and leaf margins.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Mutación , Hojas de la Planta , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Pared Celular/metabolismo , Pared Celular/genética , Fenotipo
6.
Alcohol Alcohol ; 58(5): 515-522, 2023 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36760095

RESUMEN

BACKGROUND: The number of inpatients with alcohol and other substance-related problems (ASRP) in the general hospital population at any time is vast. To meet the needs of those patients, most hospitals have an Addiction Liaison Team (ALT) that diagnoses and initiates the treatment of the addictive disorder. In our hospital, this team is part of a more extensive and intensive Outpatient Alcoholism Treatment Programme that facilitates the continuity of care. AIM: the main goal of this study is to evaluate the performance and effectiveness of our inpatient ALT. METHODOLOGY: we carried out an observational cohort study of patients with ASRP admitted to the hospital from 2015 to 2017. We evaluated the performance and effectiveness of our ALT: referrals to the programme, inpatients mortality, readmissions to hospital, hospital length of stay (LOS) and medical or surgical treatment adherence. RESULTS: out of 133,181 admissions, 17,387 (13.14%) were positive for ASRP, and 615 (3.54%) were referred to the ALT. Referred patients had less in-hospital mortality, shorter LOS and lower risk of readmissions during the first year of follow-up. Subjects treated in the programme had better therapeutic adherence. CONCLUSIONS: integrating the ALT into an outpatient programme facilitates an earlier detection and initiation of treatment during the hospital stay and the continuity of care. Alcohol misuse conditions affect the patient's prognosis and health outcomes, so appropriate care is needed. Inclusion in the programme was associated with less risk of hospital mortality, fewer readmissions and a lower LOS.


Asunto(s)
Alcoholismo , Humanos , Estudios Retrospectivos , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Alcoholismo/terapia , Pacientes Ambulatorios , Hospitalización , Tiempo de Internación
7.
J Anim Physiol Anim Nutr (Berl) ; 107(1): 62-76, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35253270

RESUMEN

Probiotics are live microorganisms that confer health benefits to their animal host by balancing the composition of its gastrointestinal microbiota and modulating its immune response. In this work, we studied bacterial consortia isolated from the rumen of 28- and 42-day-old calves to select those showing probiotic capacity. Consortia were characterized and their growth dynamics were determined in several growth media. The number of viable bacteria was larger in the Man, Rogosa and Sharpe broth (MRS) than in nutritive medium A (MNA) and the largest was for A3D42. Antibiotic susceptibility of bacterial consortia in MRS was higher than in MNA and the most susceptible samples were A1D28 and A3D42. In turn, A3D42 showed the highest tolerance to bile salts in MRS and MNA. Moreover, all bacterial consortia showed optimal growth at pH 5, 5.5, 6 and 7 in both media, while their temperature tolerance was higher in MRS. The antagonistic activity of bacterial consortia in MNA was higher than in MRS with A2D42 showing the best antagonistic activity for Pseudomona aureginosa (ATCC 9027) and Staphylococcus aureus (ATCC 6538) in MNA. Additionally, A1D42 and A2D42 in MRS and A3D42 in MNA had significant adhesion to mucins, and A1D42 in MRS had the highest. Regarding their species composition, all bacterial consortia in MRS belonged to the phylum Firmicutes, and the class Bacilli and bacterial consortia in MNA belonged to three phyla; Proteobacteria, Firmicutes, and Bacteroidetes. Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus johnsonii were identified in all bacterial consortia in MRS broth. Based on these results, A1D42 and A3D42 grown in MRS showed the best potential as probiotics for calves, which could result in health benefits and improve their production.


Asunto(s)
Lacticaseibacillus casei , Lacticaseibacillus rhamnosus , Probióticos , Animales , Bovinos , Rumen , Probióticos/farmacología
8.
BMC Oral Health ; 23(1): 485, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-37452399

RESUMEN

BACKGROUND: Establishing the level of surgical difficulty pre-operatively is an essential step in ensuring correct treatment planning. This study set out to determine whether the knowledge and experience acquired by dentists who had received different levels of training influenced, firstly, the perceived levels of difficulty of a variety of cases of mandibular third molar (MTM) extraction and, secondly, the perceived difficulty deriving from a series of factors (patient-related factors, anatomical and radiographic factors, operative factors). METHODS: This cross-sectional, descriptive, observational study took the form of a survey. Using a visual analog scale (VAS), participants evaluated both the perceived difficulty of 30 cases of MTM extraction described by means of digital panoramic radiographs and the perceived difficulty deriving from a series of factors conditioning MTM extraction. The results underwent statistical analysis with SPSS Statistics 28.0 software. Non-parametric tests (Mann Whitney test for independent samples and the Kruskal-Wallis test) were applied. RESULTS: A total of 389 surveys were available for analysis. Dental practioners with no surgical training saw the intervention as presenting greater difficulty. Professionals with postgraduate training in oral surgery considered patient-related factors more important than operative factors, in contrast to dentists who had not received oral surgery training. CONCLUSIONS: Dental training has a signficant influence on the perceived difficulty of MTM extraction and also affects opinions about which factors have greater or lesser influence on surgical difficulty.


Asunto(s)
Tercer Molar , Diente Impactado , Humanos , Tercer Molar/diagnóstico por imagen , Tercer Molar/cirugía , Estudios Transversales , Extracción Dental/métodos , Encuestas y Cuestionarios , Proyectos de Investigación , Mandíbula/cirugía , Diente Impactado/cirugía
9.
PLoS Pathog ; 16(2): e1008320, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32078661

RESUMEN

Fungal parasitism depends on the ability to invade host organisms and mandates adaptive cell wall remodeling to avoid detection and defense reactions by the host. All plant and human pathogens share invasive strategies, which aid to escape the chitin-triggered and chitin-targeted host immune system. Here we describe the full spectrum of the chitin/chitosan-modifying enzymes in the mycoparasite Trichoderma atroviride with a central role in cell wall remodeling. Rapid adaption to a variety of growth conditions, environmental stresses and host defense mechanisms such as oxidative stress depend on the concerted interplay of these enzymes and, ultimately, are necessary for the success of the mycoparasitic attack. To our knowledge, we provide the first in class description of chitin and associated glycopolymer synthesis in a mycoparasite and demonstrate that they are essential for biocontrol. Eight chitin synthases, six chitin deacetylases, additional chitinolytic enzymes, including six chitosanases, transglycosylases as well as accessory proteins are involved in this intricately regulated process. Systematic and biochemical classification, phenotypic characterization and mycoparasitic confrontation assays emphasize the importance of chitin and chitosan assembly in vegetative development and biocontrol in T. atroviride. Our findings critically contribute to understanding the molecular mechanism of chitin synthesis in filamentous fungi and mycoparasites with the overarching goal to selectively exploit the discovered biocontrol strategies.


Asunto(s)
Quitina/metabolismo , Quitosano/metabolismo , Trichoderma/metabolismo , Pared Celular/metabolismo , Quitina/fisiología , Quitina Sintasa/metabolismo , Regulación Fúngica de la Expresión Génica/genética , Glicósido Hidrolasas , Filogenia , Plantas/metabolismo , Trichoderma/crecimiento & desarrollo , Trichoderma/patogenicidad
10.
Microb Pathog ; 170: 105718, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35961485

RESUMEN

Scedosporium apiospermum is an opportunistic pathogen that can cause pulmonary infections in both immunosuppressive and immunocompetent patients. Cytokines are molecules that mediate the immune response to promote or eliminate fungal infections. In this work, we evaluated the cytokines profile in the lung and serum of mice infected with Scedosporium apiospermum. We found early production of IL-6, IL-1ß and TNF-α cytokines in the lung of infected mice during the first 5 days of infection. We suggest that release of pro-inflammatory cytokines could play a role in the control of fungal invasion.


Asunto(s)
Micosis , Neumonía , Scedosporium , Animales , Antifúngicos/uso terapéutico , Citocinas , Pulmón , Ratones , Micosis/tratamiento farmacológico , Neumonía/tratamiento farmacológico
11.
Proc Natl Acad Sci U S A ; 116(52): 27084-27094, 2019 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-31843937

RESUMEN

Three decades of studies have shown that inhibition of the substantia nigra pars reticulata (SNpr) attenuates seizures, yet the circuits mediating this effect remain obscure. SNpr projects to the deep and intermediate layers of the superior colliculus (DLSC) and the pedunculopontine nucleus (PPN), but the contributions of these projections are unknown. To address this gap, we optogenetically silenced cell bodies within SNpr, nigrotectal terminals within DLSC, and nigrotegmental terminals within PPN. Inhibition of cell bodies in SNpr suppressed generalized seizures evoked by pentylenetetrazole (PTZ), partial seizures evoked from the forebrain, absence seizures evoked by gamma-butyrolactone (GBL), and audiogenic seizures in genetically epilepsy-prone rats. Strikingly, these effects were fully recapitulated by silencing nigrotectal projections. By contrast, silencing nigrotegmental terminals reduced only absence seizures and exacerbated seizures evoked by PTZ. These data underscore the broad-spectrum anticonvulsant efficacy of this circuit, and demonstrate that specific efferent projection pathways differentially control different seizure types.

12.
Pharm Res ; 38(12): 2047-2063, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34932170

RESUMEN

PURPOSE: Both inter-individual (IIV) and inter-occasion (IOV) variabilities are observed in bioequivalence studies. High IOV may be a cause of problems on the demonstration of bioequivalence, despite strict measures are taken to control it. The objective of this study is to investigate further means of controlling IIV by optimizing study design of crossover studies. METHODS: Data from 18 bioequivalence studies were used to develop population pharmacokinetics (popPK) models to characterize the absorption and disposition processes of 14 drugs, to estimate IOV for each drug substance and to evaluate possible correlations with biopharmaceutical properties of drug substances, classified in accordance to the Biopharmaceutics Drug Disposition Classification System (BDDCS). RESULTS: Plasma-pharmacokinetics profiles for the 14 drugs analyzed were successfully described using popPK. The pharmacokinetic parameters that showed greater variability were first-order rate constant of absorption, duration of the zero-order absorption process, relative bioavailability and time of latency. ISCV% estimated for Cmax seems to correlate with the log-Dose-Number for Class 1, 2 and 3, despite no direct correlation was observed between popPK model residual variability (RUV) and ISCV%. Nevertheless, higher RUV estimates were observed for Class 2 drugs in comparison to Class 1 and 3. CONCLUSION: Pharmacokinetic parameters related to drug absorption showed greater variability. Ingestion of the IMP along with 240 mL of water showed to standardize gastric emptying. Given the dependency between Cmax variability and dose-solubility ratio, for classes 2 and 4, ad libitum water intake may increase Cmax and AUC ISCV%. A water ingestion standardization until the expected Tmax of the drug is suggested.


Asunto(s)
Absorción Gastrointestinal , Modelos Biológicos , Administración Oral , Disponibilidad Biológica , Variación Biológica Individual , Variación Biológica Poblacional , Biofarmacia , Ensayos Clínicos como Asunto , Estudios Cruzados , Humanos , Solubilidad , Equivalencia Terapéutica , Distribución Tisular
13.
Molecules ; 26(9)2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-34063077

RESUMEN

Pollution due to acidic and metal-enriched waters affects the quality of surface and groundwater resources, limiting their uses for various purposes. Particularly, manganese pollution has attracted attention due to its impact on human health and its negative effects on ecosystems. Applications of nanomaterials such as graphene oxide (GO) have emerged as potential candidates for removing complex contaminants. In this study, we present the preliminary results of the removal of Mn(II) ions from acidic waters by using GO functionalized with zinc oxide nanoparticles (ZnO). Batch adsorption experiments were performed under two different acidity conditions (pH1 = 5.0 and pH2 = 4.0), in order to evaluate the impact of acid pH on the adsorption capacity. We observed that the adsorption of Mn(II) was independent of the pHPZC value of the nanoadsorbents. The qmax with GO/ZnO nanocomposites was 5.6 mg/g (34.1% removal) at pH = 5.0, while with more acidic conditions (pH = 4.0) it reached 12.6 mg/g (61.2% removal). In turn, the results show that GO/ZnO nanocomposites were more efficient to remove Mn(II) compared with non-functionalized GO under the pH2 condition (pH2 = 4.0). Both Langmuir and Freundlich models fit well with the adsorption process, suggesting that both mechanisms are involved in the removal of Mn(II) with GO and GO/ZnO nanocomposites. Furthermore, adsorption isotherms were efficiently modeled with the pseudo-second-order kinetic model. These results indicate that the removal of Mn(II) by GO/ZnO is strongly influenced by the pH of the solution, and the decoration with ZnO significantly increases the adsorption capacity of Mn(II) ions. These findings can provide valuable information for optimizing the design and configuration of wastewater treatment technologies based on GO nanomaterials for the removal of Mn(II) from natural and industrial waters.

14.
Rev Med Suisse ; 17(734): 732-736, 2021 Apr 14.
Artículo en Francés | MEDLINE | ID: mdl-33852208

RESUMEN

The emergence of cases of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections during recent years has given rise to country-specific surveillance and control strategies. The pandemic we are going through has at least helped to remind the importance of applying basic hygiene practices to prevent and control the spread of numerous other pathogens, including multidrug-resistant bacteria including CA-MRSA. However, once identified, patients who are healthy carriers of CA-MRSA may benefit from decolonization according to an established protocol.


L'émergence de cas d'infections communautaires à Staphylococcus aureus (S. aureus) résistant à la méticilline, au cours des dernières années, a donné naissance à des stratégies de surveillance et de contrôle propre à chaque pays. Les mesures préventives restent le meilleur moyen de lutter contre la propagation et l'expansion du réservoir communautaire de S. aureus multirésistant. La pandémie que nous traversons aujourd'hui aura peut-être au moins comme avantage d'avoir remis au goût du jour les pratiques d'hygiène de base, permettant d'éviter de nombreuses autres propagations de germes, dont les bactéries multirésistantes. Néanmoins, une fois identifiés, les patients porteurs sains de S. aureus multirésistant peuvent bénéficier d'une décolonisation selon un protocole établi.


Asunto(s)
Infecciones Comunitarias Adquiridas , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/prevención & control , Farmacorresistencia Bacteriana Múltiple , Humanos , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus
15.
Clin Infect Dis ; 70(9): 1891-1897, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-31613316

RESUMEN

BACKGROUND: Carriers of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) who receive cephalosporin-based prophylaxis have twice the risk of surgical site infection (SSI) following colorectal surgery as noncarriers. We tested whether ESBL-PE screening and personalized prophylaxis with ertapenem reduces SSI risk among carriers. METHODS: We conducted a prospective nonrandomized, nonblinded, interventional study in 3 hospitals in Israel, Switzerland, and Serbia. Patients were screened for ESBL-PE carriage before elective colorectal surgery. During the baseline phase, departmental guidelines advised prophylaxis with a cephalosporin plus metronidazole. In the intervention phase, guidelines were changed for ESBL-PE carriers to receive ertapenem. The primary outcome was any type of SSI within 30 days. We calculated adjusted risk differences (ARDs) following logistic regression. RESULTS: The intention-to-treat analysis compared 209 ESBL-PE carriers in the baseline phase to 269 in the intervention phase. SSI rates were 21.5% and 17.5%, respectively (ARD, -4.7% [95% confidence interval {CI}, -11.8% to 2.4%]). Unplanned crossover was high (15%), so to assess efficacy we performed an as-treated analysis comparing 247 patients who received cephalosporin-based prophylaxis with 221 who received ertapenem. SSI rates were 22.7% and 15.8%, respectively (ARD, -7.7% [95% CI, -14.6% to -.8%]), and rates of SSI caused by ESBL-PE were 6.5% and 0.9%, respectively (ARD, -5.6% [95% CI, -8.9% to -2.3%]). There was no significant difference in the rate of deep SSI. The number needed to treat to prevent 1 SSI in ESBL-PE carriers was 13. CONCLUSIONS: Screening for ESBL-PE carriage before colorectal surgery and personalizing prophylaxis for carriers is efficacious in reducing SSI.


Asunto(s)
Cirugía Colorrectal , Infecciones por Enterobacteriaceae , Antibacterianos/uso terapéutico , Cirugía Colorrectal/efectos adversos , Enterobacteriaceae , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/prevención & control , Ertapenem , Humanos , Israel , Estudios Prospectivos , Suiza , beta-Lactamasas
16.
Microb Pathog ; 149: 104349, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32562812

RESUMEN

Scedosporium apiospermum is an opportunistic emerging pathogen that can develop in both immunosuppressive and immunocompetent patients with pulmonary infections. Neutrophils are recognized as critical cells in the early response to a fungal infection through different mechanisms that eliminate or control the infection such as neutrophil extracellular traps (NETs). In this work, we investigate the presence of NETs in the lung tissue of immunocompetent mice infected with Scedosporium apiospermum. In the histopathological study the presence of filamentous basophilic material with hematoxylin-eosin and periodic acid Schiff stains suggestive of extracellular DNA was observed. We demonstrated the presence of NETs by immunofluorescence staining of extracellular DNA, myeloperoxidase, and elastase in lung tissue. Our results showed that on days 1 and 3 post-infection extracellular DNA, myeloperoxidase, and elastase correlate with areas of high concentration of cell infiltrates and fungal structures. The observation of fungal structures in the tissue decreased as did the presence of NETs by day 5 post-infection. We suggest that NETs release may play an important role in the early containment of Scedosporium apiospermum lung infection.


Asunto(s)
Trampas Extracelulares , Micosis , Scedosporium , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Neutrófilos
17.
Microb Pathog ; 142: 104073, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-32070747

RESUMEN

A pulmonary infection model due to Scedosporium apiospermum in immunocompetent mice was developed. BALB/c mice were infected by endotracheal intubation with 5 × 106 conidia/mouse and disease progression was evaluated on days 1, 3, 5, 7, 11, 16, 21, 30, 50 and 60 post-infection through quantitative culture and histopathological analysis of lungs, livers, spleens, brains, and kidneys. There was no extrapulmonary dissemination during the study nor shown to be a lethal infection. The fungal burden in lungs was maintained from day 1-5 and gradually decreased by day 30 post-challenge. On day 60, 30% of mice showed complete elimination of the fungus. Severe alterations in the lung tissue were observed, as well as the presence of conidia and hyphae surrounded by a cellular infiltrate composed mainly of neutrophils in the first days of the infection. The elimination of fungal cells and normal tissue morphology were recovered throughout the study.

18.
Cerebellum ; 19(4): 527-535, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32285347

RESUMEN

Spinocerebellar ataxia subtypes 1, 3, and 6 (SCA1, MJD/SCA3, and SCA6) are among the most prevalent autosomal dominant cerebellar ataxias worldwide, but their relative frequencies in Peru are low. Frequency of large normal (LN) alleles at spinocerebellar ataxia-causative genes has been proposed to be associated with disease prevalence. To investigate the allelic distribution of the CAG repeat in ATXN1, ATXN3, and CACNA1A genes in a Peruvian mestizo population and examine their association with the relative frequency of SCA1, MJD/SCA3, and SCA6 across populations. We genotyped 213 healthy mestizo individuals from Northern Lima, Peru, for ATXN1, ATXN3, and CACNA1A using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE). We compared the frequency of LN alleles and relative disease frequency between populations. We also tested 40 samples for CAT repeat interruptions within the CAG tract of ATXN1. We found no association between disease frequency and population frequency of LN alleles at ATXN1 and ATXN3. All 40 ATXN1 samples tested for CAT interruptions were positive. Frequency of LN alleles at CACNA1A correlates with SCA6 frequency across several populations, but this effect was largely driven by data from a single population. Low frequency of SCA1 and MJD/SCA3 in Peru is not explained by frequency of LN alleles at ATXN1 and ATXN3, respectively. The observed correlation between CACNA1A LN alleles and SCA6 frequency requires further assessment.


Asunto(s)
Ataxina-1/genética , Ataxina-3/genética , Canales de Calcio/genética , Ataxia Cerebelosa/genética , Proteínas Represoras/genética , Adulto , Alelos , Femenino , Genotipo , Humanos , Enfermedad de Machado-Joseph/genética , Masculino , Persona de Mediana Edad , Perú , Ataxias Espinocerebelosas/genética , Expansión de Repetición de Trinucleótido
19.
Molecules ; 25(14)2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-32650371

RESUMEN

In recent years, carbon nanotubes (CNTs) have been intensively studied as an effective adsorbent for the removal of pollutants from wastewater. One of the main problems for its use corresponds to the agglomeration of the CNTs due to the interactions between them, which prevents using their entire surface area. In this study, we test the effect of dispersion of oxidized multi-walled carbon nanotubes (MWCNTs) on the removal of heavy metals from acidic solutions. For this, polyurethane filters were dyed with a well-dispersed oxidized MWCNTs solution using chemical and mechanical dispersion methods. Filters were used in column experiments, and the sorption capacity increased more than six times (600%) compared to experiments with suspended MWCNTs. Further, kinetic experiments showed a faster saturation on MWCNTs in column experiments. These results contribute to a better understanding of the effect of dispersion on the use of CNTs as heavy metal ions adsorbent.


Asunto(s)
Metales Pesados/química , Nanotubos de Carbono/química , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Adsorción
20.
Clin Infect Dis ; 68(10): 1699-1704, 2019 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-30204851

RESUMEN

BACKGROUND: Antibiotic prophylaxis that covers enteric pathogens is essential in preventing surgical site infections (SSIs) after colorectal surgery. Current prophylaxis regimens do not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). We aimed to determine whether the risk of SSI following colorectal surgery is higher in ESBL-PE carriers than in noncarriers. METHODS: We conducted a prospective cohort study of patients who underwent elective colorectal surgery in 3 hospitals in Israel, Switzerland, and Serbia between 2012 and 2017. We included patients who were aged ≥18 years, were screened for ESBL-PE carriage before surgery, received routine prophylaxis with a cephalosporin plus metronidazole, and did not have an infection at the time of surgery. The exposed group was composed of ESBL-PE-positive patients. The unexposed group was a random sample of ESBL-PE-negative patients. We collected data on patient and surgery characteristics and SSI outcomes. We fit logistic mixed effects models with study site as a random effect. RESULTS: A total of 3600 patients were screened for ESBL-PE; 13.8% were carriers SSIs occurred in 55/220 carriers (24.8%) and 49/440 noncarriers (11.1%, P < .001). In multivariable analysis, ESBL-PE carriage more than doubled the risk of SSI (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.50-3.71). Carriers had higher risk of deep SSI (OR, 2.25; 95% CI, 1.27-3.99). SSI caused by ESBL-PE occurred in 7.2% of carriers and 1.6% of noncarriers (OR, 4.23; 95% CI, 1.70-10.56). CONCLUSIONS: ESBL-PE carriers who receive cephalosporin-based prophylaxis are at increased risk of SSI following colorectal surgery.


Asunto(s)
Profilaxis Antibiótica , Portador Sano/microbiología , Cirugía Colorrectal/efectos adversos , Infecciones por Enterobacteriaceae/etiología , Infección de la Herida Quirúrgica/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Portador Sano/prevención & control , Cefalosporinas/administración & dosificación , Cefalosporinas/efectos adversos , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/enzimología , Infecciones por Enterobacteriaceae/prevención & control , Heces/microbiología , Femenino , Humanos , Israel , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Serbia , Infección de la Herida Quirúrgica/prevención & control , Suiza , beta-Lactamasas
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