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1.
Trends Hear ; 26: 23312165221117081, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35929144

RESUMO

Non-traumatic noise exposure has been shown in animal models to impact the processing of envelope cues. However, evidence in human studies has been conflicting, possibly because the measures have not been specifically parameterized based on listeners' exposure profiles. The current study examined young dental-school students, whose exposure to high-frequency non-traumatic dental-drill noise during their course of study is systematic and precisely quantifiable. Twenty-five dental students and twenty-seven non-dental participants were recruited. The listeners were asked to recognize unvoiced sentences that were processed to contain only envelope cues useful for recognition and have been filtered to frequency regions inside or outside the dental noise spectrum. The sentences were presented either in quiet or in one of the noise maskers, including a steady-state noise, a 16-Hz or 32-Hz temporally modulated noise, or a spectrally modulated noise. The dental students showed no difference from the control group in demographic information, audiological screening outcomes, extended high-frequency thresholds, or unvoiced speech in quiet, but consistently performed more poorly for unvoiced speech recognition in modulated noise. The group difference in noise depended on the filtering conditions. The dental group's degraded performances were observed in temporally modulated noise for high-pass filtered condition only and in spectrally modulated noise for low-pass filtered condition only. The current findings provide the most direct evidence to date of a link between non-traumatic noise exposure and supra-threshold envelope processing issues in human listeners despite the normal audiological profiles.

2.
Bioinformatics ; 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35695743

RESUMO

SUMMARY: Here we introduce SNIKT, a command-line tool for sequence-independent visual confirmation and input-assisted removal of adapter contamination in whole-genome shotgun or metagenomic shotgun long-read sequencing DNA or RNA data. AVAILABILITY AND IMPLEMENTATION: SNIKT is implemented in R and is compatible with Unix-like platforms. The source code, along with documentation, is freely available under an MIT license at https://github.com/piyuranjan/SNIKT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

3.
Front Allergy ; 3: 851993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769569

RESUMO

There is heterogeneity inherent in the immune responses of individual mice in murine models of food allergy, including anaphylaxis, similar to the clinical heterogeneity observed in humans with food allergies to a defined food. One major driver of this heterogeneity may be differences in the microbiome between sensitized individuals. Our laboratory and others have reported that disruption of the microbiome (dysbiosis) by broad spectrum antibiotics and/or yeast colonization can alter systemic immunity and favor the development of mucosal Type 2 immunity to aeroallergens. Our objective was to use a well-characterized murine model (Balb/c mice) of food allergies (chicken egg ovalbumin, OVA) and determine if antibiotic-mediated dysbiosis (including C. albicans colonization) could enhance the manifestation of food allergies. Furthermore, we sought to identify elements of the microbiome and host response that were associated with this heterogeneity in the anaphylactic reaction between individual food allergen-sensitized mice. In our dataset, the intensity of the anaphylactic reactions was most strongly associated with a disrupted microbiome that included colonization by C. albicans, loss of a specific Lachnoclostridium species (tentatively, Lachnoclostridium YL32), development of a highly polarized Type 2 response in the intestinal mucosa and underlying tissue, and activation of mucosal mast cells. Serum levels of allergen-specific IgE were not predictive of the response and a complete absence of a microbiome did not fully recapitulate the response. Conventionalization of germ-free mice resulted in Akkermansia muciniphila outgrowth and a higher degree of heterogeneity in the allergic response. C57BL/6 mice remained resistant even under the same dysbiosis-inducing antibiotic regimens, while changes in the microbiome markedly altered the reactivity of Balb/c mice to OVA, as noted above. Strikingly, we also observed that genetically identical mice from different rooms in our vivarium develop different levels of a Type 2 response, as well as anaphylactic reactions. The intestinal microbiome in these mice also differed between rooms. Thus, our data recapitulate the heterogeneity in anaphylactic reactions, ranging from severe to none, seen in patients that have circulating levels of food allergen-reactive IgE and support the concept that alterations in the microbiome can be one factor underlying this heterogeneity.

4.
J Acoust Soc Am ; 151(5): 3219, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35649920

RESUMO

Salient interruptions draw attention involuntarily. Here, we explored whether this effect depends on the spatial and temporal relationships between a target stream and interrupter. In a series of online experiments, listeners focused spatial attention on a target stream of spoken syllables in the presence of an otherwise identical distractor stream from the opposite hemifield. On some random trials, an interrupter (a cat "MEOW") occurred. Experiment 1 established that the interrupter, which occurred randomly in 25% of the trials in the hemifield opposite the target, degraded target recall. Moreover, a majority of participants exhibited this degradation for the first target syllable, which finished before the interrupter began. Experiment 2 showed that the effect of an interrupter was similar whether it occurred in the opposite or the same hemifield as the target. Experiment 3 found that the interrupter degraded performance slightly if it occurred before the target stream began but had no effect if it began after the target stream ended. Experiment 4 showed decreased interruption effects when the interruption frequency increased (50% of the trials). These results demonstrate that a salient interrupter disrupts recall of a target stream, regardless of its direction, especially if it occurs during a target stream.


Assuntos
Rememoração Mental , Humanos
5.
Brain Sci ; 12(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35326306

RESUMO

Striatal dopamine dysfunction is associated with the altered top-down modulation of pain processing. The dopamine D2-like receptor family is a potential substrate for such effects due to its primary expression in the striatum, but evidence for this is currently lacking. Here, we investigated the effect of pharmacologically manipulating striatal dopamine D2 receptor activity on the anticipation and perception of acute pain stimuli in humans. Participants received visual cues that induced either certain or uncertain anticipation of two pain intensity levels delivered via a CO2 laser. Rating of the pain intensity and unpleasantness was recorded. Brain activity was recorded with EEG and analysed via source localisation to investigate neural activity during the anticipation and receipt of pain. Participants completed the experiment under three conditions, control (Sodium Chloride), D2 receptor agonist (Cabergoline), and D2 receptor antagonist (Amisulpride), in a repeated-measures, triple-crossover, double-blind study. The antagonist reduced an individuals' ability to distinguish between low and high pain following uncertain anticipation. The EEG source localisation showed that the agonist and antagonist reduced neural activations in specific brain regions associated with the sensory integration of salient stimuli during the anticipation and receipt of pain. During anticipation, the agonist reduced activity in the right mid-temporal region and the right angular gyrus, whilst the antagonist reduced activity within the right postcentral, right mid-temporal, and right inferior parietal regions. In comparison to control, the antagonist reduced activity within the insula during the receipt of pain, a key structure involved in the integration of the sensory and affective aspects of pain. Pain sensitivity and unpleasantness were not changed by D2R modulation. Our results support the notion that D2 receptor neurotransmission has a role in the top-down modulation of pain.

6.
Materials (Basel) ; 15(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35329501

RESUMO

The surface roughness of additively manufactured (AM) components can have deleterious effects on the properties of the final part, such as corrosion resistance and fatigue life. Modification of the surface finish or parts produced by AM processes, such as cold spray, through methods such as mass finishing, can help to mitigate some of these issues. In this work, the surface evolution of as-produced copper cold sprayed material consolidations was studied through mass finishing. Three different copper powders attained by different production methods and of different sizes were used as feedstock. The surface topography of the cold spray deposits was measured as a function of the mass finishing time for the three copper cold spray samples and analyzed in terms of relative area and complexity, revealing an inverse correlation relating material removal rate and hardness/strength of the cold sprayed deposits. The material removal rate was also affected by the quality of the cold spray deposition, as defined by deposition efficiency (DE). Large initial drops in relative area and complexity are also likely due to the removal of loosely bonded powders at the start of mass finishing. Based on this study, the cold spray parameters that affect the rate of mass finishing have been explored.

7.
PLoS One ; 17(3): e0265023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35298489

RESUMO

BACKGROUND: The microbiome is an important and increasingly-studied mediator of organismal metabolism, although how the microbiome affects metabolism remains incompletely understood. Many investigators use antibiotics to experimentally perturb the microbiome. However, antibiotics have poorly understood yet profound off-target effects on behavior and diet, including food and water aversion, that can confound experiments and limit their applicability. We thus sought to determine the relative influence of microbiome modulation and off-target antibiotic effects on the behavior and metabolic activity of mice. RESULTS: Mice treated with oral antibiotics via drinking water exhibited significant weight loss in fat, liver, and muscle tissue. These mice also exhibited a reduction in water and food consumption, with marked variability across antibiotic regimens. While administration of bitter-tasting but antimicrobially-inert compounds caused a similar reduction in water consumption, this did not cause tissue weight loss or reduced food consumption. Mice administered intraperitoneal antibiotics (bypassing the gastrointestinal tract) exhibited reduced tissue weights and oral intake, comparable to the effects of oral antibiotics. Antibiotic-treated germ-free mice did not have reduced tissue weights, providing further evidence that direct microbiome modulation (rather than behavioral effects) mediates these metabolic changes. CONCLUSIONS: While oral antibiotics cause profound effects on food and water consumption, antibiotic effects on organismal metabolism are primarily mediated by microbiome modulation. We demonstrate that tissue-specific weight loss following antibiotic administration is due primarily to microbiome effects rather than food and water aversion, and identify antibiotic regimens that effectively modulate gut microbiota while minimizing off-target behavioral effects.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Antibacterianos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Água/farmacologia , Redução de Peso
8.
Nat Commun ; 13(1): 751, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136068

RESUMO

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , SARS-CoV-2/genética , Universidades , COVID-19/prevenção & controle , COVID-19/virologia , Busca de Comunicante , Genoma Viral/genética , Genômica , Humanos , Filogenia , RNA Viral/genética , Fatores de Risco , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Estudantes , Reino Unido/epidemiologia , Universidades/estatística & dados numéricos
9.
Sci Rep ; 12(1): 3114, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35210470

RESUMO

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories.


Assuntos
SARS-CoV-2
10.
Ann Am Thorac Soc ; 19(8): 1338-1345, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35157559

RESUMO

Rationale: Supplemental oxygen is among the most commonly administered therapies in intensive care units (ICUs). High supplemental oxygen exposure has been associated with harm in observational human studies and animal models, yet no consensus exists regarding which dose and duration of high oxygen constitutes harmful hyperoxemia, and little is known regarding the clinical factors that predict potentially injurious exposure. Objectives: To determine the dose and duration of the arterial partial pressure of oxygen (PaO2) associated with mortality among mechanically ventilated patients and to identify the clinical factors that predict this exposure. Methods: We performed a retrospective cohort study of patients who received invasive mechanical ventilation at a single academic institution in 2017 and 2018. We used a generalized additive model to visualize the relationship between the measured PaO2 via arterial blood gas measurements and 30-day mortality. We used multivariable logistic regression to identify patient- and hospital-level factors that predict exposure to harmful hyperoxemia. Results: We analyzed 2,133 patients with 33,310 arterial blood gas measurements obtained during mechanical ventilation. We identified a U-shaped relationship between PaO2 and mortality, in which PaO2 was positively correlated with mortality above a threshold of 200 mm Hg. A total of 1,184 patients (55.5%) had at least one PaO2 measurement above this threshold. If patients spent an entire day exposed to PaO2 > 200 mm Hg, they had 2.19 (95% confidence interval [CI], 1.33-3.60; P = 0.002) greater odds of 30-day mortality in an adjusted analysis. Any exposure to severe hyperoxemia (PaO2 > 200 mm Hg) was associated with mortality (odds ratio, 1.29; 95% CI, 1.04-1.59; P = 0.021). The strongest clinical predictor of severe hyperoxemia exposure was the identity of the ICU in which mechanical ventilation was delivered. Conclusions: Exposure to high arterial oxygen concentrations is common among mechanically ventilated patients, and the dose and duration of PaO2 ⩾ 200 mm Hg is associated with mortality. Severe hyperoxemia is highly variable across ICUs and is far more common in clinical practice than in recent randomized trials of oxygen-targeting strategies. Efforts to minimize this common and injurious exposure are needed.


Assuntos
Transtornos Respiratórios , Respiração Artificial , Gasometria , Estudos de Coortes , Humanos , Unidades de Terapia Intensiva , Oxigênio , Transtornos Respiratórios/etiologia , Respiração Artificial/efeitos adversos , Estudos Retrospectivos
11.
Microbiome ; 10(1): 2, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991717

RESUMO

BACKGROUND: In ecology, population density is a key feature of community analysis. Yet in studies of the gut microbiome, bacterial density is rarely reported. Studies of hospitalized patients commonly use rectal swabs for microbiome analysis, yet variation in their bacterial density-and the clinical and methodologic significance of this variation-remains undetermined. We used an ultra-sensitive quantification approach-droplet digital PCR (ddPCR)-to quantify bacterial density in rectal swabs from 118 hospitalized patients. We compared bacterial density with bacterial community composition (via 16S rRNA amplicon sequencing) and clinical data to determine if variation in bacterial density has methodological, clinical, and prognostic significance. RESULTS: Bacterial density in rectal swab specimens was highly variable, spanning five orders of magnitude (1.2 × 104-3.2 × 109 16S rRNA gene copies/sample). Low bacterial density was strongly correlated with the detection of sequencing contamination (Spearman ρ = - 0.95, p < 10-16). Low-density rectal swab communities were dominated by peri-rectal skin bacteria and sequencing contaminants (p < 0.01), suggesting that some variation in bacterial density is explained by sampling variation. Yet bacterial density was also associated with important clinical exposures, conditions, and outcomes. Bacterial density was lower among patients who had received piperacillin-tazobactam (p = 0.017) and increased among patients with multiple medical comorbidities (Charlson score, p = 0.0040) and advanced age (p = 0.043). Bacterial density at the time of hospital admission was independently associated with subsequent extraintestinal infection (p = 0.0028), even when controlled for severity of illness and comorbidities. CONCLUSIONS: The bacterial density of rectal swabs is highly variable, and this variability is of methodological, clinical, and prognostic significance. Microbiome studies using rectal swabs are vulnerable to sequencing contamination and should include appropriate negative sequencing controls. Among hospitalized patients, gut bacterial density is associated with clinical exposures (antibiotics, comorbidities) and independently predicts infection risk. Bacterial density is an important and under-studied feature of gut microbiome community analysis. Video abstract.


Assuntos
Microbioma Gastrointestinal , Microbiota , Bactérias/genética , Humanos , Microbiota/genética , RNA Ribossômico 16S/genética , Reto/microbiologia
12.
Eur J Neurosci ; 54(4): 5601-5619, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34250660

RESUMO

Body perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of complex regional pain syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between "passive" (i.e., no task demands and equiprobable digit stimulation) and "active" tactile processing (i.e., where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28-56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier's training, there is an unexpected increased decodability in the CRPS group compared with healthy volunteers (280-320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision-making and attentional control mechanisms in chronic CRPS.


Assuntos
Síndromes da Dor Regional Complexa , Ilusões , Percepção do Tato , Humanos , Tato
14.
Soc Cogn Affect Neurosci ; 16(12): 1234-1243, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34100542

RESUMO

Oxytocin promotes social affiliation across various species, in part by altering social cognition to facilitate approach behaviour. However, the effects of intranasal oxytocin on human social cognition are mixed, perhaps because its effects are context dependent and subject to inter-individual differences. Few studies have included explicit manipulations of social context to test this supposition. We examined oxytocin's effects on autobiographical memory recall in two contexts, with and without social contact, and evaluated whether these effects were moderated by depressive symptoms. Two non-clinical samples (Study 1, n = 48; Study 2, n = 63) completed randomised, placebo-controlled, within-subject experiments. We assessed autobiographical memory recall across two sessions (intranasal oxytocin or placebo) and two contexts (memories elicited by an experimenter or by computer). Overall, intranasal oxytocin increased ratings of the vividness of recalled memories during the social context only. Individuals with elevated depressive symptoms also recalled memories that were more negative following oxytocin relative to placebo only in the non-social context across the two studies. Findings highlight the negative consequences of increasing oxytocin bioavailability in vulnerable persons in the absence of social contact. Contextual factors such as social isolation among depressed populations may complicate the clinical use of oxytocin.


Assuntos
Memória Episódica , Ocitocina , Administração Intranasal , Depressão/tratamento farmacológico , Método Duplo-Cego , Humanos , Ocitocina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento Social , Meio Social
15.
Microbiome ; 9(1): 99, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952355

RESUMO

BACKGROUND: Low-biomass microbiome studies (such as those of the lungs, placenta, and skin) are vulnerable to contamination and sequencing stochasticity, which obscure legitimate microbial signal. While human lung microbiome studies have rigorously identified sampling strategies that reliably capture microbial signal from these low-biomass microbial communities, the optimal sampling strategy for characterizing murine lung microbiota has not been empirically determined. Performing accurate, reliable characterization of murine lung microbiota and distinguishing true microbial signal from noise in these samples will be critical for further mechanistic microbiome studies in mice. RESULTS: Using an analytic approach grounded in microbial ecology, we compared bacterial DNA from the lungs of healthy adult mice collected via two common sampling approaches: homogenized whole lung tissue and bronchoalveolar lavage (BAL) fluid. We quantified bacterial DNA using droplet digital PCR, characterized bacterial communities using 16S rRNA gene sequencing, and systematically assessed the quantity and identity of bacterial DNA in both specimen types. We compared bacteria detected in lung specimens to each other and to potential source communities: negative (background) control specimens and paired oral samples. By all measures, whole lung tissue in mice contained greater bacterial signal and less evidence of contamination than did BAL fluid. Relative to BAL fluid, whole lung tissue exhibited a greater quantity of bacterial DNA, distinct community composition, decreased sample-to-sample variation, and greater biological plausibility when compared to potential source communities. In contrast, bacteria detected in BAL fluid were minimally different from those of procedural, reagent, and sequencing controls. CONCLUSIONS: An ecology-based analytical approach discriminates signal from noise in this low-biomass microbiome study and identifies whole lung tissue as the preferred specimen type for murine lung microbiome studies. Sequencing, analysis, and reporting of potential source communities, including negative control specimens and contiguous biological sites, are crucial for biological interpretation of low-biomass microbiome studies, independent of specimen type. Video abstract.


Assuntos
Microbiota , Animais , Bactérias/genética , DNA Bacteriano/genética , Feminino , Pulmão , Camundongos , Microbiota/genética , Gravidez , RNA Ribossômico 16S/genética
16.
Front Immunol ; 12: 636198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841417

RESUMO

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26-30°C) - has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18-20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium via goblet cell antigen passages (GAPs). In contrast, food allergy sensitive Il4ra F709 mice housed under standard temperature conditions translocated the luminal antigens in the SI across the epithelium via secretory antigen passages (SAPs). Activation of SI antigen passages and oral challenge of Il4ra F709 mice with egg allergens at standard temperature predisposed Il4ra F709 mice to develop an anaphylactic reaction. Housing Il4ra F709 mice at Tn altered systemic type 2 cytokine, IL-4, and the landscape of SI antigen passage patterning (villus and crypt involvement). Activation of SI antigen passages and oral challenge of Il4ra F709 mice with egg antigen under Tn conditions led to the robust induction of egg-specific IgE and development of food-induced mast cell activation and hypovolemic shock. Similarly, Tn housing of WT BALB/c mice altered the cellular patterning of SI antigen passage (GAPs to SAPs). Activation of SI antigen passages and the oral challenge of WT BALB/c mice with egg antigen led to systemic reactivity to egg and mast cell activation. Together these data demonstrate that Tn housing alters antigen passage cellular patterning and landscape, and concurrent oral exposure of egg antigens and SAP activation is sufficient to induce oral antigen sensitization.


Assuntos
Alérgenos/metabolismo , Anafilaxia/metabolismo , Hipersensibilidade a Ovo/metabolismo , Proteínas do Ovo/metabolismo , Abrigo para Animais , Intestino Delgado/metabolismo , Temperatura , Administração Oral , Alérgenos/administração & dosagem , Alérgenos/imunologia , Anafilaxia/imunologia , Anafilaxia/microbiologia , Animais , Modelos Animais de Doenças , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/microbiologia , Proteínas do Ovo/administração & dosagem , Proteínas do Ovo/imunologia , Microbioma Gastrointestinal , Células Caliciformes/imunologia , Células Caliciformes/metabolismo , Células Caliciformes/microbiologia , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Permeabilidade , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo
17.
Neuroreport ; 32(5): 394-398, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33661810

RESUMO

One-third of the population in the UK and worldwide struggle with chronic pain. Entraining brain alpha activity through noninvasive visual stimulation has been shown to reduce experimental pain in healthy volunteers. Neural oscillations entrainment offers a potential noninvasive and nonpharmacological intervention for patients with chronic pain, which can be delivered in the home setting and has the potential to reduce use of medications. However, evidence supporting its use in patients with chronic pain is lacking. This study explores whether (a) alpha entrainment increase alpha power in patients and (b) whether this increase in alpha correlates with analgesia. In total, 28 patients with chronic pain sat in a comfortable position and underwent 4-min visual stimulation using customised goggles at 10 Hz (alpha) and 7 Hz (control) frequency blocks in a randomised cross-over design. 64-channel electroencephalography and 11-point numeric rating scale pain intensity and pain unpleasantness scores were recorded before and after stimulation. Electroencephalography analysis revealed frontal alpha power was significantly higher when stimulating at 10 Hz when compared to 7 Hz. There was a significant positive correlation between increased frontal alpha and reduction in pain intensity (r = 0.33; P < 0.05) and pain unpleasantness (r = 0.40; P < 0.05) in the 10 Hz block. This study provides the first proof of concept that changes in alpha power resulting from entrainment correlate with an analgesic response in patients with chronic pain. Further studies are warranted to investigate dose-response parameters and equivalence to analgesia provided by medications.


Assuntos
Ritmo alfa/fisiologia , Dor Crônica/terapia , Manejo da Dor/métodos , Percepção da Dor/fisiologia , Estimulação Luminosa/métodos , Adulto , Idoso , Dor Crônica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito
18.
Ann Am Thorac Soc ; 18(11): 1876-1885, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33577740

RESUMO

Rationale: Patients with severe coronavirus disease (COVID-19) meet clinical criteria for the acute respiratory distress syndrome (ARDS), yet early reports suggested they differ physiologically and clinically from patients with non-COVID-19 ARDS, prompting treatment recommendations that deviate from standard evidence-based practices for ARDS. Objectives: To compare respiratory physiology, clinical outcomes, and extrapulmonary clinical features of severe COVID-19 with non-COVID-19 ARDS. Methods: We performed a retrospective cohort study, comparing 130 consecutive mechanically ventilated patients with severe COVID-19 with 382 consecutive mechanically ventilated patients with non-COVID-19 ARDS. Initial respiratory physiology and 28-day outcomes were compared. Extrapulmonary manifestations (inflammation, extrapulmonary organ injury, and coagulation) were compared in an exploratory analysis. Results: Comparison of patients with COVID-19 and non-COVID-19 ARDS suggested small differences in respiratory compliance, ventilatory efficiency, and oxygenation. The 28-day mortality was 30% in patients with COVID-19 and 38% in patients with non-COVID-19 ARDS. In adjusted analysis, point estimates of differences in time to breathing unassisted at 28 days (adjusted subdistributional hazards ratio, 0.98 [95% confidence interval (CI), 0.77-1.26]) and 28-day mortality (risk ratio, 1.01 [95% CI, 0.72-1.42]) were small for COVID-19 versus non-COVID-19 ARDS, although the confidence intervals for these estimates include moderate differences. Patients with COVID-19 had lower neutrophil counts but did not differ in lymphocyte count or other measures of systemic inflammation. Conclusions: In this single-center cohort, we found no evidence for large differences between COVID-19 and non-COVID-19 ARDS. Many key clinical features of severe COVID-19 were similar to those of non-COVID-19 ARDS, including respiratory physiology and clinical outcomes, although our sample size precludes definitive conclusions. Further studies are needed to define COVID-19-specific pathophysiology before a deviation from evidence-based treatment practices can be recommended.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Respiração Artificial , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , SARS-CoV-2
19.
J Labelled Comp Radiopharm ; 64(1): 30-39, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33063888

RESUMO

Described here is a method for the measurement of the radio-metabolites of the positron emission tomography radiotracer [6-O-methyl-11 C]diprenorphine ([11 C]diprenorphine) using in-line solid-phase extraction (SPE) combined with radio-high-pressure liquid chromatography analysis. We believe that this method offers a reliable and reproducible approach to [11 C]diprenorphine metabolite analysis. In addition, different SPE stationary phases are assessed for their efficiency for loading, retention and elution of the parent molecule and its metabolites. Having assessed C4, phenyl and C18 stationary phase, we concluded that a C18 SPE was optimal for our method. Finally, in silico predictions of diprenorphine metabolism were compared with in vivo metabolism of [11 C]diprenorphine induced by hepatic microsomal digestion and analysed by matrix-assisted laser desorption/ionisation mass spectrometry. It was found that there was a high degree of agreement between the two methods and in particular the formation of the diprenorphine-3-glucuronide metabolite.


Assuntos
Cromatografia Líquida de Alta Pressão , Diprenorfina , Tomografia por Emissão de Pósitrons , Extração em Fase Sólida
20.
mSphere ; 5(6)2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208515

RESUMO

Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infections and continues to spread despite widespread implementation of pathogen-targeted control guidelines. Commensal gut microbiota provide colonization resistance to VRE, but the role of gut microbiota in VRE acquisition in at-risk patients is unknown. To address this gap in our understanding, we performed a case-control study of gut microbiota in hospitalized patients who did (cases) and did not (controls) acquire VRE. We matched case subjects to control subjects by known risk factors and "time at risk," defined as the time elapsed between admission until positive VRE screen. We characterized gut bacterial communities using 16S rRNA gene amplicon sequencing of rectal swab specimens. We analyzed 236 samples from 59 matched case-control pairs. At baseline, case and control subjects did not differ in gut microbiota when measured by community diversity (P = 0.33) or composition (P = 0.30). After hospitalization, gut communities of cases and controls differed only in the abundance of the Enterococcus-containing operational taxonomic unit (OTU), with the gut microbiota of case subjects having more of this OTU than time-matched control subjects (P = 0.01). Otherwise, case and control communities after the time at risk did not differ in diversity (P = 0.33) or community structure (P = 0.12). Among patients who became VRE colonized, those having the Blautia-containing OTU on admission had lower Enterococcus relative abundance once colonized (P = 0.004). Our results demonstrate that the 16S profile of the gut microbiome does not predict VRE acquisition in hospitalized patients, likely due to rapid and profound microbiota change. The gut microbiome does not predict VRE acquisition, but it may be associated with Enterococcus expansion, suggesting that these should be considered two distinct processes.IMPORTANCE The Centers for Disease Control and Prevention estimates that VRE causes an estimated 54,000 infections and 539 million dollars in attributable health care costs annually. Despite improvements in hand washing, environmental cleaning, and antibiotic use, VRE is still prevalent in many hospitals. There is a pressing need to better understand the processes by which patients acquire VRE. Multiple lines of evidence suggest that intestinal microbiota may help some patients resist VRE acquisition. In this large case-control study, we compared the 16S profile of intestinal microbiota on admission in patients that did and did not subsequently acquire VRE. The 16S profile did not predict subsequent VRE acquisition, in part due to rapid and dramatic change in the gut microbiome following hospitalization. However, Blautia spp. present on admission predicted decreased Enterococcus abundance after VRE acquisition, and Lactobacillus spp. present on admission predicted Enterococcus dominance after VRE acquisition. Thus, VRE acquisition and domination may be distinct processes.


Assuntos
Enterococcus faecium/crescimento & desenvolvimento , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/genética , Enterococos Resistentes à Vancomicina/crescimento & desenvolvimento , Antibacterianos/farmacologia , Fenômenos Fisiológicos Bacterianos , Estudos de Casos e Controles , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Enterococcus faecium/patogenicidade , Fezes/microbiologia , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Vancomicina/farmacologia , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/patogenicidade
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