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1.
bioRxiv ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38496613

RESUMO

Targeted, genome-scale gene perturbation screens using Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) and activation (CRISPRa) have revolutionized eukaryotic genetics, advancing medical, industrial, and basic research. Although CRISPRi knockdowns have been broadly applied in bacteria, options for genome-scale overexpression face key limitations. Here, we develop a facile approach for genome-scale gene overexpression in bacteria we call, "CRISPRtOE" (CRISPR transposition and OverExpression). We create a platform for comprehensive gene targeting using CRISPR-associated transposition (CAST) and show that transposition occurs at a higher frequency in non-transcribed DNA. We then demonstrate that CRISPRtOE can upregulate gene expression in Proteobacteria with medical and industrial relevance by integrating synthetic promoters of varying strength upstream of target genes. Finally, we employ CRISPRtOE screening at the genome-scale in Escherichia coli, recovering known antibiotic targets and genes with unexplored roles in antibiotic function. We envision that CRISPRtOE will be a valuable overexpression tool for antibiotic mode of action, industrial strain optimization, and gene function discovery in bacteria.

2.
Harm Reduct J ; 21(1): 67, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515184

RESUMO

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is drug of high prevalence in Aotearoa New Zealand and is the primary drug analysed by legal drug checking services. We aimed to address the gap in literature pertaining to MDMA-related harm reduction behaviour and harm experiences within the country. METHODS: An online survey was used to assess the harm reduction behaviours (e.g., limiting consumption, planning use, seeking information) of people who use MDMA, in addition to their use of reagent testing and the major national drug checking and harm reduction service, KnowYourStuffNZ. RESULTS: In total, 915 people completed the survey (60.7% females, aged 18-65, median = 24, IQR = 20-28). Frequency of various MDMA-related harm reduction behaviours differed, although these were carried out relatively frequently by most participants. Those who reported experiencing harm (physical, psychological, spiritual, social) from MDMA, or another drug presumed to be MDMA, reported less frequent harm reduction behaviours than non-harmed consumers. Reagent testing of MDMA had been conducted by 42.3% of the sample. Approximately 27% of the sample had used KnowYourStuffNZ services. Of KnowYourStuffNZ clients, 95.9% reported learning about harm reduction, and 53.3% reported changing their behaviour because of the service. Reasons for not using the KnowYourStuffNZ service were primarily lack of availability in local area (32.8%) or at relevant events (51.8%), and lack of concern with substance quality (29.8%). MDMA harm was reported by 14.4% of the sample, whilst reported harm was more common from consumption of presumably non-MDMA substances, self-reported as being mistaken for MDMA. Harm was primarily physical or psychological. Potential MDMA dependence was apparent in 6.9% of the sample. CONCLUSIONS: The findings highlight potential targets for harm reduction education and interventions and emphasize the need for greater availability of readily accessible drug checking services in Aotearoa New Zealand.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Transtornos Relacionados ao Uso de Substâncias , Feminino , Humanos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/análise , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Redução do Dano , Nova Zelândia/epidemiologia , Inquéritos e Questionários
3.
iScience ; 27(3): 109266, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439980

RESUMO

The basal forebrain (BF) is critical for the motivational recruitment of attention in response to reward-related cues. This finding is consistent with a role for the BF in encoding and transmitting motivational salience and readying prefrontal circuits for further attentional processing. We recorded local field potentials to determine connectivity between prelimbic cortex (PrL) and BF during the modulation of attention by reward-related cues. We find that theta and gamma power are robustly associated with behavior. Power in both bands is significantly lower during trials in which an incorrect behavioral response is made. We find strong coherence during responses that are significantly stronger when a correct response is made. We show that information flow is largely monodirectional from BF to and is strongest when correct responses are made. These experiments demonstrate that connectivity between BF and the PrL increases during periods of increased motivational recruitment of attentional resources.

4.
Front Oncol ; 14: 1276092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380370

RESUMO

Introduction: Resistance to drug therapies is associated with a large majority of cancer-related deaths. ATP-binding cassette (ABC) transporter-mediated drug efflux, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), glutathione (GSH), senescence, and vacuole-type ATPase (V-ATPase) all contribute to the resistance. We recently showed that extracellular ATP (eATP) induces and regulates EMT, CSC formation, and ABC transporters in human cancer cells and tumors. eATP also consistently upregulates Stanniocalcin-1 (STC1), a gene that significantly contributes to EMT, CSC formation, and tumor growth. We also found that eATP enhances drug resistance in cancer cells through eATP internalization mediated by macropinocytosis, leading to an elevation of intracellular ATP (iATP) levels, induction of EMT, and CSC formation. However, these factors have never been systematically investigated in the context of eATP-induced drug resistance. Methods: In this study, we hypothesized that eATP increases drug resistance via inducing ABC efflux, EMT, CSCs, STC1, and their accompanied processes such as GSH reducing activity, senescence, and V-ATPase. RNA sequencing, metabolomics, gene knockdown and knockout, and functional assays were performed to investigate these pathways and processes. Results and discussion: Our study results showed that, in multiple human cancer lines, eATP induced genes involved in drug resistance, elevated ABC transporters' efflux activity of anticancer drugs; generated transcriptomic and metabolic profiles representing a drug resistant state; upregulated activities of GSH, senescence, and V-ATPase to promote drug resistance. Collectively, these newly found players shed light on the mechanisms of eATP-induced as well as STC1- and V-ATPase-mediated drug resistance and offer potential novel targets for combating drug resistance in cancers.

5.
Drug Alcohol Rev ; 43(1): 36-44, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36917507

RESUMO

INTRODUCTION: TikTok has quickly gained popularity through its platforming of large amounts of short video content. Given its widespread popularity, unrestricted access and poor content monitoring may allow 3,4-methylenedioxymethamphetamine (MDMA)-related content to influence perception of MDMA use. We aimed to investigate how MDMA-related videos are portrayed on TikTok and explore MDMA-related harm reduction content. METHODS: MDMA-related hashtags and sounds were utilised to collect data from TikTok (n = 498). Video views, likes, comments and shares were recorded and quantified, and videos were coded for depiction/sentiment towards MDMA and thematic content. RESULTS: The total sample view count was 82,413,781. Videos had a median view count of 28,900 (SD = ±561,645), median like count of 2269 (SD = ±102,904), median comment count of 52 (SD = ±755), and median share count of 34 (SD = ±3292). Most videos depicted MDMA neutrally (40.6%), while 34.9% were positive. MDMA intoxication was presumed in 40.2% of videos. The analysis produced seven themes, of which humour was the most common (80.5%). Harm reduction content was present in nine videos, viewed 999,700 times, and consisted of mixed subject matter. DISCUSSION AND CONCLUSIONS: Similar themes and issues surrounding drug-related content on TikTok are relevant to MDMA, and intoxication was present in a significant portion of the sample. Better monitoring or regulation of content could potentially offset harm that may arise from consumption of such content. Promotion of harm reduction content could also be trialled to minimise harm.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Mídias Sociais , Humanos , Emoções , Redução do Dano
6.
Neuroimage ; 285: 120483, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38048921

RESUMO

The integration of information from different sensory modalities is a fundamental process that enhances perception and performance in real and virtual environments (VR). Understanding these mechanisms, especially during learning tasks that exploit novel multisensory cue combinations provides opportunities for the development of new rehabilitative interventions. This study aimed to investigate how functional brain changes support behavioural performance improvements during an audio-visual (AV) learning task. Twenty healthy participants underwent a 30 min daily VR training for four weeks. The task was an AV adaptation of a 'scanning training' paradigm that is commonly used in hemianopia rehabilitation. Functional magnetic resonance imaging (fMRI) and performance data were collected at baseline, after two and four weeks of training, and four weeks post-training. We show that behavioural performance, operationalised as mean reaction time reduction in VR, significantly improves. In separate tests in a controlled laboratory environment, we showed that the behavioural performance gains in the VR training environment transferred to a significant mean RT reduction for the trained AV voluntary task on a computer screen. Enhancements were observed in both the visual-only and AV conditions, with the latter demonstrating a faster response time supported by the presence of audio cues. The behavioural learning effect also transfers to two additional tasks that were tested: a visual search task and an involuntary visual task. Our fMRI results reveal an increase in functional activation (BOLD signal) in multisensory brain regions involved in early-stage AV processing: the thalamus, the caudal inferior parietal lobe and cerebellum. These functional changes were only observed for the trained, multisensory, task and not for unimodal visual stimulation. Functional activation changes in the thalamus were significantly correlated to behavioural performance improvements. This study demonstrates that incorporating spatial auditory cues to voluntary visual training in VR leads to augmented brain activation changes in multisensory integration, resulting in measurable performance gains across tasks. The findings highlight the potential of VR-based multisensory training as an effective method for enhancing cognitive function and as a potentially valuable tool in rehabilitative programmes.


Assuntos
Imageamento por Ressonância Magnética , Realidade Virtual , Humanos , Aprendizagem , Encéfalo/fisiologia , Percepção Visual , Cegueira , Percepção Auditiva
7.
mBio ; 15(2): e0205123, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38126769

RESUMO

The emergence of multidrug-resistant Gram-negative bacteria underscores the need to define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative pathogen, Acinetobacter baumannii, is considered an urgent threat due to its propensity to evade antibiotic treatments. Essential cellular processes are the target of existing antibiotics and a likely source of new vulnerabilities. Although A. baumannii essential genes have been identified by transposon sequencing, they have not been prioritized by sensitivity to knockdown or antibiotics. Here, we take a systems biology approach to comprehensively characterize A. baumannii essential genes using CRISPR interference (CRISPRi). We show that certain essential genes and pathways are acutely sensitive to knockdown, providing a set of vulnerable targets for future therapeutic investigation. Screening our CRISPRi library against last-resort antibiotics uncovered genes and pathways that modulate beta-lactam sensitivity, an unexpected link between NADH dehydrogenase activity and growth inhibition by polymyxins, and anticorrelated phenotypes that may explain synergy between polymyxins and rifamycins. Our study demonstrates the power of systematic genetic approaches to identify vulnerabilities in Gram-negative pathogens and uncovers antibiotic-essential gene interactions that better inform combination therapies.IMPORTANCEAcinetobacter baumannii is a hospital-acquired pathogen that is resistant to many common antibiotic treatments. To combat resistant A. baumannii infections, we need to identify promising therapeutic targets and effective antibiotic combinations. In this study, we comprehensively characterize the genes and pathways that are critical for A. baumannii viability. We show that genes involved in aerobic metabolism are central to A. baumannii physiology and may represent appealing drug targets. We also find antibiotic-gene interactions that may impact the efficacy of carbapenems, rifamycins, and polymyxins, providing a new window into how these antibiotics function in mono- and combination therapies. Our studies offer a useful approach for characterizing interactions between drugs and essential genes in pathogens to inform future therapies.


Assuntos
Acinetobacter baumannii , Rifamicinas , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Genes Essenciais , Polimixinas/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Rifamicinas/metabolismo , Rifamicinas/farmacologia , Testes de Sensibilidade Microbiana
8.
Environ Sci Technol ; 57(48): 19519-19531, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38000445

RESUMO

State inventories indicate that dairy operations account for nearly half of California's methane budget. Recent analyses suggest, however, that these emissions may be underestimated, complicating efforts to develop emission reduction strategies. Here, we report estimates of dairy methane emissions in the southern San Joaquin Valley (SJV) of California in June 2021 using airborne flux measurements. We find average dairy methane fluxes of 512 ± 178 mg m-2 h-1 from a region of 300+ dairies near Visalia, CA using a combination of eddy covariance and mass balance-based techniques, corresponding to 118 ± 41 kg dairy-1 h-1. These values estimated during our June campaign are 39 ± 48% larger than annual average estimates from the recently developed VISTA-CA inventory. We observed notable increases in emissions with temperature. Our estimates align well with inventory predictions when parametrizations for the temperature dependence of emissions are applied. Our measurements further demonstrate that the VISTA-CA emission inventory is considerably more accurate than the EPA GHG-I inventory in this region. Source apportionment analyses confirm that dairy operations produce the majority of methane emissions in the southern SJV (∼65%). Fugitive oil and gas (O&G) sources account for the remaining ∼35%. Our results support the accuracy of the process-based models used to develop dairy emission inventories and highlight the need for additional investigation of the meteorological dependence of these emissions.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Metano/análise , Meio Ambiente , Gás Natural/análise , California
9.
Front Psychol ; 14: 1175703, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868596

RESUMO

Our brain constantly combines multisensory information from our surrounding environment. Odors for instance are often perceived with visual cues; these sensations interact to form our own subjective experience. This integration process can have a profound impact on the resulting experience and can alter our subjective reality. Crossmodal correspondences are the consistent associations between stimulus features in different sensory modalities. These correspondences are presumed to be bidirectional in nature and have been shown to influence our perception in a variety of different sensory modalities. Vision is dominant in our multisensory perception and can influence how we perceive information in our other senses, including olfaction. We explored the effect that different odors have on human color perception by presenting olfactory stimuli while asking observers to adjust a color patch to be devoid of hue (neutral gray task). We found a shift in the perceived neutral gray point to be biased toward warmer colors. Four out of five of our odors also trend toward their expected crossmodal correspondences. For instance, when asking observers to perform the neutral gray task while presenting the smell of cherry, the perceptually achromatic stimulus was biased toward a red-brown. Using an achromatic adjustment task, we were able to demonstrate a small but systematic effect of the presence of odors on human color perception.

10.
mBio ; : e0148723, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37905909

RESUMO

Reduced genome bacteria are genetically simplified systems that facilitate biological study and industrial use. The free-living alphaproteobacterium Zymomonas mobilis has a naturally reduced genome containing fewer than 2,000 protein-coding genes. Despite its small genome, Z. mobilis thrives in diverse conditions including the presence or absence of atmospheric oxygen. However, insufficient characterization of essential and conditionally essential genes has limited broader adoption of Z. mobilis as a model alphaproteobacterium. Here, we use genome-scale CRISPRi-seq (clustered regularly interspaced short palindromic repeats interference sequencing) to systematically identify and characterize Z. mobilis genes that are conditionally essential for aerotolerant or anaerobic growth or are generally essential across both conditions. Comparative genomics revealed that the essentiality of most "generally essential" genes was shared between Z. mobilis and other Alphaproteobacteria, validating Z. mobilis as a reduced genome model. Among conditionally essential genes, we found that the DNA repair gene, recJ, was critical only for aerobic growth but reduced the mutation rate under both conditions. Further, we show that genes encoding the F1FO ATP synthase and Rhodobacter nitrogen fixation (Rnf) respiratory complex are required for the anaerobic growth of Z. mobilis. Combining CRISPRi partial knockdowns with metabolomics and membrane potential measurements, we determined that the ATP synthase generates membrane potential that is consumed by Rnf to power downstream processes. Rnf knockdown strains accumulated isoprenoid biosynthesis intermediates, suggesting a key role for Rnf in powering essential biosynthetic reactions. Our work establishes Z. mobilis as a streamlined model for alphaproteobacterial genetics, has broad implications in bacterial energy coupling, and informs Z. mobilis genome manipulation for optimized production of valuable isoprenoid-based bioproducts. IMPORTANCE The inherent complexity of biological systems is a major barrier to our understanding of cellular physiology. Bacteria with markedly fewer genes than their close relatives, or reduced genome bacteria, are promising biological models with less complexity. Reduced genome bacteria can also have superior properties for industrial use, provided the reduction does not overly restrict strain robustness. Naturally reduced genome bacteria, such as the alphaproteobacterium Zymomonas mobilis, have fewer genes but remain environmentally robust. In this study, we show that Z. mobilis is a simplified genetic model for Alphaproteobacteria, a class with important impacts on the environment, human health, and industry. We also identify genes that are only required in the absence of atmospheric oxygen, uncovering players that maintain and utilize the cellular energy state. Our findings have broad implications for the genetics of Alphaproteobacteria and industrial use of Z. mobilis to create biofuels and bioproducts.

11.
Dig Dis Sci ; 68(12): 4350-4359, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37796405

RESUMO

BACKGROUND: The economic impact of perianal fistulas in Crohn's disease (CD) has not been formally assessed in population-based studies in the biologic era. AIM: To compare direct health care costs in persons with and without perianal fistulas. METHODS: We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive "cases" were matched to up to 4 "controls" with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls. RESULTS: A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater). CONCLUSION: In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term.


Assuntos
Doença de Crohn , Fístula Retal , Adulto , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/terapia , Seguimentos , Resultado do Tratamento , Estudos Retrospectivos , Fístula Retal/diagnóstico , Fístula Retal/epidemiologia , Custos de Cuidados de Saúde
12.
Artigo em Inglês | MEDLINE | ID: mdl-37711680

RESUMO

CeO2 and CuO nanoparticles (NPs) are used as additives in petrodiesel to enhance engine performance leading to reduced diesel combustion emissions. Despite their benefits, the additive application poses human health concerns by releasing inhalable NPs into the ambient air. In this study, a bioinspired lung cell exposure system, Dosimetric Aerosol in Vitro Inhalation Device (DAVID), was employed for evaluating the toxicity of aerosolized CeO2 and CuO NPs with a short duration of exposure (≤10 min vs. hours in other systems) and without exerting toxicity from non-NP factors. Human epithelial A549 lung cells were cultured and maintained within DAVID at the air-liquid interface (ALI), onto which aerosolized NPs were deposited, and experiments in submerged cells were used for comparison. Exposure of the cells to the CeO2 NPs did not result in detectable IL-8 release, nor did it produce a significant reduction in cell viability based on lactate dehydrogenase (LDH) assay, with a marginal decrease (10%) at the dose of 388 µg/cm2 (273 cm2/cm2). In contrast, exposure to CuO NPs resulted in a concentration dependent reduction in LDH release based on LDH leakage, with 38% reduction in viability at the highest dose of 52 µg/cm2 (28.3 cm2/cm2). Cells exposed to CuO NPs resulted in a dose dependent cellular membrane toxicity and expressed IL-8 secretion at a global dose five times lower than cells exposed under submerged conditions. However, when comparing the ALI results at the local cellular dose of CuO NPs to the submerged results, the IL-8 secretion was similar. In this study, we demonstrated DAVID as a new exposure tool that helps evaluate aerosol toxicity in simulated lung environment. Our results also highlight the necessity in choosing the right assay endpoints for the given exposure scenario, e.g., LDH for ALI and Deep Blue for submerged conditions for cell viability.

13.
bioRxiv ; 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37577569

RESUMO

The emergence of multidrug-resistant Gram-negative bacteria underscores the need to define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative pathogen, Acinetobacter baumannii, is considered an urgent threat due to its propensity to evade antibiotic treatments. Essential cellular processes are the target of existing antibiotics and a likely source of new vulnerabilities. Although A. baumannii essential genes have been identified by transposon sequencing (Tn-seq), they have not been prioritized by sensitivity to knockdown or antibiotics. Here, we take a systems biology approach to comprehensively characterize A. baumannii essential genes using CRISPR interference (CRISPRi). We show that certain essential genes and pathways are acutely sensitive to knockdown, providing a set of vulnerable targets for future therapeutic investigation. Screening our CRISPRi library against last-resort antibiotics uncovered genes and pathways that modulate beta-lactam sensitivity, an unexpected link between NADH dehydrogenase activity and growth inhibition by polymyxins, and anticorrelated phenotypes that underpin synergy between polymyxins and rifamycins. Our study demonstrates the power of systematic genetic approaches to identify vulnerabilities in Gram-negative pathogens and uncovers antibiotic-essential gene interactions that better inform combination therapies.

15.
Sci Rep ; 13(1): 10590, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391587

RESUMO

During the olfactory perception process, our olfactory receptors are thought to recognize specific chemical features. These features may contribute towards explaining our crossmodal perception. The physicochemical features of odors can be extracted using an array of gas sensors, also known as an electronic nose. The present study investigates the role that the physicochemical features of olfactory stimuli play in explaining the nature and origin of olfactory crossmodal correspondences, which is a consistently overlooked aspect of prior work. Here, we answer the question of whether the physicochemical features of odors contribute towards explaining olfactory crossmodal correspondences and by how much. We found a similarity of 49% between the perceptual and the physicochemical spaces of our odors. All of our explored crossmodal correspondences namely, the angularity of shapes, smoothness of textures, perceived pleasantness, pitch, and colors have significant predictors for various physicochemical features, including aspects of intensity and odor quality. While it is generally recognized that olfactory perception is strongly shaped by context, experience, and learning, our findings show that a link, albeit small (6-23%), exists between olfactory crossmodal correspondences and their underlying physicochemical features.


Assuntos
Percepção Olfatória , Olfato , Nariz Eletrônico , Emoções , Aprendizagem
16.
Epileptic Disord ; 25(2): 237-243, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37002552

RESUMO

OBJECTIVE: We examined seizure control during spontaneous responsive neurostimulation (RNS) battery failure to investigate the persistent benefits of RNS in the absence of neurostimulation. We hypothesized that the loss of direct RNS does not immediately result in seizure worsening. METHODS: Patients with RNS battery failure between August 2019 and December 2020 at a single institution were studied. During periods of battery depletion, the RNS device does not store any electrocorticography records, so we used a telephone-based survey and chart review to assess seizure control during battery depletion. RESULTS: Eight of 10 eligible participants responded to the survey, with a mean duration of battery failure of 36 days (range: 10-219 days). During battery depletion, one patient reported decreased seizures and five reported no changes in seizure frequency. Only two patients reported increased seizure frequency. SIGNIFICANCE: The benefits of RNS treatment may outlast the immediate effects of direct neurostimulation, lending support to the notion of persistent neuroplasticity. Larger studies should confirm our preliminary findings.


Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Humanos , Epilepsia Resistente a Medicamentos/terapia , Convulsões/terapia , Eletrocorticografia
17.
Br J Radiol ; 96(1144): 20220663, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745009

RESUMO

OBJECTIVE: Pelvic lymph node metastasis (PLNM) at the time of radical prostatectomy (RP) portends an unfavorable prognosis in prostate cancer patients. Conventional and advanced imaging remains limited in its ability to detect PLNM. We sought to evaluate the combination of a genomic classifier Decipher with Prostate Imaging Reporting and Data System (PI-RADS) scores in improving the detection of PLNM. METHODS: A retrospective review was performed of patients whom underwent RP, Decipher analysis, and pre-operative prostate MRI. Categorical variables were compared using Pearson chi-squareχ2 tests. Quantitative variables were assessed with Wilcoxon rank-sum tests. Multivariable logistic regression was used to identify predictors of PLNM on final pathology. RESULTS: In total, 202 patients were included in the analysis, 23 of whom (11%) had PLNM. Patients with PLNM had higher median Decipher scores (0.73) than those without PLNM (0.61; p = 0.003). Patients with PLNM were more likely to demonstrate PI-RADS scores ≥ 4 (96%) than those without PLNM (74%; p = 0.012). Logistic regression demonstrated an interaction between Decipher score with PI-RADS score ≥4 (OR = 20.41; 95% CI, 2.10-198.74; p = 0.009) The combination demonstrated an area under the curve (AUC) of 0.73 (95% CI, 0.63-0.82; p < 0.001) for predicting PLNM. CONCLUSION: The combination of elevated Decipher genomic score (≥ 0.6) and clinically significant PI-RADS score (≥ 4) is associated with PLNM at the time of RP in a modern high-risk cohort of patients with PCaprostate cancer. ADVANCES IN KNOWLEDGE: Prostate MRI and genomic testing may help identify patients with adverse pathology.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Gradação de Tumores , Prostatectomia/métodos , Genômica , Estudos Retrospectivos
18.
Am Surg ; 89(7): 3174-3179, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36792996

RESUMO

OBJECTIVES: Pan scanning in trauma patients has become routine, resulting in increased identification of incidental findings (IF), findings unrelated to the reason for the scan. This has posed a conundrum of ensuring patients have appropriate follow-up for these findings. We sought to evaluate our compliance and follow-up for patients after implementation of an IF protocol at our level-I trauma center. METHODS: We performed a retrospective review from 9/2020 to 4/2021, to encompass before and after protocol implementation. Patients were separated into PRE and POST groups. Charts were reviewed evaluating several factors including three- and six-month follow-ups on IF. Data were analyzed comparing PRE and POST groups. RESULTS: A total of 1989 patients were identified, 31.22% (n = 621) with an IF. 612 patients were included in our study. Compared to PRE, POST showed a significant increase in PCP notification (35% vs 22%, P < .001) and patient notification (82% vs 65%, P < .001). As a result, patient follow-up regarding IF at six months was significantly higher in POST (44%) v. PRE (29%), (P < .001). There was no difference in follow-up based on insurance carrier. There was no difference in patient age for PRE (63 y) and POST (66 y) overall, (P = .089); nor in age of patients who followed up; 68.8 PRE vs 68.2 years POST (P = .819). CONCLUSION: Implementation of an IF protocol with patient and PCP notification was significantly improved in overall patient follow-up for category one and two IF. Utilizing the results of this study, the protocol will be further revised to improve patient follow-up.


Assuntos
Achados Incidentais , Centros de Traumatologia , Humanos , Seguimentos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Literatura de Revisão como Assunto
19.
J Urol ; : 101097JU0000000000003156, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630568

RESUMO

PURPOSE: Prostatic urethral lift with UroLift is a minimally invasive approach to treat symptomatic benign prostatic hypertrophy. This device causes artifacts on prostate magnetic resonance images. Our aim was to evaluate the impact of artifact on prostate magnetic resonance image quality. MATERIALS AND METHODS: This was a single-center retrospective review of patients with UroLift who subsequently had prostate magnetic resonance imaging. Two readers graded UroLift artifact on each pulse sequence using a 5-point scale (1-nondiagnostic; 5-no artifact). Prostate Imaging Quality scores were assigned for the whole data set. The volume of gland obscured by artifact was measured. Linear and logistic regression models were used to identify predictors of poor image quality. RESULTS: Thirty-seven patients were included. Poor image quality occurs more in the transition zone than the peripheral zone (15% vs 3%), at base/mid regions vs the apex (13%, 9%, and 5%, respectively) and on diffusion-weighted images vs T2-weighted and dynamic contrast-enhanced sequences (27%, 0.3%, 0%, respectively; P < .001). Suboptimal image quality (ie, Prostate Imaging Quality score <2) was found in 16%-24% of exams. The percentage of gland obscured by the UroLift artifact was higher on diffusion-weighted images and dynamic contrast-enhanced sequences than T2-weighted (32%, 9%, and 6%, respectively; P < .001). CONCLUSIONS: UroLift artifact negatively affects prostate magnetic resonance image quality with greater impact in the mid-basal transition zone, obscuring a third of the gland on diffusion-weighted images. Patients considering this procedure should be counseled on the impact of this device on image quality and its potential implications for any image-guided prostate cancer workup.

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