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1.
Behav Brain Res ; 440: 114262, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36529299

RESUMO

Psilocybin and its active metabolite psilocin are hallucinogenic serotonergic agonists with high affinity for several serotonin receptors. In addition to underlying the hallucinogenic effects of these compounds, serotonin receptor activation also has important effects on decision-making and goal-directed behaviors. The impact of psilocybin and psilocin on these cognitive systems, however, remains unclear. This study investigated the effects of psilocybin treatment on decision-making and motivation in healthy male and female rats. We compared probability and delay discounting performance of psilocybin treated (1 mg/kg) to vehicle rats (n = 10/sex/group), and further assessed motivation in each group using a progressive ratio task. We also confirmed drug action by assessing head twitch responses after psilocybin treatment (1 mg/kg). Results from this study demonstrated that exposure to 1 mg/kg psilocybin did not affect decision-making in the probability and delay discounting tasks and did not reduce response rates in the progressive ratio task. However, psilocybin treatment did cause the expected increase in head twitch responses in both male and female rats, demonstrating that the drug was delivered at a pharmacologically relevant dosage. Combined, these results suggest that psilocybin may not impair or improve decision-making and motivation. Considering recent interest in psilocybin as a potential fast-acting therapeutic for a variety of mental health disorders, our findings also suggest the therapeutic effects of this drug may not be mediated by changes to the brain systems underlying reward and decision-making. Finally, these results may have important implications regarding the relative safety of this compound, suggesting that widespread cognitive impairments may not be seen in subjects, even after chronic treatment.


Assuntos
Alucinógenos , Psilocibina , Ratos , Masculino , Feminino , Animais , Psilocibina/farmacologia , Alucinógenos/farmacologia , Motivação , Encéfalo/metabolismo , Serotonina/farmacologia , Receptores de Serotonina/metabolismo
3.
Sci Rep ; 12(1): 18936, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344613

RESUMO

Poorly controlled cardiometabolic biometric health gap measures [e.g.,uncontrolled blood pressure (BP), HbA1c, and low-density lipoprotein cholesterol (LDL-C)] are mediated by medication adherence and clinician-level therapeutic inertia (TI). The study of comparing relative contribution of these two factors to disease control is lacking. We conducted a retrospective cohort study using 7 years of longitudinal electronic health records (EHR) from primary care cardiometabolic patients who were 35 years or older. Cox-regression modeling was applied to estimate how baseline proportion of days covered (PDC) and TI were associated with cardiometabolic related health gap closure. 92,766 patients were included in the analysis, among which 89.9%, 85.8%, and 73.3% closed a BP, HbA1c, or LDL-C gap, respectively, with median days to gap closure ranging from 223 to 408 days. Patients who did not retrieve a medication were the least likely to achieve biometric control, particularly for LDL-C (HR = 0.58, 95% CI: 0.55-0.60). TI or uncertainty of TI was associated with a high risk of health gap persistence, particularly for LDL-C (HR ranges 0.46-0.48). Both poor medication adherence and TI are independently associated with persistent health gaps, and TI has a much higher impact on disease control compared to medication adherence, implying disease management strategies should prioritize reducing TI.


Assuntos
Doenças Cardiovasculares , Adesão à Medicação , Humanos , LDL-Colesterol , Estudos Retrospectivos , Doenças Cardiovasculares/tratamento farmacológico
4.
Musculoskelet Surg ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445531

RESUMO

BACKGROUND: The glenohumeral joint dislocation can be associated with major nerve injury. The reported prevalence and risk factors for major nerve injury are variable and this injury can have a severe and life-long impact on the patient. The objectives of this study were to analyse the prevalence of major nerve injury following shoulder dislocation and examine risk factors. Management and outcomes of nerve injury were explored. METHODS: A 1 year retrospective cohort study of 243 consecutive adults who presented with a shoulder dislocation was performed. Data were collected on patient demographics, timings of investigations, treatment, follow-up, and nerve injury prevalence and management. The primary outcome measure was prevalence of nerve injury. Risk factors for this were analysed using appropriate tests with Stata SE15.1. RESULTS: Of 243 patients with shoulder dislocation, 14 (6%) had neurological deficit. Primary dislocation (p = 0.004) and older age (p = 0.02) were significantly associated with major nerve injury. Sex, time to successful reduction and force of injury were not associated with major nerve injury in this cohort. Patients with nerve injury made functional recovery to varying degrees. Recurrent shoulder dislocation was common accounting for 133/243 (55%) attendances. CONCLUSIONS: Shoulder dislocation requires careful assessment and timely management in the ED. A 6% rate of nerve injury following shoulder dislocation was at the lower border of reported rates (5-55%), and primary dislocation and older age were identified as risk factors for nerve injury. We emphasise the importance of referring patients with suspected major nerve injury to specialist services.

5.
Pharmacol Biochem Behav ; 221: 173482, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36244527

RESUMO

BACKGROUND: People who have co-occurring Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) carry a higher risk of adverse outcomes, including drug overdose. Early clinical and preclinical studies suggested that gabapentin may be effective in treating both disorders. The present study was designed to assess the effects of gabapentin on the subjective and physiological effects of oxycodone (OXY) and alcohol (ALC), alone and in combination. METHODS: During an 8-week, inpatient, within-subject, randomized, double-blind, placebo-controlled crossover study, non-treatment seeking participants (N = 13; 12 M/1F; 44.1 ± 3 years of age) with OUD and AUD were maintained on oral morphine (120 mg daily). Under gabapentin (1800 mg/day) and placebo (0 mg/day) maintenance, participants completed nine separate test sessions (three sessions per week) during which they received an oral solution containing 0, 15, or 30 mg/70 kg OXY in combination with 0, 0.5, or 0.75 g/kg ALC. During test sessions, subjective effects and physiological responses were assessed repeatedly on 100-mm visual analog scales (VAS). The primary outcome variable was the VAS rating of drug liking after receiving the drug challenge. RESULTS: Alcohol alone (but not oxycodone alone) produced dose-related increases in several positive subjective responses, including drug liking. Gabapentin significantly increased drug liking when given in combination with ALC and OXY + ALC (p < 0.05). Gabapentin did not clinically compromise respiration or other vital functions. CONCLUSIONS: Gabapentin may increase the abuse liability of ALC and OXY + ALC in those with co-occurring OUD and AUD.


Assuntos
Alcoolismo , Transtornos Relacionados ao Uso de Opioides , Humanos , Oxicodona/efeitos adversos , Analgésicos Opioides/efeitos adversos , Gabapentina , Alcoolismo/complicações , Alcoolismo/tratamento farmacológico , Estudos Cross-Over , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Etanol , Método Duplo-Cego
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 3830-3833, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086069

RESUMO

The healing of bone fractures is a complex and well-orchestrated physiological process, but normal healing is compromised when the fracture is large. These large non-union fractures often require a template with surgical intervention for healing. The standard treatment, autografting, has drawbacks such as donor site pain and limited availability. Biodegradable scaffolds developed using biomaterials such as bioactive glass are a potential solution. Investigation of bone ingrowth into biodegradable scaffolds is an important aspect of their development. Micro-CT (µ-CT) imaging is widely used to evaluate and quantify tissue ingrowth into scaffolds in 3D. Existing segmentation techniques have low accuracy in differentiating bone and scaffold, and need improvements to accurately quantify the bone in-growth into the scaffold using µ-CT scans. This study proposes a novel 3-stage pipeline for better outcome. The first stage of the pipeline is based on a convolutional neural network for the segmentation of the scaffold, bone, and pores from µ-CT images to investigate bone ingrowth. A 3D rigid image registration procedure was employed in the next stage to extract the volume of interest (VOI) for the analysis. In the final stage, algorithms were developed to quantitatively analyze bone ingrowth and scaffold degradation. The best model for segmentation produced a dice similarity coefficient score of 90.1, intersection over union score of 83.9, and pixel accuracy of 93.1 for unseen test data.


Assuntos
Osso e Ossos , Semântica , Materiais Biocompatíveis , Osso e Ossos/diagnóstico por imagem , Cicatrização , Microtomografia por Raio-X/métodos
8.
NPJ Breast Cancer ; 8(1): 109, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127361

RESUMO

Women with ductal carcinoma in situ (DCIS) have an increased risk of progression to invasive breast cancer. Although not all women with DCIS will progress to invasion, all are treated as such, emphasising the need to identify prognostic biomarkers. We have previously shown that altered myoepithelial cells in DCIS predict disease progression and recurrence. By analysing DCIS duct size in sections of human breast tumour samples, we identified an associated upregulation of integrin ß6 and an increase in periductal fibronectin deposition with increased DCIS duct size that associated with the progression of DCIS to invasion. Our modelling of the mechanical stretching myoepithelial cells undergo during DCIS progression confirmed the upregulation of integrin ß6 and fibronectin expression in isolated primary and cell line models of normal myoepithelial cells. Our studies reveal that this mechanostimulated DCIS myoepithelial cell phenotype enhances invasion in a TGFß-mediated upregulation of MMP13. Immunohistochemical analysis identified that MMP13 was specifically upregulated in DCIS, and it was associated with progression to invasion. These findings implicate tissue mechanics in altering the myoepithelial cell phenotype in DCIS, and that these alterations may be used to stratify DCIS patients into low and high risk for invasive progression.

9.
JMIR Med Inform ; 10(9): e38385, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066940

RESUMO

BACKGROUND: Electronic health record (EHR) systems are becoming increasingly complicated, leading to concerns about rising physician burnout, particularly for primary care physicians (PCPs). Managing the most common cardiometabolic chronic conditions by PCPs during a limited clinical time with a patient is challenging. OBJECTIVE: This study aimed to evaluate a Cardiometabolic Sutter Health Advanced Reengineered Encounter (CM-SHARE), a web-based application to visualize key EHR data, on the EHR use efficiency. METHODS: We developed algorithms to identify key clinic workflow measures (eg, total encounter time, total physician time in the examination room, and physician EHR time in the examination room) using audit data, and we validated and calibrated the measures with time-motion data. We used a pre-post parallel design to identify propensity score-matched CM-SHARE users (cases), nonusers (controls), and nested-matched patients. Cardiometabolic encounters from matched case and control patients were used for the workflow evaluation. Outcome measures were compared between the cases and controls. We applied this approach separately to both the CM-SHARE pilot and spread phases. RESULTS: Time-motion observation was conducted on 101 primary care encounters for 9 PCPs in 3 clinics. There was little difference (<0.8 minutes) between the audit data-derived workflow measures and the time-motion observation. Two key unobservable times from audit data, physician entry into and exiting the examination room, were imputed based on time-motion studies. CM-SHARE was launched with 6 pilot PCPs in April 2016. During the prestudy period (April 1, 2015, to April 1, 2016), 870 control patients with 2845 encounters were matched with 870 case patients and encounters, and 727 case patients with 852 encounters were matched with 727 control patients and 3754 encounters in the poststudy period (June 1, 2016, to June 30, 2017). Total encounter time was slightly shorter (mean -2.7, SD 1.4 minutes, 95% CI -4.7 to -0.9; mean -1.6, SD 1.1 minutes, 95% CI -3.2 to -0.1) for cases than controls for both periods. CM-SHARE saves physicians approximately 2 minutes EHR time in the examination room (mean -2.0, SD 1.3, 95% CI -3.4 to -0.9) compared with prestudy period and poststudy period controls (mean -1.9, SD 0.9, 95% CI -3.8 to -0.5). In the spread phase, 48 CM-SHARE spread PCPs were matched with 84 control PCPs and 1272 cases with 3412 control patients, having 1119 and 4240 encounters, respectively. A significant reduction in total encounter time for the CM-SHARE group was observed for short appointments (≤20 minutes; 5.3-minute reduction on average) only. Total physician EHR time was significantly reduced for both longer and shorter appointments (17%-33% reductions). CONCLUSIONS: Combining EHR audit log files and clinical information, our approach offers an innovative and scalable method and new measures that can be used to evaluate clinical EHR efficiency of digital tools used in clinical settings.

10.
Hydrobiologia ; : 1-21, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36065211

RESUMO

Monitoring the condition (water quality, biodiversity, hydromorphology) of small water bodies presents a challenge for the relevant authorities in terms of time and resources (labour and financial) due to the extensive length of the stream network or the sheer number of small standing water bodies. Citizen science can help address information gaps, but the effort required should not be underestimated if such projects are to generate reliable and sustained data collection. The overall aim of this paper is to propose a framework for operationalisation of citizen science targeting collection of data from small water bodies. We first consider the data gaps and the elements (water chemistry, ecology, hydromorphology) to be addressed, in order to define where citizen science could best make an impact. We review examples of tools and methods that are appropriate for small water bodies, based on experience from a selection of freshwater citizen science projects, and the support that is needed for effective and sustained small water body projects across Europe.

11.
Crit Rev Biotechnol ; : 1-16, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36001040

RESUMO

Hazardous airborne pollutants are frequently emitted to the atmosphere in the form of a gaseous mixture. Air biofilters as the primary biotechnological choice for waste gas treatment (low inlet concentration and high gas flow rate) should run properly when the feed contains multiple pollutants. Simultaneous removal of pollutants in biofilters has been extensively studied over the last 10 years. In this review, the results and findings of the mentioned studies including different groups of pollutants, such as methane (CH4) and volatile organic compounds (VOCs) are discussed. As the number of pollutants in a mixture increases, their elimination might become more complicated due to interactions between the pollutants. Parallel batch studies might be helpful to better understand these interaction effects in the absence of mass transfer limitations. Setting optimum operating conditions for removal of mixtures in biofilters is challenging because of opposing properties of pollutants. In biofilters, concerns, such as inlet gas composition variation and stability while dealing with abrupt inlet load and concentration changes, must be managed especially at industrial scales. Biofilters designed with multi-layer beds, allow tracking the fate of each pollutant as well as analyzing the diversity of microbial culture across the filter bed. Certain strategies are recommended to improve the performance of biofilters treating mixtures. For example, addition of (bio)surfactants as well as a second liquid phase in biotrickling filters might be considered for the elimination of multiple pollutants especially when hydrophobic pollutants are involved.

12.
JDR Clin Trans Res ; : 23800844221112062, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945823

RESUMO

INTRODUCTION: Edentulism affects health and quality of life. OBJECTIVES: Identify factors that predict older adults becoming edentulous over 12 y in the US Health and Retirement Study (HRS) by developing and validating a prediction model. METHODS: The HRS includes data on a representative sample of US adults aged >50 y. Selection criteria included participants in 2006 and 2018 who answered, "Have you lost all of your upper and lower natural permanent teeth?" Persons who answered "no" in 2006 and "yes" in 2018 experienced incident edentulism. Excluding 2006 edentulous, the data set (n = 4,288) was split into selection (70%, n = 3,002) and test data (30%, n = 1,286), and Monte Carlo cross-validation was applied to 500 random partitions of the selection data into training (n = 1,716) and validation (n = 1,286) data sets. Fitted logistic models from the training data sets were applied to the validation data sets to obtain area under the curve (AUC) for 32 candidate models. Six variables were included in all models (age, race/ethnicity, gender, education, smoking, last dental visit) while all combinations of 5 variables (income, alcohol use, self-rated health, loneliness, cognitive status) were considered for inclusion. The best parsimonious model based on highest mean AUC was fitted to the selection data set to obtain a final prediction equation. It was applied to the test data to estimate AUC and 95% confidence interval using 1,000 bootstrap samples. RESULTS: From 2006 to 2018, 9.7% of older adults became edentulous. The 2006 mean (SD) age was 66.7 (8.7) for newly edentulous and 66.3 (8.4) for dentate (P = 0.31). The baseline 6-variable model mean AUC was 0.740. The 7-variable model with cognition had AUC = 0.749 and test data AUC = 0.748 (95% confidence interval, 0.715-0.781), modestly improving prediction. Negligible improvement was gained from adding more variables. CONCLUSION: Cognition information improved the 12-y prediction of becoming edentulous beyond the modifiable risk factors of smoking and dental care use, as well as nonmodifiable demographic factors. KNOWLEDGE TRANSFER STATEMENT: This prediction modeling and validation study identifies cognition as well as modifiable (dental care use, smoking) and nonmodifiable factors (race, ethnicity, gender, age, education) associated with incident complete tooth loss in the United States. This information is useful for the public, dental care providers, and health policy makers in improving approaches to preventive care, oral and general health, and quality of life for older adults.

13.
Eur Arch Psychiatry Clin Neurosci ; 272(7): 1169-1181, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35802165

RESUMO

Deficits in social cognition and metacognition impact the course of psychosis. Sex differences in social cognition and metacognition could explain heterogeneity in psychosis. 174 (58 females) patients with first-episode psychosis completed a clinical, neuropsychological, social cognitive, and metacognitive assessment. Subsequent latent profile analysis split by sex yielded two clusters common to both sexes (a Homogeneous group, 53% and 79.3%, and an Indecisive group, 18.3% and 8.6% of males and females, respectively), a specific male profile characterized by presenting jumping to conclusions (28.7%) and a specific female profile characterized by cognitive biases (12.1%). Males and females in the homogeneous profile seem to have a more benign course of illness. Males with jumping to conclusions had more clinical symptoms and more neuropsychological deficits. Females with cognitive biases were younger and had lower self-esteem. These results suggest that males and females may benefit from specific targeted treatment and highlights the need to consider sex when planning interventions.


Assuntos
Transtornos Cognitivos , Metacognição , Transtornos Psicóticos , Cognição , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Transtornos Psicóticos/terapia , Cognição Social
14.
J Patient Exp ; 9: 23743735221113160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860789

RESUMO

The COVID-19 pandemic caused healthcare systems and patients to cancel or postpone healthcare services, particularly preventive care. Many patients still have not received these services raising concerns about the potential for preventable morbidity and mortality. At Sutter Health, a large integrated healthcare system in Northern California, we conducted a population-based email survey in August 2020 to evaluate perceptions and preferences about where, when, and how healthcare is delivered during the COVID-19 pandemic. In total, 3351 patients completed surveys, and 42.6% reported that they would "wait until they felt safe" before receiving a colonoscopy as compared to 22.4% for a mammogram. The doctor's office was the most common preferred location for receiving vaccines/shots (79.9%), though many also reported preferring an outdoor setting or in a car (63.7%). With over 40% of patients reporting that they would "wait until they feel safe" for a colonoscopy, healthcare systems could focus on promoting other evidence-based options such a fecal-occult blood test to ensure timely colon cancer screening.

15.
Nat Commun ; 13(1): 3810, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778387

RESUMO

Headwater streams are natural sources of methane but are suffering severe anthropogenic disturbance, particularly land use change and climate warming. The widespread intensification of agriculture since the 1940s has increased the export of fine sediments from land to streams, but systematic assessment of their effects on stream methane is lacking. Here we show that excess fine sediment delivery is widespread in UK streams (n = 236) and, set against a pre-1940s baseline, has markedly increased streambed organic matter (23 to 100 g m-2), amplified streambed methane production and ultimately tripled methane emissions (0.2 to 0.7 mmol CH4 m-2 d-1, n = 29). While streambed methane production responds strongly to organic matter, we estimate the effect of the approximate 0.7 °C of warming since the 1940s to be comparatively modest. By separating natural from human enhanced methane emissions we highlight how catchment management targeting the delivery of excess fine sediment could mitigate stream methane emissions by some 70%.


Assuntos
Metano , Rios , Agricultura , Sedimentos Geológicos , Humanos
16.
Mol Med Rep ; 26(2)2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35730624

RESUMO

Tumour hypoxia status provides prognostic information and predicts response to hypoxia­modifying treatments. A previous study by our group derived a 24­gene signature to assess hypoxia in bladder cancer. The objectives of the present study were to compare platforms for generating signature scores, identify cut­off values for prospective studies, assess intra­tumour heterogeneity and confirm hypoxia relevance. Briefly, RNA was extracted from prospectively collected diagnostic biopsies of muscle invasive bladder cancer (51 patients), and gene expression was measured using customised Taqman Low Density Array (TLDA) cards, NanoString and Clariom S arrays. Cross­platform transferability of the gene signature was assessed using regression and concordance analysis. The cut­off values were the cohort median expression values. Intra­ and inter­tumour variability were determined in a retrospective patient cohort (n=51) with multiple blocks (2­18) from the same tumour. To demonstrate relevance, bladder cancer cell lines were exposed to hypoxia (0.1% oxygen, 24 h), and extracted RNA was run on custom TLDA cards. Hypoxia scores (HS) values showed good agreement between platforms: Clariom S vs. TLDA (r=0.72, P<0.0001; concordance 73%); Clariom S vs. NanoString (r=0.84, P<0.0001; 78%); TLDA vs. NanoString (r=0.80, P<0.0001; 78%). Cut­off values were 0.047 (TLDA), 7.328 (NanoString) and 6.667 (Clariom S). Intra­tumour heterogeneity in gene expression and HS (coefficient of variation 3.9%) was less than inter­tumour (7.9%) variability. HS values were higher in bladder cancer cells exposed to hypoxia compared with normoxia (P<0.02). In conclusion, the present study revealed that application of the 24­gene bladder cancer hypoxia signature was platform agnostic, cut­off values determined prospectively can be used in a clinical trial, intra­tumour heterogeneity was low and the signature was sensitive to changes in oxygen levels in vitro.


Assuntos
Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Hipóxia/genética , Oxigênio , Estudos Prospectivos , RNA , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
17.
Aust Dent J ; 67(4): 328-339, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35718919

RESUMO

BACKGROUND: This population-based cohort study investigated dental procedures in the hospital setting in Western Australian children with or without intellectual disability (ID) and/or autism spectrum disorder (ASD) aged up to 18 years. Considering previously reported disparities in dental disease between Indigenous and non-Indigenous Australian children, this study also investigated the effect of Indigenous status on dental procedures. METHODS: Data on Western Australian live births from 1983 to 2010 from the Midwives Notification System were linked to the Intellectual Disability Exploring Answers database and the Hospital Morbidity Data collection. Primary admissions for relevant dental diagnoses were identified, and treatment procedures for dental hospitalization were investigated. Descriptive statistics and Pearson's chi-squared test of independence were used for analysis. RESULTS: Overall, 76 065 episodes of dental hospitalization were recorded. Amongst children with ID and/or ASD, Indigenous children experienced more extractions and fewer restorations (68.7% and 16.2%) compared to non-Indigenous children (51.5% and 25.9%). After 6 years, extraction occurred less often in children with ID and/or ASD than in those without, where most surgical dental extractions were in the age group of 13-18 years. CONCLUSIONS: This study indicates a need for further improvements in access to dental services and the quality of care provided in hospitals for children with ID/ASD. There is also concern that more vulnerable Indigenous and all disadvantaged children are receiving an inadequate level of dental services resulting in more emergency dental hospitalization and invasive treatment.


Assuntos
Transtorno do Espectro Autista , Deficiência Intelectual , Criança , Humanos , Idoso , Adolescente , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologia , Estudos de Coortes , Austrália , Hospitais , Odontologia
18.
Pituitary ; 25(5): 709-712, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35666391

RESUMO

Management of Cushing's disease is informed by dedicated imaging of the sella and parasellar regions. Although magnetic resonance imaging (MRI) remains the investigation of choice, a significant proportion (30-50%) of corticotroph tumours are so small as to render MRI indeterminate or negative when using standard clinical sequences. In this context, alternative MR protocols [e.g. 3D gradient (recalled) echo, with acquisition of volumetric data] may allow detection of tumors that have not been previously visualized. The use of hybrid molecular imaging (e.g. 11C-methionine positron emission tomography coregistered with volumetric MRI) has also been proposed as an additional modality for localizing microadenomas.


Assuntos
Adenoma , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Humanos , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico , Adenoma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Metionina
19.
Pathobiology ; : 1-13, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705026

RESUMO

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. METHODS: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. RESULTS: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. CONCLUSION: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

20.
Urol Oncol ; 40(8): 382.e1-382.e6, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35750559

RESUMO

PURPOSE: The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis. MATERIALS AND METHODS: All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant. RESULTS: HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09). CONCLUSIONS: Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy.


Assuntos
Cistoscopia , Neoplasias da Bexiga Urinária , Ácido Aminolevulínico/efeitos adversos , Ácido Aminolevulínico/análogos & derivados , Cistectomia/métodos , Cistoscopia/métodos , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
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