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1.
PLoS One ; 18(2): e0280499, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36730255

RESUMO

E. coli Nissle (EcN) is a non-pathogenic probiotic bacterium of the Enterobacteriaceae family that has been used for over a century to promote general gut health. Despite the history of safe usage of EcN, concerns have been raised regarding the presence of the pks gene cluster, encoding the genotoxin colibactin, due to its association with colorectal cancer. Here, we sought to determine the effect of pks island removal on the in vitro and in vivo robustness and activity of EcN and EcN-derived strains. A deletion of the pks island (Δpks) was constructed in wild type and engineered strains of EcN using lambda red recombineering. Mass spectrometric measurement of N-myristoyl-D-asparagine, released during colibactin maturation, confirmed that the pks deletion abrogated colibactin production. Growth curves were comparable between Δpks strains and their isogenic parents, and wild type EcN displayed no competitive advantage to the Δpks strain in mixed culture. Deletion of pks also had no effect on the activity of strains engineered to degrade phenylalanine (SYNB1618 and SYNB1934) or oxalate (SYNB8802). Furthermore, 1:1 mixed dosing of wild type and Δpks EcN in preclinical mouse and nonhuman primate models demonstrated no competitive disadvantage for the Δpks strain with regards to transit time or colonization. Importantly, there was no significant difference on in vivo strain performance between the clinical-stage strain SYNB1934 and its isogenic Δpks variant with regards to recovery of the quantitative strain-specific biomarkers d5- trans-cinnamic acid, and d5-hippuric acid. Taken together, these data support that the pks island is dispensable for Synthetic Biotic fitness and activity in vivo and that its removal from engineered strains of EcN will not have a deleterious effect on strain efficacy.

2.
JMIR Serious Games ; 11: e38484, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626195

RESUMO

BACKGROUND: Replacing sedentary behaviors during leisure time with active video gaming has been shown to be an enjoyable option for increasing physical activity. However, most off-the-shelf active video gaming controllers are not accessible or usable for individuals with mobility impairments. To address this requirement, a universal video game controller (called the GAIMplank) was designed and developed. OBJECTIVE: This study aimed to assess the usability of the GAIMplank video game controller for playing PC video games among individuals with mobility impairments. Measures of enjoyment, perceived exertion, and qualitative data on the user experience were also examined. METHODS: Adults (aged 18-75 years) with a mobility impairment were recruited to participate in a single testing session in the laboratory. Before testing began, basic demographic information, along with minutes of weekday and weekend physical activity, minutes of weekday and weekend video game play, and video game play experience were collected. The GAIMplank was mapped to operate as a typical joystick controller. Depending on their comfort and functional ability, participants chose to play seated in a chair, standing, or in their own manual wheelchair. Leaning movements of the trunk created corresponding action in the game (ie, lean right to move right). The participants played a total of 5 preselected video games for approximately 5 minutes each. Data were collected to assess the usability of the GAIMplank, along with self-efficacy regarding execution of game play actions, rating of perceived exertion and enjoyment for each game, and overall qualitative feedback. RESULTS: A total of 21 adults (n=15, 71% men; n=6, 29% women) completed the usability testing, with a mean age of 48.8 (SD 13.8; range 21-73) years. Overall, 38% (8/21) of adults played while standing, 33% (7/21) of adults played while seated in a chair, and 29% (6/21) played in their own manual wheelchair. Scores from the System Usability Scale indicated above average (74.8, SD 14.5) usability, with scores best for those who played seated in a chair, followed by those standing, and then individuals who played seated in their own wheelchairs. Inconsistencies in the responsiveness of the controller and general feedback for minor improvements were documented. Rating of perceived exertion scores ranged from light to moderate intensity, with the highest scores for those who played seated in a chair. Participants rated their experience with playing each game from above average to very enjoyable. CONCLUSIONS: The GAIMplank video game controller was found to be usable and accessible, providing an enjoyable option for light-to-moderate intensity exercise among adults with mobility impairments. Minor issues with inconsistencies in controller responsiveness were also recorded. Following further development and refinement, the next phase will include a pilot exercise intervention using the GAIMplank system.

3.
Chemistry ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594445

RESUMO

A one-step method for the conversion of nitroarenes into phenols under operationally simple, transition-metal-free conditions is described. This denitrative functionalisation protocol provides a concise and economical alternative to conventional three-step synthetic sequences. Experimental and computational studies suggest that nitroarenes may be substituted via an electron-catalysed radical-nucleophilic substitution (SRN1) chain mechanism.

4.
Int J Surg Pathol ; : 10668969221142041, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514283

RESUMO

We report a case of a 65-year-old man with alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma that microscopically consisted of a polymorphous blend of enteroblastic, yolk sac-like, and hepatoid carcinoma components of variable proportions. No histological evidence of Barrett's esophagus was identified. Two weeks post-endoscopic mucosal mass resection, the serum AFP level was 1434.6 ng/mL. The patient underwent radiation and chemotherapy but developed metastatic lung lesions. At 18 months post-resection, the patient is alive. AFP-producing esophageal adenocarcinoma is a rare entity. We reviewed reported cases for clinicopathological features, treatment strategies, and prognosis.

5.
PLoS One ; 17(12): e0277023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36512555

RESUMO

Tinnitus is a complex and not yet fully understood phenomenon. Often the treatments provided are effective only for subgroups of sufferers. We are presently not able to predict benefit with the currently available diagnostic tools and analysis methods. Being able to identify and specifically treat sub-categories of tinnitus would help develop and implement more targeted treatments with higher success rate. In this study we use a clustering analysis based on 17 predictors to cluster an audiologically homogeneous group of normal hearing participants, both with and without tinnitus. The predictors have been chosen to be either tinnitus-specific measures or measures that are thought to be connected to cochlear synaptopathy. Our aim was to identify a subgroup of participants with characteristics consistent with the current hypothesized impact of cochlear synaptopathy. Our results show that this approach can separate the listeners into different clusters. But not in all cases could the tinnitus sufferers be separated from the control group. Another challenge is the use of categorical measures which seem to dominate the importance analysis of the factors. The study showed that data-driven clustering of a homogeneous listener group based on a mixed set of experimental outcome measures is a promising tool for tinnitus sub-typing, with the caveat that sample sizes might need to be sufficiently high, and higher than in the present study, to keep a meaningful sample size after clustering.


Assuntos
Zumbido , Humanos , Zumbido/diagnóstico , Audição , Cóclea , Testes Auditivos
6.
Breathe (Sheff) ; 18(1): 220015, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36338248

RESUMO

Intravenous magnesium sulphate allows safer intravenous ß2-agonist delivery in acute-severe and life-threatening asthma attacks https://bit.ly/3veUpfC.

7.
J Intensive Care Med ; : 8850666221139223, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445019

RESUMO

Objectives: Describe contemporary ECMO utilization patterns among patients with traumatic brain injury (TBI) and examine clinical outcomes among TBI patients requiring ECMO. Design: Retrospective cohort study. Setting: Premier Healthcare Database (PHD) between January 2016 to June 2020. Subjects: Adult patients with TBI who were mechanically ventilated and stratified by exposure to ECMO. Results: Among patients exposed to ECMO, we examined the following clinical outcomes: hospital LOS, ICU LOS, duration of mechanical ventilation, and hospital mortality. Of our initial cohort (n = 59,612), 118 patients (0.2%) were placed on ECMO during hospitalization. Most patients were placed on ECMO within the first 2 days of admission (54.3%). Factors associated with ECMO utilization included younger age (OR 0.96, 95% CI (0.95-0.97)), higher injury severity score (ISS) (OR 1.03, 95% CI (1.01-1.04)), vasopressor utilization (2.92, 95% CI (1.90-4.48)), tranexamic acid utilization (OR 1.84, 95% CI (1.12-3.04)), baseline comorbidities (OR 1.06, 95% CI (1.03-1.09)), and care in a teaching hospital (OR 3.04, 95% CI 1.31-7.05). A moderate degree (ICC = 19.5%) of variation in ECMO use was explained at the individual hospital level. Patients exposed to ECMO had longer median (IQR) hospital and ICU length of stay (LOS) [26 days (11-36) versus 9 days (4-8) and 19.5 days (8-32) versus 5 days (2-11), respectively] and a longer median (IQR) duration of mechanical ventilation [18 days (8-31) versus 3 days (2-8)]. Patients exposed to ECMO experienced a hospital mortality rate of 33.9%, compared to 21.2% of TBI patients unexposed to ECMO. Conclusions: ECMO utilization in mechanically ventilated patients with TBI is rare, with significant variation across hospitals. The impact of ECMO on healthcare utilization and hospital mortality following TBI is comparable to non-TBI conditions requiring ECMO. Further research is necessary to better understand the role of ECMO following TBI and identify patients who may benefit from this therapy.

8.
JCI Insight ; 7(23)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36256481

RESUMO

High endothelial venule protein/SPARC-like 1 (hevin/Sparcl1) is an astrocyte-secreted protein that regulates synapse formation in the brain. Here we show that astrocytic hevin signaling plays a critical role in maintaining chronic pain. Compared with WT mice, hevin-null mice exhibited normal mechanical and heat sensitivity but reduced inflammatory pain. Interestingly, hevin-null mice have faster recovery than WT mice from neuropathic pain after nerve injury. Intrathecal injection of WT hevin was sufficient to induce persistent mechanical allodynia in naive mice. In hevin-null mice with nerve injury, adeno-associated-virus-mediated (AAV-mediated) re-expression of hevin in glial fibrillary acidic protein-expressing (GFAP-expressing) spinal cord astrocytes could reinstate neuropathic pain. Mechanistically, hevin is crucial for spinal cord NMDA receptor (NMDAR) signaling. Hevin-potentiated N-Methyl-D-aspartic acid (NMDA) currents are mediated by GluN2B-containing NMDARs. Furthermore, intrathecal injection of a neutralizing Ab against hevin alleviated acute and persistent inflammatory pain, postoperative pain, and neuropathic pain. Secreted hevin that was detected in mouse cerebrospinal fluid (CSF) and nerve injury significantly increased CSF hevin abundance. Finally, neurosurgery caused rapid and substantial increases in SPARCL1/HEVIN levels in human CSF. Collectively, our findings support a critical role of hevin and astrocytes in the maintenance of chronic pain. Neutralizing of secreted hevin with monoclonal Ab may provide a new therapeutic strategy for treating acute and chronic pain and NMDAR-medicated neurodegeneration.

9.
JMIR Pediatr Parent ; 5(3): e38297, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36103216

RESUMO

BACKGROUND: Human Papillomavirus (HPV) vaccination is recommended for children aged 11-12 years in the United States. One factor that may contribute to low national HPV vaccine uptake is parental exposure to misinformation on social media. OBJECTIVE: This study aimed to examine the association between parents' perceptions of the HPV vaccine information on social media and internet verification strategies used with the HPV vaccine decision-making stage for their child. METHODS: Parents of children and adolescents aged 9-17 years were recruited for a cross-sectional survey in North Texas (n=1192) and classified into 3 groups: children and adolescents who (1) were vaccinated, (2) unvaccinated and did not want the vaccine, and (3) unvaccinated and wanted the vaccine. Multinomial logistic regression models were estimated to identify factors associated with the HPV vaccine decision-making stage with children and adolescents who were vaccinated as the referent group. RESULTS: Of the 1192 respondents, 44.7% (n=533) had an HPV-vaccinated child, 38.8% (n=463) had an unvaccinated child and did not want the vaccine, and 16.4% (n=196) had an unvaccinated child and wanted the vaccine. Respondents were less likely to be "undecided/not wanting the vaccine" if they agreed that HPV information on social media is credible (adjusted odds ratio [aOR] 0.40, 95% CI 0.26-0.60; P=.001), disagreed that social media makes them question the HPV vaccine (aOR 0.22, 95% CI 0.15-0.33; P<.001), or had a higher internet verification score (aOR 0.74, 95% CI 0.62-0.88; P<.001). CONCLUSIONS: Interventions that promote web-based health literacy skills are needed so parents can protect their families from misinformation and make informed health care decisions.

10.
Neurosci Lett ; 787: 136822, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-35934164

RESUMO

Failure to translate promising potential therapeutics for intracerebral hemorrhage (ICH) partially results from limited understanding of cellular mechanisms underlying brain injury and repair. Understanding neural repair mechanisms after brain injury requires intricate comprehension of microglial behavior; however, studying individual microglial cell behavior is challenging. Further single cell isolation techniques may be an excellent means to expand known differences in male and female microglial cell response to ICH. In this study, 24 h after intrastriatal collagenase injection, one male and one female CX3CR1-GFP mouse underwent ex vivo microglial cell isolation via micropipette from perihematomal regions and equivalent location of contralateral striata. After cell collection, individual and grouped cell samples underwent reverse transcription and analyses for gene expression using Fluidigm RT-PCR technology. Data were analyzed by t-tests and visualized as a heatmap of the log2 Ct values. Gene expression assays were chosen for target-specific amplification, including markers of M1 pro-inflammatory microglial phenotype (i.e., Tnf, Il6, Fcgr3/CD16), M2 anti-inflammatory markers (i.e., Mrc1/CD206, Arg1, Tgfb1), and genes involved in the toll-like receptor pathway (i.e., Tlr2, Tlr4 and Myd88). Greater number of individual microglia cells expressed Mcr1, Tlr2, and Arg1 in perihematomal tissue than in contralateral hemispheres. Additionally, more male microglia expressed Myd88, Tlr2, Il6, and Arg1 than did female microglia. Single cell microglial isolation is feasible after in vivo rodent ICH. Differential gene expression can be detected between individual cells from different brain regions and experimental conditions. Cell-specific analyses will contribute to improved understanding of microglial roles in both post-ICH pathogenesis and recovery.


Assuntos
Lesões Encefálicas , Microglia , Animais , Lesões Encefálicas/metabolismo , Separação Celular , Hemorragia Cerebral/metabolismo , Feminino , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 2 Toll-Like
11.
Viruses ; 14(8)2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36016428

RESUMO

BACKGROUND AND AIMS: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17ß-oestradiol controls HCV's life cycle. We investigated the mechanism(s) behind oestrogen's antiviral effect. METHODS: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17ß-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. RESULTS: Stimulation of 17ß-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. CONCLUSION: Resulting in viral control and suppression, 17ß-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling.


Assuntos
Hepatite C , Interferon Tipo I , Antivirais/uso terapêutico , Estradiol/metabolismo , Estradiol/farmacologia , Estradiol/uso terapêutico , Estrogênios/metabolismo , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Feminino , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatócitos/metabolismo , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Interferon-alfa/farmacologia , Masculino , Replicação Viral
12.
ACS Sustain Chem Eng ; 10(27): 8846-8855, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35846798

RESUMO

The surfactant market represents a key sector of the chemical industry and encompasses many diverse applications. Their sustainability in terms of feedstock used, synthetic procedure, biodegradability, and formulation are crucial parameters to assessing the environmental impact of the surfactant. The anionic surfactant linear alkyl benzene sulfonates have proven successful to date because of their high performance, low cost, and extensive studies within formulations to optimize performance, allowing usage in a large variety of applications, especially in cleaning. Due to their advantageous properties and extensive research and development, their substitution with a biobased surfactant such as sodium dodecyl sulfate has struggled to succeed. Furan surfactants have been reported as valuable candidates for the implementation of green alternatives to traditional anionic sulfonated surfactants with a perfect trade-off between performances and green credentials. However, their implementation suffers of scalability and high cost in producing the final product due to feedstock availability and low yields of the final product. Herein, we report a new class of furan surfactants, sulfonated alkyl furoates, which are derived from the esterification of furoic acid and fatty alcohols, followed by a sulfonation step. Compared to traditional surfactants, they showed more favorable behavior in basic proprieties (such as critical micelle concentration, ecotoxicity, hard water resistance, surface tension water/oil), which gives a good prospective for the introduction of a new biobased chemical with superior performances.

13.
Ann Med ; 54(1): 2123-2136, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35900132

RESUMO

Adolescence is a developmental stage defined in part by risk-taking. Risk-taking is critical to normal development and has important benefits including trying new activities and exploring new relationships. Risk-taking is also associated with the initiation of substance use. Because substance use often begins in adolescence, much focus has been on primary prevention with the goal of preventing initial substance use. Secondary or tertiary prevention approaches, such as counselling to eliminate substance use or offering treatment, are common approaches for adolescents with problematic substance use or a substance use disorder. While this is important, for some adolescents, treatment or cessation of use may not be desired. In these cases, Healthcare Practitioners (HCPs) can offer clear advice that incorporates harm reduction. Harm reduction, which is often applied for adults who use substances, reduces the negative impacts associated with drug use without requiring abstinence. Harm reduction is crucial to keeping adolescents safe and healthy and can offer opportunities for future engagement in treatment. The objective of this review is to describe strategies for integrating harm reduction principles in clinical settings that are developmentally appropriate. A patient-centered, harm reduction approach can validate perceived benefits of substance use, offer strategies to minimise harm, and advise reduction of use and abstinence.KEY MESSAGES:Substance use often begins in adolescence and traditional approaches are often rooted in prevention framework.Harm reduction should be incorporated for adolescents with problematic substance use or a substance use disorder.This review offers strategies for integration of harm reduction principles tailored towards adolescents.


Assuntos
Redução do Dano , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Humanos , Saúde Pública , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
14.
Adv Exp Med Biol ; 1370: 369-379, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35882811

RESUMO

Taurine plays an important role in neural growth and function from early to adult life, particularly in learning and memory via BDNF action. This study tested the hypothesis that BDNF differentially potentiates entorhinal-hippocampal synaptic transmission in vivo in adult rats. In anesthetized male Sprague-Dawley rats, a stainless steel recording electrode with an attached microinjector was placed into CA1 and the dentate gyrus to record fEPSP, and a paired stainless steel electrode was inserted into entorhinal cortex for continuous paired-pulse stimulation of that brain region. In the dentate gyrus, microinjection of BDNF resulted in a gradual increase in the peak slope of the fEPSP. Following the infusion, the peak fEPSP began to rise in about 8 min, reached a maximum of 120 ± 2% (from baseline) by about 20 min, and remained near peak elevation (~115%) for more than 30 min. In contrast, the same dose of BDNF when injected into CA1 had no consistent effect on fEPSP slopes in the CA1. Further, an equimolar cytochrome C (horse heart) infusion had no significant effect on fEPSP slopes in either the dentate gyrus or CA1. The potentiation effect of BDNF in the dentate gyrus is consistent with a significant increase in power spectral density of dentate gyrus field potentials at 70-200 Hz, but not at frequencies below 70 Hz. In addition, the CA1 power spectral density was not affected by BDNF (compared to cytochrome C). These data indicate that in vivo BDNF potentiates entorhinal-hippocampal synaptic transmission in dentate gyrus, but not in CA1.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Giro Denteado , Animais , Citocromos c/farmacologia , Giro Denteado/fisiologia , Cavalos , Masculino , Memória , Testes de Memória e Aprendizagem , Ratos , Ratos Sprague-Dawley , Aço Inoxidável/farmacologia , Taurina/farmacologia
15.
J Orthod ; 49(4): 412-419, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35796491

RESUMO

OBJECTIVE: To apply an automated computerised method to categorise and determine the prevalence of different types of lip traits, and to explore associations between lip traits and sex differences. DESIGN: Observational descriptive study utilising an automated method of facial assessment. SETTING AND PARTICIPANTS: A total of 4747 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who each had 3D facial scans carried out at 15 years of age. METHODS: Each of the participants was automatically categorised regarding predetermined lip morphological traits. Descriptive statistics were applied to report the prevalence of the different types of each trait, and chi-square tests were used to investigate sex differences and associations between traits. RESULTS: A total of 4730 individuals were assessed (47% male, 53% female). Eight predetermined lip traits have been reported previously. There were differences in prevalence for all lip traits in male and female patients (all P ⩽ 0.0002), with differences between the sexes described for each trait. For example, a deeply grooved philtrum of average width was more prevalent in boys, and an indentation near the upper vermilion border was more prevalent in girls. Each of the traits was significantly associated with the other traits (all P < 0.0001), with particularly strong associations seen between traits in the same region (e.g. upper lip). Individual associations between traits are reported; for example, a straight lip contour was found to be associated with no true vermilion border in both the upper and lower lip regions. CONCLUSION: The automated computerised method described is an invaluable tool for the categorisation of lip morphological traits. The prevalence of various types of traits has been described. Sexual dimorphism exists for all the lip traits assessed. Generally, each of the traits are associated with all other traits, with individual associations reported.


Assuntos
Face , Lábio , Humanos , Criança , Feminino , Masculino , Lábio/anatomia & histologia , Estudos Longitudinais , Face/anatomia & histologia , Caracteres Sexuais , Fenótipo , Cefalometria/métodos
16.
Can J Anaesth ; 69(9): 1139-1150, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35819630

RESUMO

PURPOSE: Peripheral nerve blocks improve analgesia following hip fracture; however, there are little published data on safety and outcomes of continuous regional anesthetic techniques. Our institution offers pre- and perioperative, anesthesiologist-delivered ultrasound-guided suprainguinal fascia iliaca catheters (FICs) to patients with hip fracture. We aimed to document the safety profile of this technique and establish whether there are any significant clinical benefits in outcomes measured by the UK National Hip Fracture Database. METHODS: We performed a single-centre historical cohort study of 2,187 patients admitted to our institution with hip fracture over a 5.75-year period. Of these, 915 were treated with FIC and 1,272 received standard care (single-shot block). To control for baseline differences between these two cohorts, we used propensity score matching and exact matching, resulting in two well-matched groups of 728 patients treated with an FIC and standard care. RESULTS: No serious complications were observed as a result of an FIC. Unplanned removal occurred in 146/852 (17.1%) patients with documented data. No differences in 30-day mortality, pressure ulcer rates, or hospital length of stay were observed between the matched groups. The percentage of patients who were discharged to their usual residence was 79.3% in the FIC cohort vs 75.1% in the standard care cohort (difference, 4.2%; 95% confidence interval, -0.1 to 8.4; P = 0.06). DISCUSSION: Our single-centre propensity-matched historical cohort study suggests that ultrasound-guided suprainguinal fascia iliaca catheterization is a safe technique for patients with hip fracture and that our service is deliverable and sustainable within the UK's National Health Service. This study did not show statistically significant differences in outcomes between patients treated with FIC and standard care. An adequately powered multicentre randomized controlled trial comparing these approaches is warranted.


RéSUMé: OBJECTIF: Les blocs nerveux périphériques améliorent l'analgésie après une fracture de la hanche; cependant, il existe peu de données publiées sur l'innocuité et les devenirs des techniques d'anesthésie régionale continue. Notre établissement propose des cathéters iliofasciaux suprainguinaux échoguidés pré- et périopératoires aux patients souffrant d'une fracture de la hanche. Notre objectif était de documenter le profil d'innocuité de cette technique et de déterminer s'il existe des avantages cliniques significatifs au niveau des devenirs tels que mesurés par la Base de données nationale sur les fractures de la hanche du Royaume-Uni. MéTHODE: Nous avons réalisé une étude de cohorte historique monocentrique portant sur 2187 patients admis dans notre établissement avec une fracture de la hanche sur une période de 5,75 ans. De ce nombre, 915 ont été traités avec un cathéter iliofascial et 1272 ont reçu des soins standard (bloc à injection unique). Pour tenir compte des différences initiales entre ces deux cohortes, nous avons utilisé l'appariement par score de propension et l'appariement exact, ce qui a donné deux groupes bien appariés de 728 patients chaque, les patients étant traités par cathéter ilio-fascial ou soins standard. RéSULTATS: Aucune complication grave n'a été observée à la suite de l'utilisation d'un cathéter iliofascial. Un retrait imprévu est survenu chez 146/852 (17,1 %) patients dont les données ont été documentées. Aucune différence dans la mortalité à 30 jours, les taux d'escarres ou la durée de séjour à l'hôpital n'a été observée entre les groupes appariés. Le pourcentage de patients qui ont reçu leur congé à leur résidence habituelle était de 79,3 % dans la cohorte cathéter iliofascial vs 75,1 % dans la cohorte de soins standard (différence, 4,2 %; intervalle de confiance à 95 %, -0,1 à 8,4; P = 0,06). DISCUSSION: Notre étude de cohorte historique monocentrique et appariée par propension suggère que le cathétérisme iliofascial suprainguinal échoguidé est une technique sécuritaire pour les patients atteints de fracture de la hanche et que notre service est utilisable et durable au sein du National Health Service du Royaume-Uni. Cette étude n'a pas montré de différences statistiquement significatives dans les devenirs entre les patients traités par cathéter iliofascial ou par soins standard. Une étude randomisée contrôlée multicentrique suffisamment puissante comparant ces approches est justifiée.


Assuntos
Fraturas do Quadril , Bloqueio Nervoso , Cateteres , Estudos de Coortes , Fáscia , Fraturas do Quadril/cirurgia , Humanos , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória , Medicina Estatal , Ultrassonografia de Intervenção
17.
Front Immunol ; 13: 788935, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720395

RESUMO

Background: Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP. Methods: Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student's t-test. Results: Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion. Conclusions: Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.


Assuntos
Transplante de Fígado , Citocinas , Humanos , Fígado , Doadores Vivos , Preservação de Órgãos , Perfusão
18.
J Orthod ; 49(4): 403-411, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35723071

RESUMO

OBJECTIVE: To determine whether maternal smoking and/or alcohol consumption has an influence on lip morphology. Maternal smoking is a known risk factor for orofacial clefts; however, its influence on normal lip variation is unknown. Recent research regarding normal lip morphology has been contradictory. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 4747 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who each had 3D facial scans carried out at 15 years of age were included in the study. METHODS: Each of the participants was automatically categorised regarding predetermined lip morphological traits. Questionnaires completed by their mothers identified smoking and alcohol habits during pregnancy. Logistic regression analyses were applied to determine the effect of maternal smoking and alcohol consumption on lip morphology. RESULTS: Maternal smoking has significant effects on upper and lower lip contours, Cupid's bow, lower lip-chin shape and lower lip tone (all P < 0.05). There was also an indication of a potential epigenetic effect of smoking pre-pregnancy on upper lip contour (P = 0.0573). Alcohol consumption is significantly associated with philtrum shape, particularly when >6 units of alcohol are consumed per week (P = 0.0149, 32 weeks). Overall results suggest a deeply grooved philtrum is more likely if alcohol is consumed. Investigating the combined effect of smoking and alcohol consumption, lower lip contour (P = 0.00923) and lower lip-chin shape (P = 0.0171) are statistically significant, with lower lip contour more likely to be narrow in the midline, and lower lip-chin shape more likely to be an angular concavity. CONCLUSION: Maternal smoking influences a number of lip traits, including a possible epigenetic effect on upper lip contour. Maternal alcohol consumption, particularly at a high level, influences philtrum shape. Maternal smoking and alcohol consumption have a combined effect on lower lip contour and lower lip-chin shape.


Assuntos
Fenda Labial , Fissura Palatina , Humanos , Criança , Gravidez , Feminino , Fenda Labial/etiologia , Fissura Palatina/complicações , Fumar , Estudos Longitudinais , Estudos Retrospectivos , Consumo de Bebidas Alcoólicas , Etanol
19.
Head Neck ; 44(10): 2095-2108, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35708157

RESUMO

BACKGROUND: The relative incidence of laryngeal cancer is rising in young patients, yet their characteristics, risk factors, and outcomes relative to older patients are poorly understood. METHODS: Retrospective cohort analysis of the National Cancer Database from 2006 to 2015. RESULTS: Among 25 029 total patients, 923 (3.7%) were young (<45 years old) and 3266 underwent tumor HPV testing. Compared to older patients, a greater proportion of young patients were female (30.3%, 23.3%; p < 0.001) and seen with high-risk HPV-positive tumors (29.9%, 12.4%; p < 0.001). In subset analyses of young patients, females with higher income (≥$38 000) exhibited a decreased risk of overall mortality compared to all other sex-income subcategories (adjusted hazard ratio [aHR]: 0.43, 95% confidence interval [CI]: 0.25-0.72). In subset analyses of patients of all ages with known tumor HPV status, patients with high-risk HPV-positive tumors exhibited a reduced risk of all-cause mortality (aHR: 0.74, 95%CI: 0.60-0.92, p = 0.007). CONCLUSION: The interdependent associations between age, sex, tumor HPV status, and income on laryngeal cancer outcomes warrant further investigation.


Assuntos
Neoplasias Laríngeas , Infecções por Papillomavirus , Estudos de Coortes , Feminino , Hospitais , Humanos , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/terapia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Estudos Retrospectivos
20.
J Stroke Cerebrovasc Dis ; 31(8): 106600, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35728356

RESUMO

OBJECTIVE: To identify biomarkers with potential to indicate severity of perihematomal edema and secondary tissue injury after intracerebral hemorrhage (ICH), and which could be used as surrogate markers in future clinical trials for novel ICH therapeutics. MATERIALS AND METHODS: This exploratory cohort study compared trends in neuroinflammatory biomarker levels in 18 consecutively enrolled patients with acute supratentorial ICH and 16 patients treated with the investigational neuroprotective therapy CN-105 to identify a panel of 10 biomarkers. Biomarker levels over five days post-hemorrhage were then compared with edema volumes in a larger sample of patients treated with CN-105. RESULTS: Mean normalized edema volumes increased over time; higher CRP levels were associated with increased edema volumes (p = 0.006, r = 0.56). Higher IL8, IL10, MCP, and MMP-9 levels were associated with decreased edema volumes (p = 0.005, r =-0.57; p = 0.02, r =-0.51; p = 0.02, r =-0.52; p = .002, r =-0.63, respectively). IL1-RA, IL1-B, IL23, vWF, and IL17 levels were not significantly associated with edema volumes (p > 0.05). CONCLUSIONS: This exploratory study provides some of the first insights into the longitudinal associations between markers of neuroinflammation and development of perihematomal edema and secondary tissue injury in human ICH. We hypothesize that these biomarkers could be used as surrogates for treatment effect in novel therapies intended to limit neuroinflammation after ICH.


Assuntos
Edema Encefálico , Biomarcadores , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/tratamento farmacológico , Estudos de Coortes , Edema/diagnóstico , Edema/etiologia , Hematoma/complicações , Hematoma/etiologia , Humanos
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