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1.
J Neurosci ; 43(31): 5693-5709, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37369587

RESUMO

The trial-unique nonmatching to location (TUNL) touchscreen task shows promise as a translational assay of working memory (WM) deficits in rodent models of autism, ADHD, and schizophrenia. However, the low-level neurocognitive processes that drive behavior in the TUNL task have not been fully elucidated. In particular, it is commonly assumed that the TUNL task predominantly measures spatial WM dependent on hippocampal pattern separation, but this proposition has not previously been tested. In this project, we tested this question using computational modeling of behavior from male and female mice performing the TUNL task (N = 163 across three datasets; 158,843 trials). Using this approach, we empirically tested whether TUNL behavior solely measured retrospective WM, or whether it was possible to deconstruct behavior into additional neurocognitive subprocesses. Overall, contrary to common assumptions, modeling analyses revealed that behavior on the TUNL task did not primarily reflect retrospective spatial WM. Instead, behavior was best explained as a mixture of response strategies, including both retrospective WM (remembering the spatial location of a previous stimulus) and prospective WM (remembering an anticipated future behavioral response) as well as animal-specific response biases. These results suggest that retrospective spatial WM is just one of a number of cognitive subprocesses that contribute to choice behavior on the TUNL task. We suggest that findings can be understood within a resource-rational framework, and use computational model simulations to propose several task-design principles that we predict will maximize spatial WM and minimize alternative behavioral strategies in the TUNL task.SIGNIFICANCE STATEMENT Touchscreen tasks represent a paradigm shift for assessment of cognition in nonhuman animals by automating large-scale behavioral data collection. Their main relevance, however, depends on the assumption of functional equivalence to cognitive domains in humans. The trial-unique, delayed nonmatching to location (TUNL) touchscreen task has revolutionized the study of rodent spatial working memory. However, its assumption of functional equivalence to human spatial working memory is untested. We leveraged previously untapped single-trial TUNL data to uncover a novel set of hierarchically ordered cognitive processes that underlie mouse behavior on this task. The strategies used demonstrate multiple cognitive approaches to a single behavioral outcome and the requirement for more precise task design and sophisticated data analysis in interpreting rodent spatial working memory.


Assuntos
Hipocampo , Memória de Curto Prazo , Humanos , Camundongos , Masculino , Feminino , Animais , Memória de Curto Prazo/fisiologia , Estudos Prospectivos , Estudos Retrospectivos , Hipocampo/fisiologia , Transtornos da Memória , Viés
2.
Phys Rev Lett ; 132(11): 116601, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38563950

RESUMO

Ultrathin bismuth exhibits rich physics including strong spin-orbit coupling, ferroelectricity, nontrivial topology, and light-induced structural dynamics. We use ab initio calculations to show that light can induce structural transitions to four transient phases in bismuth monolayers. These light-induced phases exhibit nontrivial topological character, which we illustrate using the recently introduced concept of spin bands and spin-resolved Wilson loops. Specifically, we find that the topology changes via the closing of the electron and spin band gaps during photoinduced structural phase transitions, leading to distinct edge states. Our study provides strategies to tailor electronic and spin topology via ultrafast control of photoexcited carriers and associated structural dynamics.

3.
Brain Behav Immun ; 116: 349-361, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38142918

RESUMO

Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model. Selenium was administered via drinking water (1.5 ppm) to pregnant dams from gestational day (GD) 9 to birth, and MIA was induced at GD17 using polyinosinic:polycytidylic acid (poly-I:C, 20 mg/kg via intraperitoneal injection). Foetal placenta and brain cytokine levels were assessed using a Luminex assay and brain elemental nutrients assessed using inductively coupled plasma- mass spectrometry. Adult offspring were behaviourally assessed using a reinforcement learning paradigm, the three-chamber sociability test and the open field test. MIA elevated placental IL-1ß and IL-17, and Se supplementation successfully prevented this elevation. MIA caused an increase in foetal brain calcium, which was prevented by Se supplement. MIA caused in offspring a female-specific reduction in sociability, which was recovered by Se, and a male-specific reduction in social memory, which was not recovered by Se. Exposure to poly-I:C or selenium, but not both, reduced performance in the reinforcement learning task. Computational modelling indicated that this was predominantly due to increased exploratory behaviour, rather than reduced rate of learning the location of the food reward. This study demonstrates that while Se may be beneficial in ameliorating sociability deficits caused by MIA, it may have negative effects in other behavioural domains. Caution in the use of Se supplementation during pregnancy is therefore warranted.


Assuntos
Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Selênio , Camundongos , Animais , Feminino , Gravidez , Masculino , Humanos , Comportamento Animal/fisiologia , Selênio/farmacologia , Placenta , Modelos Animais de Doenças , Poli I-C/farmacologia , Suplementos Nutricionais
4.
J Sleep Res ; : e14161, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308529

RESUMO

The detrimental effects of sleep loss on overall decision-making have been well described. Due to the complex nature of decisions, there remains a need for studies to identify specific mechanisms of decision-making vulnerable to sleep loss. Bayesian perspectives of decision-making posit judgement formation during decision-making occurs via a process of integrating knowledge gleaned from past experiences (priors) with new information from current observations (likelihoods). We investigated the effects of sleep loss on the ability to integrate multiple sources of information during decision-making by reporting results from two experiments: the first implementing both sleep restriction (SR) and total sleep deprivation (TSD) protocols, and the second implementing an SR protocol. In both experiments, participants were administered the Bayes Decisions Task on which optimal performance requires the integration of Bayesian prior and likelihood information. Participants in Experiment 1 showed reduced reliance on both information sources after SR, while no significant change was observed after TSD. Participants in Experiment 2 showed reduced reliance on likelihood after SR, especially during morning testing sessions. No accuracy-related impairments resulting from SR and TSD were observed in both experiments. Our findings show SR affects decision-making through altering the way individuals integrate available sources of information. Additionally, the ability to integrate information during SR may be influenced by time of day. Broadly, our findings carry implications for working professionals who are required to make high-stakes decisions on the job, yet consistently receive insufficient sleep due to work schedule demands.

5.
PLoS Comput Biol ; 19(12): e1011707, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38127874

RESUMO

Positive and negative affective states are respectively associated with optimistic and pessimistic expectations regarding future reward. One mechanism that might underlie these affect-related expectation biases is attention to positive- versus negative-valence features (e.g., attending to the positive reviews of a restaurant versus its expensive price). Here we tested the effects of experimentally induced positive and negative affect on feature-based attention in 120 participants completing a compound-generalization task with eye-tracking. We found that participants' reward expectations for novel compound stimuli were modulated in an affect-congruent way: positive affect induction increased reward expectations for compounds, whereas negative affect induction decreased reward expectations. Computational modelling and eye-tracking analyses each revealed that these effects were driven by affect-congruent changes in participants' allocation of attention to high- versus low-value features of compounds. These results provide mechanistic insight into a process by which affect produces biases in generalized reward expectations.


Assuntos
Motivação , Pessimismo , Humanos , Emoções , Generalização Psicológica , Recompensa
6.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34583989

RESUMO

The skeletal muscle L-type Ca2+ channel (CaV1.1) works primarily as a voltage sensor for skeletal muscle action potential (AP)-evoked Ca2+ release. CaV1.1 contains four distinct voltage-sensing domains (VSDs), yet the contribution of each VSD to AP-evoked Ca2+ release remains unknown. To investigate the role of VSDs in excitation-contraction coupling (ECC), we encoded cysteine substitutions on each S4 voltage-sensing segment of CaV1.1, expressed each construct via in vivo gene transfer electroporation, and used in cellulo AP fluorometry to track the movement of each CaV1.1 VSD in skeletal muscle fibers. We first provide electrical measurements of CaV1.1 voltage sensor charge movement in response to an AP waveform. Then we characterize the fluorescently labeled channels' VSD fluorescence signal responses to an AP and compare them with the waveforms of the electrically measured charge movement, the optically measured free myoplasmic Ca2+, and the calculated rate of Ca2+ release from the sarcoplasmic reticulum for an AP, the physiological signal for skeletal muscle fiber activation. A considerable fraction of the fluorescence signal for each VSD occurred after the time of peak Ca2+ release, and even more occurred after the earlier peak of electrically measured charge movement during an AP, and thus could not directly reflect activation of Ca2+ release or charge movement, respectively. However, a sizable fraction of the fluorometric signals for VSDs I, II, and IV, but not VSDIII, overlap the rising phase of charge moved, and even more for Ca2+ release, and thus could be involved in voltage sensor rearrangements or Ca2+ release activation.


Assuntos
Potenciais de Ação/fisiologia , Canais de Cálcio Tipo L/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/química , Acoplamento Excitação-Contração , Ativação do Canal Iônico , Camundongos , Coelhos , Retículo Sarcoplasmático/metabolismo
7.
J Cutan Pathol ; 50(11): 963-970, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37649312

RESUMO

Pilomatricomas (PMs) are common benign adnexal tumors that show a predilection for the head and neck region and are characterized at the molecular level by activating mutations in the beta-catenin (CTNNB1) gene. Giant PMs are a rare histopathological variant, according to the World Health Organization, which are defined by a size greater than 4 cm and are reported to show upregulation of yes-associated protein compared to PMs of typical 1-3 cm size. We describe the case of a 67-year-old man with an 8 cm giant PM involving his temporal scalp, whose PM we characterized by 10X spatial gene expression analysis. This revealed five total transcriptomic clusters, including four distinct clusters within the giant PM, each with a unique transcriptional pattern of hair follicle-related factors, keratin gene expression, and beta-catenin pathway activity.


Assuntos
Doenças do Cabelo , Pilomatrixoma , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Pilomatrixoma/patologia , beta Catenina/genética , beta Catenina/metabolismo , Transcriptoma , Doenças do Cabelo/patologia , Neoplasias Cutâneas/patologia , Perfilação da Expressão Gênica
8.
J Sports Sci Med ; 22(4): 658-666, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38045749

RESUMO

Wearables are lightweight, portable technology devices that are traditionally used to monitor physical activity and workload as well as basic physiological parameters such as heart rate. However recent advances in monitors have enabled better algorithms for estimation of caloric expenditure from heart rate for use in weight loss as well as sport performance. can be used for estimating energy expenditure and nutritional demand. Recently, the military has adopted the use of personal wearables for utilization in field studies for ecological validity of training. With popularity of use, the need for validation of these devices for caloric estimates is needed to assist in work-rest cycles. Thus the purpose of this effort was to evaluate the Polar Grit X for energy expenditure (EE) for use in military training exercises. Polar Grit X Pro watches were worn by active-duty elite male operators (N = 16; age: 31.7 ± 5.0 years, height: 180.1 ± 6.2 cm, weight: 91.7 ± 9.4 kg). Metrics were measured against indirect calorimetry of a metabolic cart and heart rate via a Polar heart rate monitor chest strap while exercising on a treadmill. Participants each performed five 10-minute bouts of running at a self-selected speed and incline to maintain a heart rate within one of five heart rate zones, as ordered and defined by Polar. Polar Grit X Pro watch had a good to excellent interrater reliability to indirect calorimetry at estimating energy expenditure (ICC = 0.8, 95% CI = 0.61-0.89, F (74,17.3) = 11.76, p < 0.0001) and a fair to good interrater reliability in estimating macronutrient partitioning (ICC = 0.49, 95% CI = 0.3-0.65, F (74,74.54) = 2.98, p < 0.0001). There is a strong relationship between energy expenditure as estimated from the Polar Grit X Pro and measured through indirect calorimetry. The Polar Grit X Pro watch is a suitable tool for estimating energy expenditure in free-living participants in a field setting and at a range of exercise intensities.


Assuntos
Militares , Humanos , Masculino , Adulto , Projetos Piloto , Reprodutibilidade dos Testes , Exercício Físico/fisiologia , Metabolismo Energético/fisiologia
9.
J Cutan Pathol ; 49(3): 231-245, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34536035

RESUMO

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.


Assuntos
Dermatologia/normas , Patologia Clínica/normas , Dermatopatias/patologia , Medicina Baseada em Evidências/normas , Humanos , Sociedades Médicas , Estados Unidos
10.
Cogn Emot ; 36(7): 1343-1360, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35929878

RESUMO

Across species, animals have an intrinsic drive to approach appetitive stimuli and to withdraw from aversive stimuli. In affective science, influential theories of emotion link positive affect with strengthened behavioural approach and negative affect with avoidance. Based on these theories, we predicted that individuals' positive and negative affect levels should particularly influence their behaviour when innate Pavlovian approach/avoidance tendencies conflict with learned instrumental behaviours. Here, across two experiments - exploratory Experiment 1 (N = 91) and a preregistered confirmatory Experiment 2 (N = 335) - we assessed how induced positive and negative affect influenced Pavlovian-instrumental interactions in a reward/punishment Go/No-Go task. Contrary to our hypotheses, we found no evidence for a main effect of positive/negative affect on either approach/avoidance behaviour or Pavlovian-instrumental interactions. However, we did find evidence that the effects of induced affect on behaviour were moderated by individual differences in self-reported behavioural inhibition and gender. Exploratory computational modelling analyses explained these demographic moderating effects as arising from positive correlations between demographic factors and individual differences in the strength of Pavlovian-instrumental interactions. These findings serve to sharpen our understanding of the effects of positive and negative affect on instrumental behaviour.


Assuntos
Emoções , Aprendizagem , Animais , Humanos , Aprendizagem/fisiologia , Recompensa , Inibição Psicológica , Afeto
11.
Cogn Affect Behav Neurosci ; 21(5): 993-1009, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33973158

RESUMO

A recent theory proposes that the personality trait openness/intellect is underpinned by differential sensitivity to the reward value of information. This theory draws on evidence that midbrain dopamine neurons respond to unpredicted information gain, mirroring their responses to unpredicted primary rewards. Using a choice task modelled on this seminal work (Experiment 1, N = 139, 69% female), we examined the relation between openness/intellect and willingness to pay for non-instrumental information (i.e., information with no secondary utility). We also assessed whether any such relation was moderated by the dopamine D2 receptor antagonist sulpiride (Experiment 2, N = 164, 100% male). Unexpectedly, most measures of openness/intellect were unrelated to costly information preference in both experiments, and some predicted a decreased willingness to incur a cost for information. In Experiment 2, this cost-dependent association between openness/intellect and information valuation appeared in the placebo condition but not under sulpiride. In addition, participants were more willing to pay for moderately costly information under sulpiride compared to placebo, consistent with a dopaminergic basis to information valuation. Potential refinements to the information valuation theory of openness/intellect are discussed in the light of these and other emerging findings.


Assuntos
Cognição , Recompensa , Sulpirida/farmacologia , Feminino , Humanos , Masculino , Mesencéfalo
12.
Ann Behav Med ; 55(2): 93-102, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33555336

RESUMO

BACKGROUND: Cross-sectional studies have found that the coronavirus disease 2019 (COVID-19) pandemic has negatively affected population-level mental health. Longitudinal studies are necessary to examine trajectories of change in mental health over time and identify sociodemographic groups at risk for persistent distress. PURPOSE: To examine the trajectories of mental distress between March 10 and August 4, 2020, a key period during the COVID-19 pandemic. METHODS: Participants included 6,901 adults from the nationally representative Understanding America Study, surveyed at baseline between March 10 and 31, 2020, with nine follow-up assessments between April 1 and August 4, 2020. Mixed-effects logistic regression was used to examine the association between date and self-reported mental distress (measured with the four-item Patient Health Questionnaire) among U.S. adults overall and among sociodemographic subgroups defined by sex, age, race/ethnicity, household structure, federal poverty line, and census region. RESULTS: Compared to March 11, the odds of mental distress among U.S. adults overall were 1.84 (95% confidence interval [CI] = 1.65-2.07) times higher on April 1 and 1.92 (95% CI = 1.62-2.28) times higher on May 1; by August 1, the odds of mental distress had returned to levels comparable to March 11 (odds ratio [OR] = 0.80, 95% CI = 0.66-0.96). Females experienced a sharper increase in mental distress between March and May compared to males (females: OR = 2.29, 95% CI = 1.85-2.82; males: OR = 1.53, 95% CI = 1.15-2.02). CONCLUSIONS: These findings highlight the trajectory of mental health symptoms during an unprecedented pandemic, including the identification of populations at risk for sustained mental distress.


Assuntos
COVID-19/psicologia , Saúde Mental/tendências , Angústia Psicológica , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente , Autorrelato , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
13.
J Am Acad Dermatol ; 85(4): e209-e233, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33820677

RESUMO

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.


Assuntos
Ceratose Actínica , Fotoquimioterapia , Diclofenaco/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Imiquimode/uso terapêutico , Ceratose Actínica/tratamento farmacológico
14.
J Am Acad Dermatol ; 85(4): 945-955, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34111497

RESUMO

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.


Assuntos
Ceratose Actínica , Criocirurgia , Fluoruracila/uso terapêutico , Humanos , Imiquimode/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia , Guias de Prática Clínica como Assunto
15.
J Cutan Pathol ; 48(7): 842-846, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33326119

RESUMO

BACKGROUND: The histopathological diagnosis of MF is challenging, and there is significant overlap with benign inflammatory processes. Clinical features may be relevant in the assessment of skin biopsies. METHODS: We provided photomicrographs to board-certified dermatopathologists and one hematopathologist with and without accompanying clinical photographs and assessed accuracy and confidence in diagnosing MF. RESULTS: We found that access to clinical photographs improved diagnostic accuracy in both MF and non-MF (distractors); the degree of improvement was significantly higher in the non-MF/distractor category. Across all categories, diagnostic confidence level was higher when clinical images were available. CONCLUSION: These findings suggest that clinical images are useful in making an accurate diagnosis of MF, and may be particularly helpful in ruling it out when an inflammatory disorder is clinically suspected.


Assuntos
Inflamação/patologia , Micose Fungoide/diagnóstico , Fotomicrografia/métodos , Neoplasias Cutâneas/patologia , Adulto , Biópsia/métodos , Dermatologistas/psicologia , Diagnóstico Diferencial , Hematologia/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Micose Fungoide/patologia , Micose Fungoide/ultraestrutura , Variações Dependentes do Observador , Patologistas/psicologia , Competência Profissional/estatística & dados numéricos , Reprodutibilidade dos Testes , Autoimagem , Pele/patologia
16.
Alzheimers Dement ; 17(11): 1808-1817, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34297895

RESUMO

INTRODUCTION: Effective strategies to recruit older adults with mild cognitive impairment (MCI) into nonpharmacological intervention trials are lacking. METHODS: Recruitment for EXERT, a multisite randomized controlled 18-month trial examining the effects of aerobic exercise on cognitive trajectory in adults with amnestic MCI, involved a diverse portfolio of strategies to enroll 296 participants. RESULTS: Recruitment occurred September 2016 through March 2020 and was initially slow. After mass mailings of 490,323 age- and geo-targeted infographic postcards and brochures, recruitment rates increased substantially, peaking at 16 randomizations/month in early 2020. Mass mailings accounted for 52% of randomized participants, whereas 25% were recruited from memory clinic rosters, electronic health records, and national and local registries. Other sources included news broadcasts, public service announcements (PSA), local advertising, and community presentations. DISCUSSION: Age- and geo-targeted mass mailing of infographic materials was the most effective approach in recruiting older adults with amnestic MCI into an 18-month exercise trial.


Assuntos
Amnésia/terapia , Disfunção Cognitiva/terapia , Exercício Físico , Folhetos , Seleção de Pacientes , Idoso , Cognição , Feminino , Humanos , Masculino , Serviços Postais
17.
J Neurosci ; 39(50): 9954-9966, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31676602

RESUMO

Transient receptor potential vanilloid subtype 1 (TRPV1) is a nonselective cationic channel activated by painful stimuli such as capsaicin and noxious heat, and enriched in sensory neurons of the pain pathway. During inflammation, chemical mediators activate protein kinases (such as PKC) that phosphorylate TRPV1 and thereby enhance its function, with consequent increases in nociceptor sensitization. However, the causal relationships between TRPV1 phosphorylation and pathological pain remain unexplored. To directly investigate the roles of one specific TRPV1 phosphorylation event in vivo, we genetically altered a major PKC phosphorylation site, mouse TRPV1 S801, to alanine. The TRPV1 expression pattern in sensory neurons of S801A knock-in (KI) mice was comparable to that in WT controls. However, sensitization of capsaicin-mediated currents after the activation of PKC was substantially impaired in sensory neurons from KI mice. Thermal hyperalgesia induced by PMA or burn injury in KI was identical to WT. Inflammatory thermal hyperalgesia was only marginally attenuated in KI mice. In contrast, PMA-evoked nocifensive responses and sensitization of capsaicin responses were significantly attenuated in the hindpaws of KI mice. Ongoing pain from inflamed masseter muscle was also reduced in KI mice, and was further inhibited by the TRPV1 antagonist AMG9810. These results suggest that PKC-mediated phosphorylation of TRPV1 S801 contributes to inflammation-mediated sensitization of TRPV1 to ligand, but not heat, in vivo Further, this suggests that interference with TRPV1 S801 phosphorylation might represent one potential way to attenuate inflammatory pain, yet spare basal sensitivity and produce fewer side effects than more general TRPV1 inhibition.SIGNIFICANCE STATEMENT Transient receptor potential vanilloid subtype 1 (TRPV1) has been considered a potential target for pain intervention. Global inhibitors of TRPV1 function, however, produce side effects which could compromise their clinical utility. By precisely removing a unique PKC phosphorylation site (TRPV1 S801) in mice through CRISPR/Cas9 editing, we provide in vivo evidence for a highly specific inhibition that leaves basal TRPV1 function intact, yet alleviates some forms of hyperalgesia. These findings support inhibition of TRPV1 S801 phosphorylation as a potential intervention for pain management.


Assuntos
Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Proteína Quinase C/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Temperatura Alta , Inflamação/metabolismo , Camundongos , Camundongos Transgênicos , Medição da Dor , Fosforilação , Estimulação Física
18.
Am J Public Health ; 110(11): 1628-1634, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32941066

RESUMO

Objectives. To assess the impact of the COVID-19 pandemic on mental distress in US adults.Methods. Participants were 5065 adults from the Understanding America Study, a probability-based Internet panel representative of the US adult population. The main exposure was survey completion date (March 10-16, 2020). The outcome was mental distress measured via the 4-item version of the Patient Health Questionnaire.Results. Among states with 50 or more COVID-19 cases as of March 10, each additional day was significantly associated with an 11% increase in the odds of moving up a category of distress (odds ratio = 1.11; 95% confidence interval = 1.01, 1.21; P = .02). Perceptions about the likelihood of getting infected, death from the virus, and steps taken to avoid infecting others were associated with increased mental distress in the model that included all states. Individuals with higher consumption of alcohol or cannabis or with history of depressive symptoms were at significantly higher risk for mental distress.Conclusions. These data suggest that as the COVID-19 pandemic continues, mental distress may continue to increase and should be regularly monitored. Specific populations are at high risk for mental distress, particularly those with preexisting depressive symptoms.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/etnologia , Depressão/epidemiologia , Feminino , Humanos , Seguro Saúde , Masculino , Fumar Maconha/epidemiologia , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Pneumonia Viral/etnologia , SARS-CoV-2 , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
19.
J Am Acad Dermatol ; 82(1): 110-116, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31408683

RESUMO

BACKGROUND: There are too few board-certified dermatologists to treat all patients with skin disease. Primary care physicians often serve at the frontline of skin cancer screening. OBJECTIVE: To compare biopsy use among dermatologist physicians, dermatology advanced practice professionals (APPs), primary care physicians (PCPs), and other nondermatology clinicians. METHODS: Pathology reports, requisition forms, and clinical notes of skin biopsies submitted to our institution during the study period were reviewed. Skin biopsies for inflammatory conditions, cosmetic or functional purposes, and re-excisions were excluded. The number needed to biopsy (NNB) was calculated as the number of biopsied lesions divided by histologically proven skin cancers. RESULTS: The NNB by clinician type was 2.82 for dermatology physicians, 4.69 for APPs, 4.55 for nondermatology PCPs, and 6.55 for other nondermatology clinicians (P < .001). The NNB was significant between clinician groups for nonmelanoma skin cancer (dermatology physicians, 2.00; APPs, 2.71; PCPs, 2.36; and other nondermatology clinicians, 3.47; P < .001) but not for melanoma (dermatology clinicians, 14.33; APPs, 20.78; PCPs, 27.80; and other nondermatology clinicians, 53.56; P = .061). LIMITATIONS: The NNB represents a measure of use but gives no insight into the number of malignant lesions that go unbiopsied and, therefore, undiagnosed. The prevalence of skin cancer varies among dermatology and nondermatology practices. The results are not generalizable to all practice settings. CONCLUSIONS: Dermatology physicians had the lowest NNB of all clinician groups. PCPs performed similarly to dermatology APPs.


Assuntos
Biópsia por Agulha/estatística & dados numéricos , Competência Clínica , Dermatologistas/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Médicos de Atenção Primária/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Adulto , Idoso , Biópsia por Agulha/métodos , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Estados Unidos
20.
Am J Dermatopathol ; 42(7): 530-532, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31688006

RESUMO

Basomelanocytic neoplasms are tumors consisting of elements of both basal cell carcinoma and melanoma. These tumors are exceedingly rare and present a unique challenge as to how the melanoma component should be classified. Due to the paucity of cases, there are no clear-cut evidence-based guidelines as to how these tumors should be staged and which treatment options provide the optimal outcome. We present 2 separate patients with similar cases of colonizing basomelanocytic tumors that were treated in drastically different ways, highlighting the differing approaches to treatment. We discuss theses treatment modalities and the challenges inherent to diagnosing and treating basomelanocytic neoplasms.


Assuntos
Carcinoma Basocelular/patologia , Melanoma/patologia , Neoplasias Complexas Mistas/patologia , Neoplasias Cutâneas/patologia , Idoso , Feminino , Humanos , Masculino
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