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Personalized medicine promises the ability to improve patient outcomes by tailoring treatment recommendations to the likelihood that any given patient will respond well to a given treatment. It is important that predictions of treatment response be validated and replicated in independent data to support their use in clinical practice. In this paper, we propose and test an approach for validating predictions of individual treatment effects with continuous outcomes across samples that uses matching in a test (validation) sample to match individuals in the treatment and control arms based on their predicted treatment response and their predicted response under control. To examine the proposed validation approach, we conducted simulations where test data is generated from either an identical, similar, or unrelated process to the training data. We also examined the impact of nuisance variables. To demonstrate the use of this validation procedure in the context of predicting individual treatment effects in the treatment of alcohol use disorder, we apply our validation procedure using data from a clinical trial of combined behavioral and pharmacotherapy treatments. We find that the validation algorithm accurately confirms validation and lack of validation, and also provides insights into cases where test data were generated under similar, but not identical conditions. We also show that the presence of nuisance variables detrimentally impacts algorithm performance, which can be partially reduced though the use of variable selection methods. An advantage of the approach is that it can be widely applied to different predictive methods.
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The NIMH-funded Multilevel Community-Based Mental Health Intervention to Address Structural Inequities and Adverse Disparate Consequences of COVID-19 Pandemic on Latinx Immigrants and African Refugees study aims to advance the science of multilevel interventions to reduce the disparate, adverse mental health, behavioral, and socioeconomic consequences of the COVID-19 pandemic that are a result of complex interactions between underlying structural inequities and barriers to health care. The study tests three nested levels of intervention: 1) an efficacious 4-month advocacy and mutual learning model (Refugee and Immigrant Well-being Project, RIWP); 2) engagement with community-based organizations (CBOs); and 3) structural policy changes enacted in response to the pandemic. This community-based participatory research (CBPR) study builds on long-standing collaboration with five CBOs. By including 240 Latinx immigrants and 60 African refugees recruited from CBO partners who are randomly assigned to treatment-as-usual CBO involvement or the RIWP intervention and a comparison group comprised of a random sample of 300 Latinx immigrants, this mixed methods longitudinal waitlist control group design study with seven time points over 36 months tests the effectiveness of the RIWP intervention and engagement with CBOs to reduce psychological distress, daily stressors, and economic precarity and increase protective factors (social support, access to resources, English proficiency, cultural connectedness). The study also tests the ability of the RIWP intervention and engagement with CBOs to increase access to the direct benefits of structural interventions. This paper reports on the theoretical basis, design, qualitative and quantitative analysis plan, and power for the study.
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COVID-19 , Emigrantes e Imigrantes , Saúde Mental , Refugiados , Humanos , COVID-19/epidemiologia , Hispânico ou Latino , Pandemias , Refugiados/psicologia , População Negra , Disparidades nos Níveis de SaúdeRESUMO
This mixed method study developed multiple question types to understand and measure women's perceived benefit from adjuvant endocrine therapy. We hypothesis that patients do not understand this benefit and sought to develop the questions needed to test this hypothesis and obtain initial patient estimates. From 8/2022 to 3/2023, qualitative interviews focused on assessing and modifying 9 initial varied question types asking about the overall survival (OS) benefit from adjuvant endocrine therapy. Subsequent focus groups modified and selected the optimal questions. Patients' self-assessment of their OS benefit was compared to their individualized PREDICT model results. Fifty-three patients completed the survey; 42% Hispanic, 30% rural, and 47% with income < $39,999 per year. Patients reported adequate health care literacy (61.5%) and average confidence about treatment and medication decisions 49.4 (95% CI 24.4-59.5). From the original 9 questions, 3 modified questions were ultimately found to capture patients' perception of this OS benefit, focusing on graphical and prose styles. Patients estimated an OS benefit of 42% compared to 4.4% calculated from the PREDICT model (p < 0.001). In this group with considerable representation from ethnic minority, rural and low-income patients, qualitative data showed that more than one modality of question type was needed to clearly capture patients' understanding of treatment benefit. Women with breast cancer significantly overestimated their 10-year OS benefit from adjuvant endocrine therapy compared to the PREDICT model.
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Neoplasias da Mama , Humanos , Feminino , Projetos Piloto , Neoplasias da Mama/tratamento farmacológico , Etnicidade , Grupos Minoritários , Terapia CombinadaRESUMO
OBJECTIVE: Precision medicine is an area with great potential for mental health, but has made limited gains prognostically in predicting effective treatments. For refugees exposed to violence, culture may be a crucial factor in predicting treatment outcomes. METHOD: For this study, 290 participants from three regions (Afghanistan, the Great Lakes region of Africa, and Iraq and Syria) participated in a randomized controlled trial of an advocacy-based intervention. Emotional distress symptoms were measured prior to intervention, midintervention (3 months), postintervention (6 months), and follow-up (6 months after the end of intervention). Number of traumatic events, resource access, social support, and English proficiency were tested for potential predictive effects on intervention outcome. RESULTS: Multilevel generalized linear models revealed that Afghans' (B = -0.259, SE = 0.108, p = .013), and Great Lakes Africans' (B = -0.116, SE = 0.057, p = .042) emotional distress symptoms improved as a function of the intervention, while Iraqis and Syrians showed no intervention effects. For Afghans, English proficiency (B = -0.453, SE = 0.157, p < .01) and social support (B = -0.179, SE = 0.086, p = .037) were most strongly correlated to emotional distress, while for Africans, resource access (B = -0.483, SE = 0.082, p < .001) and social support (B = -0.100, SE = 0.048, p = .040) were the strongest predictors of emotional distress. CONCLUSIONS: Response to advocacy-based interventions and active ingredients may be influenced by culture; findings have implications for refugees and precision medicine. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Saúde Mental , Refugiados , Humanos , Avaliação de Resultados em Cuidados de Saúde , Medicina de Precisão , Refugiados/psicologia , Estresse Psicológico/psicologia , População AfricanaRESUMO
BACKGROUND: Calprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland. METHODS: Calprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models. RESULTS: Overall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001). CONCLUSIONS: Serum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations. TRIAL REGISTRATION: NCT04581135.
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COVID-19 , Hipertensão , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Críticos , Hospitais Universitários , Complexo Antígeno L1 Leucocitário , PulmãoRESUMO
BACKGROUND: Effective COVID-19 vaccines have been available since early 2021 yet many Americans refuse or delayed uptake. As of mid-2022, still around 30% of US adults remain unvaccinated against COVID-19. The majority (81%) of these unvaccinated adults say they will "definitely not" be getting the COVID-19 vaccine. Understanding the determinants of COVID-19 vaccine uptake is critical to reducing death and illness from the virus, as well as to inform future vaccine efforts, such as the more recent bivalent (omicron) booster. OBJECTIVE: This study aimed to expand our understanding of psychosocial determinants of COVID-19 vaccine uptake. We focus on both COVID-19-specific factors, such as COVID-19 conspiracy beliefs, as well as more global personality attributes such as dogmatism, reactance, gender roles, political beliefs, and religiosity. METHODS: We conducted a web-based survey in mid-2021 of a representative sample of 1376 adults measuring both COVID-19-specific beliefs and attitudes, as well as global personality attributes. COVID-19 vaccination status is reported at 3 levels: vaccinated; unvaccinated-may-get-it; unvaccinated-hard-no. RESULTS: Our analyses focused on the correlation of COVID-19 vaccination status with 10 psychosocial attributes: COVID-19-specific conspiracy theory beliefs; COVID-19 vaccine misinformation; COVID-19-related Rapture beliefs; general antivaccination beliefs; trait reactance; trait dogmatism; belief in 2020 election fraud; belief in a QAnon conspiracy; health care system distrust; and identification with traditional gender roles. We used a multivariate analysis of covariance to examine mean differences across vaccine status groups for each of the correlates while holding constant the effects of age, gender, race, income, education, political party, and Evangelicalism. Across the 10 psychosocial correlates, several different response scales were used. To allow for comparison of effects across correlates, measures of effect size were computed by converting correlates to z scores and then examining adjusted mean differences in z scores between the groups. We found that all 10 psychosocial variables were significantly associated with vaccination status. After general antivaccination beliefs, COVID-19 misinformation beliefs and COVID-19 conspiracy beliefs had the largest effect on vaccine uptake. CONCLUSIONS: The association of these psychosocial factors with COVID-19 vaccine hesitancy may help explain why vaccine uptake has not shifted much among the unvaccinated-hard-no group since vaccines became available. These findings deepen our understanding of those who remain resistant to getting vaccinated and can guide more effective tailored communications to reach them. Health communication professionals may apply lessons learned from countering related beliefs and personality attributes around issues such as climate change and other forms of vaccine hesitancy. For example, using motivational interviewing strategies that are equipped to handle resistance and provide correct information in a delicate manner that avoids reactance.
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Purpose: This mixed methods study developed multiple question types to understand and measure women's perceived benefit from adjuvant endocrine therapy. We hypothesis that patients do not understand this benefit and sought to develop the questions needed to test this hypothesis and obtain initial patient estimates. Methods: From 8/2022 to 3/2023, qualitative interviews focused on assessing and modifying 9 initial varied question types asking about the overall survival (OS) benefit from adjuvant endocrine therapy. Subsequent focus groups modified and selected the optimal questions. Patients' self-assessment of their OS benefit was compared to their individualized PREDICT model results. Results: Fifty-three patients completed the survey; 42% Hispanic, 30% rural, and 47% with income <$39,999 per year. Patients reported adequate health care literacy (61.5%) and average confidence about treatment and medication decisions 49.4 (95% CI 24.4-59.5). From the original 9 questions, 3 modified questions were ultimately found to capture patients' perception of this OS benefit, focusing on graphical and prose styles. Patients estimated an OS benefit of 42% compared to 4.4% calculated from the PREDICT model (p < 0.001). Conclusion: In this group with considerable representation from ethnic minority, rural and low-income patients, qualitative data showed that more than one modality of question type was needed to clearly capture patients' understanding of treatment benefit. Women with breast cancer significantly overestimated their 10-year OS benefit from adjuvant endocrine therapy compared to the PREDICT model.
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BACKGROUND: Web-based tailored interventions offer rich opportunities for improved access to and personalization of behavioral interventions. However, despite the promise of this approach, the engagement and underrepresentation of minority groups remain major issues. OBJECTIVE: This study evaluated whether engagement (log-in status and log-in duration) with different types of tailored behavioral content from the Families Improving Together for weight loss web-based intervention was associated with changes in moderate to vigorous physical activity (MVPA) among African American families with overweight or obesity. METHODS: Parent-adolescent dyads were randomized to a web-based tailored intervention or web-based health education comparison program. The web-based intervention (N=119) was completed by parents and targeted 6 weight-related behaviors to support their adolescent children's weight loss goals (session contents included energy balance, fast food, fruits and vegetables, physical activity [PA], sedentary behavior, and sweetened beverages). MVPA was measured using accelerometers at baseline and after the intervention. RESULTS: Using a hierarchical approach, the log-in status and duration for each web-based session were used to evaluate the additive effects of engagement with different types of tailored behavioral content on MVPA after the web-based intervention. Among parents, logging in to the PA session was not associated with greater MVPA (B=-12.561, 95% CI -18.759 to -6.367), but MVPA increased with greater log-in duration for the PA (B=0.008, 95% CI 0.004-0.012) and sedentary behavior (B= 0.008, 95% CI 0.004-0.012) sessions. These results suggest that parents who logged in to the PA session had lower MVPA, but MVPA increased with greater log-in duration for the PA and sedentary behavior sessions. These associations remained even after accounting for engagement with other content sessions. However, these engagement effects did not translate to the adolescents. CONCLUSIONS: The results of this study highlight the need to disentangle the impact of engagement with different tailored content to improve the efficacy of tailored web-based interventions, especially for promoting PA in African American families. TRIAL REGISTRATION: ClinicalTrials.gov NCT01796067; https://clinicaltrials.gov/ct2/show/NCT01796067.
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Exercício Físico , Redução de Peso , Criança , Adolescente , Humanos , Pais , Promoção da Saúde/métodos , Terapia ComportamentalRESUMO
BACKGROUND AND AIMS: Previous findings have been equivocal as to whether a single-nucleotide polymorphism (rs2832407) in GRIK1, which encodes a glutamate receptor subunit, moderates the effects of topiramate treatment for drinking reduction. We leveraged intensive longitudinal data to provide greater precision and allow an examination of intermediate outcomes addressing this question. We used data from a randomized controlled trial (RCT) to test the hypotheses that topiramate treatment reduces daily heavy drinking, desire to drink and positive alcohol expectancies and that these effects are stronger in rs2832407*C-allele homozygotes. DESIGN: Secondary data analysis of a randomized controlled trial. SETTING: University of Pennsylvania Treatment Research Center in the United States. PARTICIPANTS/CASES: Participants were 164 individuals (70.1% male, mean age = 51.42, 36.0% rs2832407*C-allele homozygotes) who sought to reduce or stop drinking. INTERVENTION AND COMPARATOR: Participants were assigned to medication (topiramate or placebo), with stratification by genotype group (CC versus AA/AC) and treatment goal (reduce versus abstain). MEASUREMENTS: During the 12-week treatment period, participants completed daily interactive voice response (IVR) surveys. FINDINGS: On any given day during treatment, participants who received topiramate had lower odds of IVR-reported heavy drinking [odds ratio (OR) = 0.259, b (standard error, SE) = -1.351 (0.334), P < 0.001] and lower levels of desire to drink [b (SE) = -0.323 (0.122), P = 0.009] and positive alcohol expectancies [b (SE) = -0.347 (0.138), P = 0.013] than those who received placebo. Participants who received topiramate also reported greater reductions in positive alcohol expectancies during the first 2 weeks of treatment than those who received placebo [b (SE) = -0.028 (0.008), P = 0.001], but topiramate did not impact the daily rate of change in heavy drinking or desire to drink. Genotype did not moderate the effects of topiramate on any outcomes examined (P > 0.05). CONCLUSIONS: Topiramate is an effective medication for individuals seeking to reduce heavy drinking. The effects are not moderated by the single-nucleotide polymorphism rs2832407.
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Alcoolismo , Masculino , Humanos , Feminino , Alcoolismo/genética , Topiramato/uso terapêutico , Frutose/uso terapêutico , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/genética , Genótipo , Etanol , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: The intrinsic electrical material properties of the laminar components of the mammalian peripheral nerve bundle are important parameters necessary for the accurate simulation of the electrical interaction between nerve fibers and neural interfaces. Improvements in the accuracy of these parameters improve the realism of the simulation and enables realistic screening of novel devices used for extracellular recording and stimulation of mammalian peripheral nerves. This work aims to characterize these properties for mammalian peripheral nerves to build upon the resistive parameter set established by Weerasuriya et al. in 1984 for amphibian somatic peripheral nerves (frog sciatic nerve) that is currently used ubiquitously in the in-silico peripheral nerve modeling community. METHODS: A custom designed characterization chamber was implemented and used to measure the radial and longitudinal impedance between 10 mHz and 50 kHz of freshly excised canine vagus nerves using four-point impedance spectroscopy. The impedance spectra were parametrically fitted to an equivalent circuit model to decompose and estimate the components of the various laminae. Histological sections of the electrically characterized nerves were then made to quantify the geometry and laminae thicknesses of the perineurium and epineurium. These measured values were then used to calculate the estimated intrinsic electrical properties, resistivity and permittivity, from the decomposed resistances and reactances. Finally, the estimated intrinsic electrical properties were used in a finite element method (FEM) model of the nerve characterization setup to evaluate the realism of the model. RESULTS: The geometric measurements were as follows: nerve bundle (1.6 ± 0.6 mm), major nerve fascicle diameter (1.3 ± 0.23 mm), and perineurium thickness (13.8 ± 2.1 µm). The longitudinal resistivity of the endoneurium was estimated to be 0.97 ± 0.05 Ωm. The relative permittivity and resistivity of the perineurium were estimated to be 2018 ± 391 and 3.75 kΩm ± 981 Ωm, respectively. The relative permittivity and resistivity of the epineurium were found to be 9.4 × 106 ± 8.2 × 106 and 55.0 ± 24.4 Ωm, respectively. The root mean squared (RMS) error of the experimentally obtained values when used in the equivalent circuit model to determine goodness of fit against the measured impedance spectra was found to be 13.0 ± 10.7 Ω, 2.4° ± 1.3°. The corner frequency of the perineurium and epineurium were found to be 2.6 ± 1.0 kHz and 368.5 ± 761.9 Hz, respectively. A comparison between the FEM model in-silico impedance experiment against the ex-vivo methods had a RMS error of 159.0 ± 95.4 Ω, 20.7° ± 9.8°. CONCLUSION: Although the resistive values measured in the mammalian nerve are similar to those of the amphibian model, the relative permittivity of the laminae bring new information about the reactance and the corner frequency (frequency at peak reactance) of the peripheral nerve. The measured and estimated corner frequency are well within the range of most bioelectric signals, and are important to take into account when modeling the nerve and neural interfaces.
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Nervos Periféricos , Nervo Isquiático , Animais , Cães , Nervos Periféricos/fisiologia , Nervo Isquiático/fisiologia , Convulsões , MamíferosRESUMO
Physical activity (PA) plays an integral role in reducing risk for the leading causes of death and has also been shown to buffer stress. Based on the stress-buffering hypothesis, the present study examined whether protective factors (self-efficacy and informal social control) buffered the effects of perceived stress on PA over time. Secondary data analyses of female African American caregivers (N = 143) were conducted using data from the Families Improving Together (FIT) trial. Validated measures of stressors and protective factors were assessed at baseline. Light PA and moderate-to-vigorous PA were assessed using seven-day accelerometry estimates over sixteen weeks. Multilevel growth modeling was used to assess whether protective factors moderated the effects of perceived stress on PA outcomes across 16 weeks. There was a significant two-way interaction between informal social control and time (B = 0.40, SE = 0.17, p = .019) such that higher informal social control was positively associated with MVPA over time. There was a marginal three-way interaction (B = -18.90, SE = 10.31, p = .067) such that stress was associated with greater LPA at baseline under conditions of high but not low self-efficacy. This study provides preliminary support that social factors may be important for maintaining MVPA regardless of stress levels, while cognitive resources may be more important to target for influencing LPA engagement under conditions of high stress.
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Negro ou Afro-Americano , Exercício Físico , Feminino , Humanos , Acelerometria , Exercício Físico/psicologia , Fatores de ProteçãoRESUMO
CONTEXT: The high prevalence of psychiatric disorders among people in prison is well documented, and several hypotheses have been proposed to explain this overrepresentation. In France, the decrease in the number of people found by the judge to be not criminally responsible on account of mental disorder after a psychiatric expertise could play a crucial role. The Château-Thierry prison is a high-security correctional facility where prisoners whose integration into a "standard" prison is complicated because of behavioural problems, reside. We conducted the first study to describe the judicial and healthcare trajectories of people incarcerated in this facility. METHOD: All the people incarcerated in the Château-Thierry prison between May and September 2019 were included in this cross-sectional study. In addition to sociodemographic characteristics, data on the psychiatric care before and during incarceration as well as information on the judicial and prison history were collected. We also analyzed all the pre-sentencing psychiatric reports in order to collect the degree of discernment determined by the psychiatrist expert for each included individual. RESULTS: Sixty-eight (97%) of the 70 people detained at the Château-Thierry prison during the study period were included and 92 pre-sentencing psychiatric reports were analyzed. The population studied was exclusively male, with an average age of 40 years, low socio-economic status and frequent criminal history (79%). About half of them (46%) had already been hospitalized in a psychiatric community hospital prior to incarceration, and 79% have been hospitalized in a psychiatric facility during their incarceration. Disciplinary sanctions were frequent (72%) as well as convictions for offenses committed while in prison (57%). When at least one pre-sentencing psychiatric report was carried out (29 persons had a single psychiatric forensic evaluation and 27 ones had multiple evaluations), at least one psychiatric expert had concluded to a diminished (but not lack of) criminal responsibility in almost half of the cases (44%). CONCLUSION: This study shows the extent to which people incarcerated in the Château-Thierry prison are affected by psychiatric disorders. It also highlights the difficulties of coping with the prison environment for people suffering from psychiatric disorders. Finally, it raises the question of the lack of diversion programs for the individuals in France with mental health problems whose responsibility has been considered as full or diminished.
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Criminosos , Transtornos Mentais , Prisioneiros , Humanos , Masculino , Adulto , Prisões , Estudos Transversais , Prisioneiros/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Criminosos/psicologiaRESUMO
Mechanisms of behavior change are the processes through which interventions are hypothesized to cause changes in outcomes. Latent growth curve mediation models (LGCMM) are recommended for investigating the mechanisms of behavior change because LGCMM models establish temporal precedence of change from the mediator to the outcome variable. The Correlated Augmented Mediation Sensitivity Analyses (CAMSA) App implements sensitivity analysis for LGCMM models to evaluate if a mediating path (mechanism) is robust to potential confounding variables. The CAMSA approach is described and applied to simulated data, and data from a research study exploring a mechanism of change in the treatment of substance use disorder.
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BACKGROUND: The stimulation and recording performance of implanted neural interfaces are functions of the physical and electrical characteristics of the neural interface, its electrode material and structure. Therefore, rapid optimization of such characteristics is becoming critical in most clinical and research studies. This paper describes the development of an upgraded 3D printed cuff electrode shell design containing a novel intrinsically conductive polymer (ICP) for stimulation and recording of peripheral nerve fibers. METHODS: A 3D stereolithography (SLA) printer was used to print a scalable, custom designed, C-cuff electrode and I-beam closure for accurate, rapid implementation. A novel contact consisting of a percolated carbon graphite base electrodeposited with an intrinsically conductive polymer (ICP), poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) produced a PEDOT:PSS + carbon black (CB) matrix that was used to form the electrochemical interface on the structure. Prototype device performance was tested both in-vitro and in-vivo for electrical chemical capacity, electrochemical interfacial impedance, surgical handling, and implantability. The in-vivo work was performed on the sciatic nerve of 25 anesthetized Sprague Dawley rats to demonstrate recording and stimulating ability. RESULTS: Prototypes of different spatial geometries and number of contacts (bipolar, tripolar, and tetrapolar) were designed. The design was successfully printed with inner diameters down to 500 µm. Standard bipolar and tripolar cuffs, with a 1.3 mm inner diameter (ID), 0.5 mm contact width, 1.0 mm pitch, and a 1.5 mm end distance were used for the functional tests. This geometry was appropriate for placement on the rat sciatic nerve and enabled in-vivo testing in anesthetized rats. The contacts on the standard bipolar electrode had an area of 2.1 × 10-2 cm2 . Cyclic voltammetry on ICP coated and uncoated graphite contacts showed that the ICP increased the average charge storage capacity (CSC) by a factor of 30. The corresponding impedance at 1 Hz was slightly above 1 kΩ, a 99.99% decrease from 100 kΩ in the uncoated state. The statistical comparison of the pre- versus post-stimulation impedance measurements were not significantly different (p-value > 0.05). CONCLUSIONS: The new cuff electrode enables rapid development of cost-effective functional stimulation devices targeting nerve bundles less than 1.0 mm in diameter. This allows for recording and modulation of a low-frequency current targeted within the peripheral nervous system.
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Carbono , Grafite , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Eletrodos , Eletrodos Implantados , Polímeros/química , Ratos , Ratos Sprague-Dawley , Fuligem , EstereolitografiaRESUMO
BACKGROUND: In-silico experiments used to optimize and inform how peripheral nerve based electrode designs perform hold the promise of greatly reducing the guesswork with new designs as well as the number of animals used to identify and prove promising designs. Given adequate realism, in-silico experiments offer the promise of identifying putative mechanisms that further inform exploration of novel stimulation and recording techniques and their interactions with bioelectric phenomena. However, despite using validated nerve fiber models, when applied to the more complex case of an implanted extracellular electrode, the in-silico experiments often do not compare quantitatively with the results of experiments conducted in in-vivo experiments. This suggests that the accuracy/realism of the environment and the lamination of the nerve bundle plays an important role in this discrepancy. This paper describes the sensitivity of in-silico models to the electrical parameter estimates and volume conductor type used. METHODS: In-vivo work was performed on rat vagus nerves (N = 2) to characterize the strength-duration curve for various peaks identified in a compound nerve action potential (CAP) measured via a needle electrode. The vagus nerve has several distinct populations of nerve fiber calibers and types. Recruitment of a fiber caliber/type generates distinct peaks that can be identified, and whose conduction delay correlates to a conduction velocity. Peaks were identified by their recruitment thresholds and associated to their conduction velocities by the conduction delays of their peaks. An in-silico analog of the in-vivo experiment was constructed and experiments were run at the two extreme volume conductor cases: (1) The nerve in-saline, and (2) the nerve in-air. The specifically targeted electrical parameters were extraneural environment (in-air versus saline submersion), the resistivity (ρ) of the epineurium and perineurium, and the relative permittivity (εr ) of those same tissues. A time varying finite element method (FEM) model of the potential distribution vs time was quantified and projected onto a modified McIntyre, Richardson, and Grill (MRG), myelinated spinal nerve, active fiber model in NEURON to identify the threshold of activation as a function of stimulus pulse amplitude versus pulse width versus fiber diameter. The in-silico results were then compared to the in-vivo results. RESULTS: The finite element method simulations spanned two macro environments: in-saline and in-air. For these environments, the resistivities for low and high frequencies as well as two different permittivity cases were used. Between these 8 cases unique cases it was found that the most accurate combination of those variables was the in-air environment for low-frequency resistivity (ρ0 ) and ex-vivo a measured permittivity (εr,measured ) from unpublished ex-vivo experiments in canine vagal nerve, achieving a high degree of convergence (r2 = 0.96). As the in-vivo work was conducted in in-air, the in-air boundary condition test case was convergent with the in-silico results. CONCLUSIONS: The results of this investigation suggest that increasing realism in simulations begets more accurate predictions. Of particular importance are (ρ) and extraneural environment, with reactive electrical parameters becoming important for input waveforms with energy in higher frequencies.
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Modelos Neurológicos , Nervos Periféricos , Animais , Simulação por Computador , Cães , Estimulação Elétrica , Eletrodos Implantados , Fibras Nervosas Mielinizadas/fisiologia , Nervos Periféricos/fisiologia , RatosRESUMO
OBJECTIVE: Motivation is a barrier to physical activity (PA) among African American (AA) women, but past studies have implemented a "one-size-fits-all" approach and have not addressed differences in autonomous motivation. This pilot randomized controlled trial assessed the preliminary efficacy of "Developing Real Incentives and Volition for Exercise," a community- and theory-based intervention, which evaluated whether a motivationally matched (vs. a nonmatched) intervention increases daily total PA. METHOD: In total, 68 AA women (50.72 ± 13.66 years; 86.8% with obesity) were randomized to an 8-week challenge-focused program (targeted toward high autonomous motivation) or rewards-focused program (targeted toward low autonomous motivation). Randomization was stratified by baseline autonomous motivation. FitBits were used during the intervention to promote self-monitoring (both programs) and social connectedness (challenge program only). RESULTS: Both programs retained ≥ 80% of participants. Process evaluation revealed high attendance, dose, and fidelity (both programs). However, contrary to expectations, across all motivational levels (low and high autonomous), the challenge-focused intervention resulted in a greater increase in total daily PA (primary outcome), with an average increase of 17.9 min in the challenge-focused intervention versus an average decrease of 8.55 min in the rewards-focused intervention. An exploratory follow-up analysis revealed that engagement with the FitBit mobile app predicted greater PA at postintervention in the challenge-focused program. CONCLUSIONS: A team-based approach targeting social connectedness, enjoyment of PA, and positive intragroup competition is a promising approach for promoting PA among AA women. These findings are used to guide a discussion on best practices for engaging AA women in future behavioral interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Assuntos
Negro ou Afro-Americano , Motivação , Humanos , Feminino , Volição , Projetos Piloto , Exercício FísicoRESUMO
BACKGROUND: Few intervention studies have integrated cultural tailoring, parenting, behavioral, and motivational strategies to address African American adolescent weight loss. PURPOSE: The Families Improving Together (FIT) for Weight Loss trial was a randomized group cohort study testing the efficacy of a cultural tailoring, positive parenting, and motivational intervention for weight loss in overweight African American adolescents (N = 241 adolescent/caregiver dyads). METHODS: The trial tested an 8-week face-to-face group motivational plus family weight loss program (M + FWL) compared with a comprehensive health education control program. Participants were then rerandomized to an 8-week tailored or control online program to test the added effects of the online intervention on reducing body mass index and improving physical activity (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA]), and diet. RESULTS: There were no significant intervention effects for body mass index or diet. There was a significant effect of the group M + FWL intervention on parent LPA at 16 weeks (B = 33.017, SE = 13.115, p = .012). Parents in the group M + FWL intervention showed an increase in LPA, whereas parents in the comprehensive health education group showed a decrease in LPA. Secondary analyses using complier average causal effects showed a significant intervention effect at 16 weeks for parents on MVPA and a similar trend for adolescents. CONCLUSIONS: While the intervention showed some impact on physical activity, additional strategies are needed to impact weight loss among overweight African American adolescents.
Assuntos
Negro ou Afro-Americano , Programas de Redução de Peso , Adolescente , Estudos de Coortes , Humanos , Sobrepeso/terapia , Redução de PesoRESUMO
Free-living amoebae often harbor obligate intracellular bacterial symbionts. Amoebophilus (A.) asiaticus is a representative of a lineage of amoeba symbionts in the phylum Bacteroidota. Here, we analyse the transcriptome of A. asiaticus strain 5a2 at four time points during its infection cycle and replication within the Acanthamoeba host using RNA sequencing. Our results reveal a dynamic transcriptional landscape throughout different A. asiaticus life cycle stages. Many intracellular bacteria and pathogens utilize eukaryotic-like proteins (ELPs) for host cell interaction and the A. asiaticus 5a2 genome shows a particularly high abundance of ELPs. We show the expression of all genes encoding ELPs and found many ELPs to be differentially expressed. At the replicative stage of A. asiaticus, ankyrin repeat proteins and tetratricopeptide/Sel1-like repeat proteins were upregulated. At the later time points, high expression levels of a type 6 secretion system that likely prepares for a new infection cycle after lysing its host, were found. This study reveals comprehensive insights into the intracellular lifestyle of A. asiaticus and highlights candidate genes for host cell interaction. The results from this study have implications for other intracellular bacteria such as other amoeba-associated bacteria and the arthropod symbionts Cardinium forming the sister lineage of A. asiaticus.
Assuntos
Amoeba , Amoeba/genética , Animais , Bactérias/genética , Bacteroidetes/genética , Estágios do Ciclo de Vida , SimbioseRESUMO
There is an increased interest in the use of personalized medicine approaches in the prevention or treatment of obesity, however, few studies have used these approaches to identify individual differences in treatment effects. The current study demonstrates the use of the predicted individual treatment effects framework to test for individual differences in the effects of the ACTION-PAC intervention, which targeted the treatment and prevention of obesity in a high school setting. We show how methods for personalized medicine can be used to test for significant individual differences in responses to an intervention and we discuss the potential and limitations of these methods. In our example, 25% of students in the preventive intervention, were predicted to have their BMI z-score reduced by 0.39 or greater, while at other end of the spectrum, 25% were predicted to have their BMI z-score increased by 0.09 or more. In this paper, we demonstrate and discuss the process of using methods for personalized medicine with interventions targeting adiposity and discuss the lessons learned from this application. Ultimately, these methods have the potential to be useful for clinicians and clients in choosing between treatment options, however they are limited in their ability to help researchers understand the mechanisms underlying these predictions.