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1.
Curr Opin Ophthalmol ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38920096

RESUMO

PURPOSE OF REVIEW: To discuss available premium intraocular lenses (IOLs), patient selection, and important considerations for each premium IOL. RECENT FINDINGS: We review important topics and considerations for premium IOL selection: specifically, toric, extended depth of focus (EDOF), multifocal/trifocal, light adjustable lenses (LALs), and small aperture IOLs. Toric lenses are an excellent option for patients with astigmatism. However, to achieve optimal patient satisfaction, it is critical to account for the ATR astigmatism contribution from the posterior cornea and high angle alphas. Additionally, examining the ocular surface prior to placement of EDOF/multifocal IOLs is important, yet the significance of HOAs on outcomes after implantation still must be elucidated more. Finally, recent studies reveal that the small aperture lens is a good alternative for those with corneal irregularities, and second generation LALs are a great option to achieve target refractions in those with less predictable refractive outcomes, such as in Fuchs' dystrophy or in eyes with previous refractive surgery.

2.
J Exp Psychol Gen ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512178

RESUMO

Many organizations want to achieve diversity, yet who "counts" as contributing to diversity is malleable. Across four experiments, we explore how contextual influences shape perceptions of diversity, including what happens when information at different contextual levels conflicts. In Study 1 (N = 160) and Study 2 (N = 69, preregistered), we find that when participants believe White women, White men, and Black men to be overrepresented in a profession at the national level, individuals with those identities are rated as contributing less to the diversity of a group of workers within that profession. In Study 3 (N = 164), participants were asked to make diversity judgments within the same profession (American elementary school teachers), but the composition of the target group under evaluation was either White female-dominated (aligned with the profession) or White male-dominated (diverged from the profession). Presenting the group as White male-dominated (compared to White female-dominated) increased perceptions of White women's contributions to diversity and decreased perceptions of White men's, and men of color's, contributions to diversity. In Study 4 (N = 216, preregistered), we attempted to call participants' attention to representation at a single level only (i.e., national vs. target group), when representation information conflicted across levels. However, perceived contributions to diversity did not shift based on experimental conditions. It appears that Americans' judgments of who increases a group's diversity can be affected by representation at multiple levels, although it may be difficult for perceivers to prioritize one contextual level only when such information conflicts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

4.
Semin Oncol Nurs ; 40(1): 151577, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38245388

RESUMO

OBJECTIVES: Purposes were to identify subgroups of adult oncology patients (n = 1342) with distinct joint profiles of worst pain and cognitive function (CF) and evaluate for differences in demographic and clinical characteristics, as well as the severity of three distinct types of stress, resilience, and coping. DATA SOURCES: Measures of pain and CF were evaluated six times over two cycles of chemotherapy. The other measures of demographic and clinical characteristics, stress, resilience, and coping were completed at enrollment (ie, prior to the second or third cycle of chemotherapy). RESULTS: Using latent profile analysis, four distinct profiles were identified (ie, no pain + moderate CF [27.6%], moderate pain + high CF [22.4%] moderate pain and moderate CF [32.4%, both moderate], severe pain and low CF [17.5%, both severe]). Both moderate and both severe classes reported higher global, cancer-specific, and cumulative life stress, lower levels of resilience, and greater use of disengagement coping strategies. The Both severe class had higher occurrence rates for a number of adverse childhood experiences (ie, family violence in childhood, physical abuse at <16 years, forced sex at <16 years). Risk factors associated with membership in the two worst profiles included: being female, having a lower annual income, having a higher comorbidity burden, and having a poorer functional status. CONCLUSION: Findings suggest that 72.4% of the patients reported pain scores in the moderate to severe range and 77.6% reported low to moderate levels of CF. Clinicians need to assess for both symptoms and various types of stress on a routine basis.


Assuntos
Neoplasias , Dor , Adulto , Humanos , Feminino , Masculino , Estudos Longitudinais , Dor/tratamento farmacológico , Neoplasias/diagnóstico , Comorbidade , Cognição
5.
Neurorehabil Neural Repair ; 38(2): 109-121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38156644

RESUMO

BACKGROUND: Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus. OBJECTIVE: Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke. METHODS: Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS-TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation. RESULTS: Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability. CONCLUSIONS: Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery.


Assuntos
Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Cerebelo , Imagem de Tensor de Difusão , Potencial Evocado Motor/fisiologia , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Extremidade Superior , Ensaios Clínicos Fase I como Assunto
6.
Nat Med ; 29(9): 2366-2374, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37580534

RESUMO

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .


Assuntos
Estimulação Encefálica Profunda , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estimulação Encefálica Profunda/efeitos adversos , Resultado do Tratamento , Acidente Vascular Cerebral/terapia , Cerebelo , Recuperação de Função Fisiológica
7.
Pers Soc Psychol Bull ; : 1461672231190264, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559509

RESUMO

We examined how the number of groups in a categorization task influences how White Americans categorize ambiguous faces. We investigated the strength of identity-driven ingroup overexclusion-wherein highly identified perceivers overexclude ambiguous members from the ingroup-proposing that, compared with dichotomous tasks (with only the ingroup and one outgroup), tasks with more outgroups attenuate identity-driven ingroup overexclusion (a dilution effect). Fourteen studies (n = 4,001) measured White Americans' racial identification and their categorizations of ambiguous faces and manipulated the categorization task to have two groups, three groups, or an unspecified number of groups (open-ended). In all three conditions, participants overexcluded faces from the White category on average. There was limited support for the dilution effect: identity-driven ingroup overexclusion was absent in the three-group task and only weakly supported in the open-ended task. The presence of multiple outgroups may dampen the impact of racial identity on race perceptions among White Americans.

8.
SAGE Open Med ; 11: 20503121231162410, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993781

RESUMO

Objectives: Hip fractures represent a prevalent geriatric cause of morbidity and mortality. The presence of multiple comorbidities requiring the use of an anticoagulant or antiplatelet medication adds complexity to management and influences outcomes. International guidelines suggest expedited surgery within 48 h; however, anticoagulant and antiplatelet medications commonly cause delays. Research exploring health outcomes in this group is unclear. Therefore, we aimed to determine the impact of anticoagulant and antiplatelet medications on operative delay and overall complications in hip fracture patients. Methods: A retrospective cohort study of hip fractures was performed at a tertiary hospital over a 3-year period from 1st January 2018 to 31st December 2020. Data collected included demographics, time to surgery, length of stay, postoperative blood transfusion, venous thromboembolism, acute coronary syndrome, stroke, infections in hospital and 120-day mortality. Patients were categorised based on the use of direct oral anticoagulants, warfarin and antiplatelet medications. Results: In total, 474 patients were included and 43.5% were on an anticoagulant or antiplatelet medication. Patients on these medications had more than twice the rate of operative delay (41.7% versus 17.2%, p < 0.001) with the greatest in the direct oral anticoagulant group (92.7% delay). After controlling for age and gender, this was still significant for direct oral anticoagulant (p < 0.001) and antiplatelet group patients (p = 0.02). These patients also had a 20% increased overall complication rate (p < 0.001). On subgroup logistic regression, the increased complication rate was noted in the direct oral anticoagulant group (p = 0.006) and the antiplatelet group (p < 0.001) but not in the warfarin group (p = 0.25). Time to surgery beyond 48 h was associated with a double increase in the odds of a postoperative complication (p = 0.005). Conclusion: There is a significantly greater delay to surgery in hip fracture patients on anticoagulant or antiplatelet medications as well as a higher incidence of complications. Guidelines to expedite early safe surgery in this high-risk patient group are required.

9.
J Pers Soc Psychol ; 125(4): 827-851, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36996168

RESUMO

People often self-identify as allies to the lesbian, gay, bisexual, and transgender (LGBT) community. This research examined on what basis LGBT individuals perceive others to be allies and documents the consequences of perceived allyship. Studies 1a (n = 40) and 1b (n = 69) collected open-ended descriptions of allyship provided by LGBT participants. Coding of the responses suggested multiple components to being an ally: (a) being nonprejudiced toward the group, (b) taking action against discrimination and inequality, and (c) having humility about one's perspective in discussions about LGBT issues. In Studies 2a (n = 161) and 2b (n = 319, with nationally representative characteristics), an allyship scale was developed and validated for general and specific relational contexts, respectively. Study 2b also showed that LGBT individuals' perceptions of close others' allyship were positively associated with their own well-being and relationship quality with the close other. Study 3, an experiment, demonstrated that nonprejudice and action had an interactive effect on perceived allyship, such that action increased perceived allyship more when prejudice was low (vs. high). Study 4 was a weekly experience study of LGBT participants and an outgroup roommate. Perceiving one's roommate to be a good ally predicted higher self-esteem, greater subjective well-being, and better relationship quality with the roommate, both between and within participants. Furthermore, perceived allyship in 1 week was associated with increases in LGBT individuals' mental health and relationship quality with the roommate the following week. This research advances knowledge about what allyship means to LGBT individuals and identifies intra- and interpersonal benefits of allyship. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Homossexualidade Feminina , Minorias Sexuais e de Gênero , Pessoas Transgênero , Feminino , Humanos , Bissexualidade/psicologia , Homossexualidade Feminina/psicologia , Comportamento Sexual
10.
Oper Neurosurg (Hagerstown) ; 24(6): 641-650, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36827201

RESUMO

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is used to treat essential tremor and tremor-dominant Parkinson disease. Feedback is collected throughout the procedure to verify the location of the target and completeness of response; however, variability in clinical judgments may underestimate or overestimate treatment response. OBJECTIVE: To objectively quantify joint motion after each sonication using accelerometers secured to the contralateral upper extremity in an effort to optimize MRgFUS treatment. METHODS: Before the procedure, 3 accelerometers were secured to the patient's arm, forearm, and index finger. Throughout the procedure, tremor motion was regularly recorded during postural and kinetic tremor testing and individual joint angle measures were modeled. The joint angle from each accelerometer was compared with baseline measurements to assess changes in angles. Subsequent adjustments to the target location and sonication energy were made at the discretion of the neurosurgeon and neuroradiologist. RESULTS: Intraoperative accelerometer measurements of hand tremor from 18 patients provided quantified data regarding joint angle reduction: 87.3%, 94.2%, and 86.7% for signature writing, spiral drawing, and line drawing tests, respectively. Target adjustment based on accelerometer monitoring of the angle at each joint added substantial value toward achieving optimal tremor reduction. CONCLUSION: Real-time accelerometer recordings collected during MRgFUS thalamotomy offered objective quantification of changes in joint angle after each sonication, and these findings were consistent with clinical judgments of tremor response. These results suggest that this technique could be used for fine adjustment of the location of sonication energy and number of sonications to consistently achieve optimal tremor reduction.


Assuntos
Imageamento por Ressonância Magnética , Tremor , Humanos , Tremor/diagnóstico por imagem , Tremor/cirurgia , Estudos de Viabilidade , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Acelerometria
11.
J Soc Psychol ; 163(4): 459-479, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34843426

RESUMO

Two studies examine Multiracial Asian-White, Black-White, Latinx-White, and Native American-White people's experiences of rejection (Study 1) and acceptance (Study 2) from potential racial ingroups, and associations with life satisfaction. In Study 1, Multiracial participants reported comparable levels of rejection from their monoracial minoritized ingroups and White ingroup, but significantly less rejection from their Multiracial ingroup. In Study 2, participants reported feeling slightly less accepted from monoracial minoritized ingroups than from the White ingroup. Across both studies, greater rejection, and less acceptance, from the White ingroup was related to lower life satisfaction. Notably, this effect was strongest among Native American-White Multiracial people relative to other Multiracial groups in our sample. Findings highlight how Multiracial people's multiple potential ingroups relate to their social rejection and acceptance experiences, and that rejection and acceptance from higher status potential ingroups (i.e., White people) may play a role in subjective well-being disparities for some Multiracial groups.


Assuntos
Satisfação Pessoal , Grupos Raciais , Humanos , Brancos
12.
Br J Psychol ; 114 Suppl 1: 188-211, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35941787

RESUMO

The other-race effect (ORE) is a recognition memory advantage afforded to one's racial ingroup versus outgroup. The motivational relevance of the ingroup-because of relationships, belonging and self-esteem-is central to many theoretical explanations for the ORE. However, to date, the motivational relevance of outgroups has received considerably less attention in the ORE literature. Across six experiments, Black, White, Asian and Latinx American participants consistently demonstrated better recognition memory for the faces of relatively higher-status racial/ethnic group members than those of lower-status groups. This higher-status recognition advantage even appeared to override the ORE, such that participants better recognized members of higher-status outgroups-but not an outgroup of equivalent status-compared to members of their own ingroup. However, across a variety of self-reported perceived status measures, status differences between the high- and low-status groups generally did not moderate the documented recognition advantage. These findings provide initial evidence for the potential role of group status in the ORE and in recognition memory more broadly, but future work is needed to rule out alternative explanations.


Assuntos
Face , Grupos Raciais , Humanos , Reconhecimento Psicológico , Atenção , Autoimagem
13.
IEEE Trans Vis Comput Graph ; 29(1): 548-558, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36166541

RESUMO

Spatial statistical analysis of multivariate volumetric data can be challenging due to scale, complexity, and occlusion. Advances in topological segmentation, feature extraction, and statistical summarization have helped overcome the challenges. This work introduces a new spatial statistical decomposition method based on level sets, connected components, and a novel variation of the restricted centroidal Voronoi tessellation that is better suited for spatial statistical decomposition and parallel efficiency. The resulting data structures organize features into a coherent nested hierarchy to support flexible and efficient out-of-core region-of-interest extraction. Next, we provide an efficient parallel implementation. Finally, an interactive visualization system based on this approach is designed and then applied to turbulent combustion data. The combined approach enables an interactive spatial statistical analysis workflow for large-scale data with a top-down approach through multiple-levels-of-detail that links phase space statistics with spatial features.

14.
Asia Pac J Ophthalmol (Phila) ; 11(4): 314-327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36041146

RESUMO

Retinal degeneration (RD) is a significant cause of incurable blindness worldwide. Photoreceptors and retinal pigmented epithelium are irreversibly damaged in advanced RD. Functional replacement of photoreceptors and/or retinal pigmented epithelium cells is a promising approach to restoring vision. This paper reviews the current status and explores future prospects of the transplantation therapy provided by pluripotent stem cell-derived retinal organoids (ROs). This review summarizes the status of rodent RD disease models and discusses RO culture and analytical tools to evaluate RO quality and function. Finally, we review and discuss the studies in which RO-derived cells or sheets were transplanted. In conclusion, methods to derive ROs from pluripotent stem cells have significantly improved and become more efficient in recent years. Meanwhile, more novel technologies are applied to characterize and validate RO quality. However, opportunity remains to optimize tissue differentiation protocols and achieve better RO reproducibility. In order to screen high-quality ROs for downstream applications, approaches such as noninvasive and label-free imaging and electrophysiological functional testing are promising and worth further investigation. Lastly, transplanted RO-derived tissues have allowed improvements in visual function in several RD models, showing promises for clinical applications in the future.


Assuntos
Organoides , Degeneração Retiniana , Humanos , Espécies Reativas de Oxigênio , Reprodutibilidade dos Testes , Retina , Degeneração Retiniana/terapia
16.
Free Radic Biol Med ; 178: 125-133, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34871763

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, with poor prognosis and no cure. Substantial evidence implicates inflammation and associated oxidative stress as a potential mechanism for ALS, especially in patients carrying the SOD1 mutation and, therefore, lacking anti-oxidant defense. The brain is particularly vulnerable to oxidation due to the abundance of polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), which can give rise to several oxidized metabolites. Accumulation of a DHA peroxidation product, CarboxyEthylPyrrole (CEP) is dependent on activated inflammatory cells and myeloperoxidase (MPO), and thus marks areas of inflammation-associated oxidative stress. At the same time, generation of an alternative inactive DHA peroxidation product, ethylpyrrole, does not require cell activation and MPO activity. While absent in normal brain tissues, CEP is accumulated in the central nervous system (CNS) of ALS patients, reaching particularly high levels in individuals carrying a SOD1 mutation. ALS brains are characterized by high levels of MPO and lowered anti-oxidant activity (due to the SOD1 mutation), thereby aiding CEP generation and accumulation. Due to DHA oxidation within the membranes, CEP marks cells with the highest oxidative damage. In all ALS cases CEP is present in nearly all astrocytes and microglia, however, only in individuals carrying a SOD1 mutation CEP marks >90% of neurons, thereby emphasizing an importance of CEP accumulation as a potential hallmark of oxidative damage in neurodegenerative diseases.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Esclerose Lateral Amiotrófica/genética , Animais , Modelos Animais de Doenças , Humanos , Inflamação/genética , Camundongos , Camundongos Transgênicos , Mutação , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética
17.
Mult Scler ; 28(2): 198-205, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34014144

RESUMO

BACKGROUND: Detecting cortical demyelination using magnetic resonance imaging (MRI) in multiple sclerosis (MS) remains a challenge. Magnetization transfer ratio (MTR), T1-weighted/T2-weighted ratio (T1T2R), and T2-weighted (T2w) signal are sensitive to cortical demyelination, but their accuracy is unknown. OBJECTIVES: To quantify the sensitivity, specificity, and accuracy of postmortem T1T2R, MTR, and T2w in detecting cortical demyelination. METHODS: In situ postmortem MRIs from 9 patients were used to measure T1T2R, MTR, and T2w along the midline of cortical gray matter and classified as normal or abnormal. MRIs were co-registered and compared to hemispheric myelin staining. The sensitivity, specificity, and accuracy of T1T2R, MTR, and T2w in detecting cortical demyelination were measured. RESULTS: The mean age (standard deviation) at death was 64.7 (+/-13.7) years with a disease duration of 23.8 (+/-10.5) years. The sensitivity was 78% for MTR, 75% for T1T2R, and 63% for T2w. The specificity was 46% (T2w), 13% (T1T2R), and 29% (MTR). The accuracy was 71% (T2w), 39% (MTR), and 42% (T1T2R). There were no significant differences between different MRI measures in cortical demyelination or intracortical/subpial lesion detection. CONCLUSIONS: Although somewhat sensitive, the modest specificity of conventional MRI modalities for cortical demyelination indicates that they are influenced by cortical changes other than demyelination. Improved acquisition and post-processing are needed to reliably measure cortical lesion load.


Assuntos
Imageamento por Ressonância Magnética , Esclerose Múltipla , Idoso , Autopsia , Encéfalo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Bainha de Mielina/patologia
18.
Dig Dis Sci ; 67(5): 1858-1868, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33973084

RESUMO

BACKGROUND: Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS: Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS: Single-center retrospective cohort study of SOT recipients. RESULTS: 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION: SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.


Assuntos
Adenoma , Pólipos Adenomatosos , Neoplasias do Colo , Pólipos do Colo , Neoplasias Colorretais , Transplante de Órgãos , Adenoma/diagnóstico , Pólipos Adenomatosos/complicações , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/etiologia , Pólipos do Colo/diagnóstico , Colonoscopia/efeitos adversos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Humanos , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
19.
Am J Physiol Gastrointest Liver Physiol ; 322(1): G154-G168, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34816756

RESUMO

Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to 2 yr to determine which patients will wean from PN. Here, we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Stool and sera were collected from healthy controls and from patients with SBS (n = 52) with ileostomy, jejunostomy, ileocolonic, and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling, and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS and serum amino acid analyses. Patients with SBS exhibited altered gut microbiota with reduced gut microbial diversity compared with healthy controls. We observed differences in the microbiomes of patients with SBS with ileostomy versus jejunostomy, jejunocolonic versus ileocolonic anastomoses, and PN dependence compared with those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in patients with SBS, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who were weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic aicd. Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select patients with SBS, promoting the ability to wean from PN. Proadaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.NEW & NOTEWORTHY Loss of intestinal surface area causes short bowel syndrome, intestinal failure, and parenteral nutrition dependence. We analyzed the gut microbiota and bile acid metabolome of a large cohort of short bowel syndrome adult patients with different postsurgical anatomies. We report a novel analysis of the microbiome of patients with ileostomy and jejunostomy. Enrichment of specific microbial and bile acid species may be associated with the ability to wean from parenteral nutrition.


Assuntos
Ácidos e Sais Biliares/metabolismo , Fezes/microbiologia , RNA Ribossômico 16S/metabolismo , Síndrome do Intestino Curto/metabolismo , Adaptação Fisiológica/fisiologia , Cromatografia Líquida , Microbioma Gastrointestinal/fisiologia , Humanos , Intestino Delgado/metabolismo , Metaboloma/fisiologia , Microbiota/fisiologia
20.
Front Cell Neurosci ; 15: 796903, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955757

RESUMO

Pluripotent stem cell-derived organoid technologies have opened avenues to preclinical basic science research, drug discovery, and transplantation therapy in organ systems. Stem cell-derived organoids follow a time course similar to species-specific organ gestation in vivo. However, heterogeneous tissue yields, and subjective tissue selection reduce the repeatability of organoid-based scientific experiments and clinical studies. To improve the quality control of organoids, we introduced a live imaging technique based on two-photon microscopy to non-invasively monitor and characterize retinal organoids' (RtOgs') long-term development. Fluorescence lifetime imaging microscopy (FLIM) was used to monitor the metabolic trajectory, and hyperspectral imaging was applied to characterize structural and molecular changes. We further validated the live imaging experimental results with endpoint biological tests, including quantitative polymerase chain reaction (qPCR), single-cell RNA sequencing, and immunohistochemistry. With FLIM results, we analyzed the free/bound nicotinamide adenine dinucleotide (f/b NADH) ratio of the imaged regions and found that there was a metabolic shift from glycolysis to oxidative phosphorylation. This shift occurred between the second and third months of differentiation. The total metabolic activity shifted slightly back toward glycolysis between the third and fourth months and stayed relatively stable between the fourth and sixth months. Consistency in organoid development among cell lines and production lots was examined. Molecular analysis showed that retinal progenitor genes were expressed in all groups between days 51 and 159. Photoreceptor gene expression emerged around the second month of differentiation, which corresponded to the shift in the f/b NADH ratio. RtOgs between 3 and 6 months of differentiation exhibited photoreceptor gene expression levels that were between the native human fetal and adult retina gene expression levels. The occurrence of cone opsin expression (OPN1 SW and OPN1 LW) indicated the maturation of photoreceptors in the fourth month of differentiation, which was consistent with the stabilized level of f/b NADH ratio starting from 4 months. Endpoint single-cell RNA and immunohistology data showed that the cellular compositions and lamination of RtOgs at different developmental stages followed those in vivo.

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