RESUMO
Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In a previous study, we found that post-extinction L-DOPA administration improved extinction memory retrieval 24 h later. Furthermore, spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predicted extinction memory retrieval, L-DOPA increased the number of these reactivations, and this mediated the effect of L-DOPA on extinction memory retrieval. Here, we conducted a preregistered replication study of this work in healthy male participants. We confirm that spontaneous post-extinction vmPFC reactivations predict extinction memory retrieval. This predictive effect, however, was only observed 90 min after extinction, and was not statistically significant at 45 min as in the discovery study. In contrast to our previous study, we find no evidence that L-DOPA administration significantly enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity. Further, trait salivary alpha-amylase negatively predicts retrieval, and this effect is reduced by L-DOPA treatment. Importantly, the latter findings result from non-preregistered analyses and thus further investigation is needed.
Assuntos
Dopamina , alfa-Amilases Salivares , Humanos , Masculino , Dopamina/farmacologia , Levodopa/farmacologia , alfa-Amilases Salivares/farmacologia , Extinção Psicológica/fisiologia , Memória , Córtex Pré-Frontal/fisiologiaRESUMO
BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54â71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3â7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10â18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100â190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7â28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5â0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).
Assuntos
COVID-19 , Pneumonia , Síndrome do Desconforto Respiratório , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/terapia , Estado Terminal/terapia , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Intubação Intratraqueal , Oxigênio , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: In recent years, cases have been reported in which unexpected systemic hypersensitivity reactions occurred in patients dialyzed with polysulfone- or polyethersulfone-biocompatible membranes in the absence of other risk factors. The pathomechanisms involved in these reactions are largely unknown. OBJECTIVE: To characterize hypersensitivity reactions to polysulfone hemodialysis using clinical and laboratory data and to identify biomarkers suitable for endotype identification and diagnosis. METHODS: We prospectively collected data from 29 patients with suspected hypersensitivity reactions to polysulfone hemodialysis membranes. Clinical laboratory parameters such as tryptase, blood cell counts, and complement levels were recorded. Acute samples were obtained from 18 cases for the ex vivo assessment of basophil activation by flow cytometry analysis of CD63, CD203, and FcεRI cell membrane expression. Serum cytokines and anaphylatoxin concentrations were evaluated in 16 cases by Luminex and cytometric bead array analysis. RESULTS: Tryptase was elevated during the acute reaction in 4 cases. Evidence of basophil activation was obtained in 10 patients. Complement activation was found in only 2 cases. However, C5a serum levels tended to increase during the acute reaction in those patients with hypoxemia. Significantly higher serum levels of interleukin-6 were observed during the acute reactions to polysulfone hemodialysis (P = .0103). CONCLUSION: Based on biomarker analysis, various endotypes were identified, including type I-like (with the involvement of mast cells or basophils), complement, and cytokine (interleukin-6) release-related reactions, with some patients showing mixed reactions. Further research is needed to unravel the exact mechanisms involved in the activation of these cellular and molecular pathways.
Assuntos
Hipersensibilidade , Membranas Artificiais , Basófilos , Humanos , Hipersensibilidade/etiologia , Interleucina-6 , Polímeros , Diálise Renal/efeitos adversos , Sulfonas , Triptases/metabolismoRESUMO
Adult humans make effortless use of multisensory signals and typically integrate them in an optimal fashion.1 This remarkable ability takes many years for normally sighted children to develop.2,3 Would individuals born blind or with extremely low vision still be able to develop multisensory integration later in life when surgically treated for sight restoration? Late acquisition of such capability would be a vivid example of the brain's ability to retain high levels of plasticity. We studied the development of multisensory integration in individuals suffering from congenital dense bilateral cataract, surgically treated years after birth. We assessed cataract-treated individuals' reliance on their restored visual abilities when estimating the size of an object simultaneously explored by touch. Within weeks to months after surgery, when combining information from vision and touch, they developed a multisensory weighting behavior similar to matched typically sighted controls. Next, we tested whether cataract-treated individuals benefited from integrating vision with touch by increasing the precision of size estimates, as it occurs when integrating signals in a statistically optimal fashion.1 For participants retested multiple times, such a benefit developed within months after surgery to levels of precision indistinguishable from optimal behavior. To summarize, the development of multisensory integration does not merely depend on age, but requires extensive multisensory experience with the world, rendered possible by the improved post-surgical visual acuity. We conclude that early exposure to multisensory signals is not essential for the development of multisensory integration, which can still be acquired even after many years of visual deprivation.
Assuntos
Catarata , Percepção do Tato , Adulto , Catarata/congênito , Criança , Humanos , Tato , Visão Ocular , Percepção VisualRESUMO
Genetic defects in the three SH3 and multiple ankyrin repeat domains (SHANK) genes (SHANK1, SHANK2, and SHANK3) are associated with multiple major neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BPD). Psychostimulant-induced hyperactivity is a commonly applied paradigm to assess behavioral phenotypes related to BPD and considered to be the gold standard for modeling mania-like elevated drive in mouse models. Therefore, the goal of our present study was to test whether Shank1 plays a role in the behavioral effects of psychostimulants and whether this is associated with genotype-dependent neurochemical alterations. To this aim, male and female null mutant Shank1-/- mice were treated with d-amphetamine (AMPH; 2.5 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, commonly known as ecstasy; 20 mg/kg), and psychostimulant-induced hyperactivity was compared to heterozygous Shank1+/- and wildtype Shank1+/+ littermate controls. Results show that Shank1-/- mice display reduced psychostimulant-induced hyperactivity, although psychostimulants robustly stimulated locomotor activity in littermate controls. Shank1 deletion effects emerged throughout development, were particularly prominent in adulthood, and seen in response to both psychostimulants, i.e., AMPH and MDMA. Specifically, while AMPH-induced hyperactivity was reduced but still detectable in Shank1-/- mice, MDMA-induced hyperactivity was robustly blocked and completely absent in Shank1-/- mice. Reduced efficacy of psychostimulants to stimulate hyperactivity in Shank1-/- mice might be associated with alterations in the neurochemical architecture in prefrontal cortex, nucleus accumbens, and hypothalamus. Our observation that psychostimulant-induced hyperactivity is reduced rather than enhanced in Shank1-/- mice clearly speaks against a behavioral phenotype with relevance to BPD. Lack of BPD-like phenotype is consistent with currently available human data linking mutations in SHANK2 and SHANK3 but not SHANK1 to BPD.
RESUMO
The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm3) than the rest (CB: 23 ppb, 184 cells/mm3, emphysema: 27 ppb, 159 cells/mm3; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.
Assuntos
Asma/imunologia , Eosinofilia/imunologia , Óxido Nítrico/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Idoso , Idoso de 80 Anos ou mais , Asma/complicações , Asma/metabolismo , Asma/fisiopatologia , Testes Respiratórios , Bronquite Crônica/complicações , Bronquite Crônica/imunologia , Bronquite Crônica/metabolismo , Bronquite Crônica/fisiopatologia , Proteína C-Reativa/imunologia , Progressão da Doença , Proteína Catiônica de Eosinófilo/imunologia , Eosinofilia/complicações , Eosinofilia/metabolismo , Eosinófilos , Feminino , Hospitalização , Humanos , Imunoglobulina E/imunologia , Contagem de Leucócitos , Masculino , Óxido Nítrico/análise , Pró-Calcitonina/imunologia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/imunologia , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/fisiopatologiaRESUMO
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Assuntos
Lipoma/complicações , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/etiologia , Neoplasias Gástricas/complicações , Ultrassonografia/métodos , Abscesso/complicações , Idoso , Drenagem , Feminino , Humanos , Lipoma/microbiologia , Abscesso Hepático/terapia , Tomografia Computadorizada por Raios X/métodosRESUMO
We can estimate the veridical size of nearby objects reasonably well irrespective of their viewing distance. This perceptual capability, termed size constancy, is accomplished by combining information about retinal image size together with the viewing distance, or using the relational information available in the scene, via direct perception [1]. A previous study [2] showed that children typically underestimate the size of a distant object. This underestimation is reduced with time, suggesting that years of visual experience may be essential for attaining true size constancy. But what if you have had very limited vision during the early years of life? We studied 23 Ethiopian children suffering from bilateral, early-onset cataract, who were surgically treated only years after birth. Surprisingly, most children were able to estimate object size reasonably well irrespective of distance; in fact, they usually tended to overestimate the far-object size. Closer examination indicated that, although before surgery the patients were diagnosed as having a full, mature bilateral cataract, they nevertheless had some residual form of vision, typically limited to very close range. Gandhi et al.[3] earlier reported immediate susceptibility to geometric visual illusions in a similar group of newly-sighted children, concluding that size constancy was probably innate. We suggest that their immediate ability to judge physical size irrespective of distance is more likely to result from their previous visual experience.
Assuntos
Extração de Catarata , Percepção de Distância , Percepção de Tamanho , Adolescente , Criança , Pré-Escolar , Etiópia , Feminino , Humanos , MasculinoRESUMO
Laparoscopic surgery for abdominal wall hernias improves short-term results as compared with open hernia surgery. However, no evidence exists to recommend this approach for pseudohernias, which are abdominal wall defects postsurgery caused by denervation and muscular atrophy. The purpose of this study is to analyze whether the laparoscopic approach benefits patients with a pseudohernia. A prospective nonrandomized, single-center clinical study was conducted of 24 patients operated on for pseudohernia. This study was designed with the basic principle of one unit, one surgeon, one mesh, and two techniques (laparoscopic or open double prosthetic repair). The primary end point was assessment of the abdominal wall according to: 1) abdominal perimeter; 2) computed tomography scan; and 3) degree of satisfaction. The secondary end points were intraoperative parameters and comorbidity. Laparoscopy offered no benefits in patients with pseudohernias. Open surgery offered no significant differences in intra- and postoperative morbidity, but if the initial weakness improved with a decrease in abdominal perimeter and visceral content, then there was more than 90 per cent satisfaction (P < 0.05). The laparoscopic approach does not improve the bulge caused by abdominal muscle atrophy. The option of a muscular and prosthetic reconstruction provides better clinical and cosmetic results.
Assuntos
Parede Abdominal/cirurgia , Tomada de Decisões , Hérnia Ventral/complicações , Herniorrafia/métodos , Laparoscopia/métodos , Atrofia Muscular/complicações , Telas Cirúrgicas , Contraindicações , Feminino , Seguimentos , Hérnia Ventral/diagnóstico , Hérnia Ventral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/diagnóstico , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , CicatrizaçãoRESUMO
BACKGROUND AND OBJECTIVE: The complete preoperative evaluation of the colon is necessary in colorectal cancer owing to the frequency of synchronous tumors. The objective of this paper was to evaluate the utility of the computed tomography colonography (CTC) as opposed to barium enema (BEDC) when the colonoscopy was incomplete or impossible to perform. PATIENTS AND METHOD: Group A: 50 patients with colorectal cancer with subsequent incomplete colonoscopy and BEDC. Group B: 40 patients with colorectal cancer with subsequent incomplete colonoscopy and CTC. As gold standard to match the tests, we carried out the pathological study of the surgical piece and the colonoscopy 3 months after surgery. In addition, we studied the degree of satisfaction, indirect effect and cost by test. RESULTS: There were no synchronous tumors. For the detection of colonic polyps, we obtained for the CTC the following values: Sensitivity = 85.7%, Specificity = 96.1%, PPV = 92.3%, NPV = 92.6%, CPP = 21,97 and CPN =0,15. And for BEDC, the values were: Sensitivity = 23.5%, Specificity = 92.8%, PPV = 80%, NPV = 71.7%, CPP = 3.26 and CPN = 0.82 (p < 0.001). The degree of satisfaction was greater with CTC than with BEDC (p < 0.05). There were no differences as far as indirect effect was concerned. The cost of CTC was 33.18 Euros and it was 42.42 Euros for BEDC. CONCLUSION: CTC is better than BEDC both to confirm the presence of polyps in colon and to rule out the absence of them in patients in whom a complete the study of the colon by colonoscopy has not been possible.
Assuntos
Sulfato de Bário , Colonografia Tomográfica Computadorizada , Colonoscopia , Neoplasias Colorretais/diagnóstico , Enema , Idoso , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-OperatóriosRESUMO
BACKGROUND: Nosocomial transmission of hepatitis C virus (HCV) in hemodialysis (HD) units is well established. In units with a high prevalence of HCV infection, the implementation of universal precautionary measures may not suffice in order to decrease the incidence and prevalence of HCV. In this setting strict isolation practices can be useful in order to achieve this goal. METHODS: The incidence and prevalence of HCV infection amongst all HD and peritoneal dialysis (PD) patients from the province of Albacete, Spain, have been studied from 1992 to 2003.Through the 1993-1995 period chronic HD patients were treated either in a room exclusively for HCV- patients or in a room shared by HCV+ and HCV- patients. Complete separation of HCV+ and HCV- patients was implemented in 1995. Acute patients have been separated since 1992. The implementation of universal precautions was applied throughout the period. RESULTS: There has not been a single seroconversion in the rooms where only HCV- patients were dialyzed during the 11 years of follow-up. There were two seroconversions in the rooms shared for 3 years by both HCV+ and HCV- patients. In 1995 the prevalence of HCV+ cases in HD and PD was 21.6 and 23.2%, respectively. Since then it has decreased steadily and in parallel for both therapies, and the current prevalence is 6.8% in HD and 5.7% in PD. CONCLUSIONS: In HD units with a high prevalence of HCV+ patients, strict isolation in combination with implementation of universal prevention measures can eliminate nosocomial transmission and obtain a long-term reduction in prevalence.
Assuntos
Infecção Hospitalar/epidemiologia , Hepatite C/epidemiologia , Isolamento de Pacientes/estatística & dados numéricos , Diálise Peritoneal/efeitos adversos , Diálise Renal/efeitos adversos , Doença Aguda , Infecção Hospitalar/etiologia , Infecção Hospitalar/prevenção & controle , Unidades Hospitalares de Hemodiálise , Hepatite C/etiologia , Hepatite C/prevenção & controle , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Transplante de Rim/estatística & dados numéricos , Prevalência , Precauções UniversaisRESUMO
Development of tuberculosis infection in a renal transplant patient is infrequent in Spain, although the prevalence is higher than in the general population. These patients usually receive calcineurin inhibitors as the main component of their immunosuppressive treatment. The metabolism of these drugs, whether cyclosporine or tacrolimus, involves cytochrome P-450 3A. Rifampin, a widely used agent in the treatment of tuberculosis, is also an important inducer of cytochrome P-450 3A metabolism and has the capacity to decrease serum levels of the calcineurin inhibitors. This metabolic interaction makes pharmacologic management of tuberculosis-infected transplant patients more complex and can result in a higher risk of acute rejection caused by decreased levels of the immunosuppressant in the blood. The authors present a case of a renal transplant patient with a soft tissue infection caused by Mycobacterium tuberculosis who was treated with rifabutin instead of rifampin, with excellent results in terms of graft survival and overall survival. The use of rifabutin allowed the authors to achieve better control of circulating immunosuppressant levels and a lower probability of acute graft rejection.