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OBJECTIVES: The purpose of the present study was to investigate the pitch accuracy of vocal singing in children with severe to profound hearing loss who use bilateral cochlear implants (CIs) or bimodal devices [CI at one ear and hearing aid (HA) at the other] in comparison to similarly-aged children with normal-hearing (NH). DESIGN: The participants included four groups: (1) 26 children with NH, (2) 13 children with bimodal devices, (3) 31 children with bilateral CIs that were implanted sequentially, and (4) 10 children with bilateral CIs that were implanted simultaneously. All participants were aged between 7 and 11 years old. Each participant was recorded singing a self-chosen song that was familiar to him or her. The fundamental frequencies (F0) of individual sung notes were extracted and normalized to facilitate cross-subject comparisons. Pitch accuracy was quantified using four pitch-based metrics calculated with reference to the target music notes: mean note deviation, contour direction, mean interval deviation, and F0 variance ratio. A one-way ANOVA was used to compare listener-group difference on each pitch metric. A principal component analysis showed that the mean note deviation best accounted for pitch accuracy in vocal singing. A regression analysis examined potential predictors of CI children's singing proficiency using mean note deviation as the dependent variable and demographic and audiological factors as independent variables. RESULTS: The results revealed significantly poorer performance on all four pitch-based metrics in the three groups of children with CIs in comparison to children with NH. No significant differences were found among the three CI groups. Among the children with CIs, variability in the vocal singing proficiency was large. Within the group of 13 bimodal users, the mean note deviation was significantly correlated with their unaided pure-tone average thresholds (r = 0.582, p = 0.037). The regression analysis for all children with CIs, however, revealed no significant demographic or audiological predictor for their vocal singing performance. CONCLUSION: Vocal singing performance in children with bilateral CIs or bimodal devices is not significantly different from each other on a group level. Compared to children with NH, the pediatric bimodal and bilateral CI users, in general, demonstrated significant deficits in vocal singing ability. Demographic and audiological factors, known from previous studies to be associated with good speech and language development in prelingually-deafened children with CIs, were not associated with singing accuracy for these children.
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Implante Coclear , Implantes Cocleares , Auxiliares de Audição , Canto , Percepção da Fala , Criança , Feminino , Audição , Humanos , MasculinoRESUMO
BACKGROUND: The traditional model of promotion and tenure in the health professions relies heavily on formal scholarship through teaching, research, and service. Institutions consider how much weight to give activities in each of these areas and determine a threshold for advancement. With the emergence of social media, scholars can engage wider audiences in creative ways and have a broader impact. Conventional metrics like the h-index do not account for social media impact. Social media engagement is poorly represented in most curricula vitae (CV) and therefore is undervalued in promotion and tenure reviews. OBJECTIVE: The objective was to develop crowdsourced guidelines for documenting social media scholarship. These guidelines aimed to provide a structure for documenting a scholar's general impact on social media, as well as methods of documenting individual social media contributions exemplifying innovation, education, mentorship, advocacy, and dissemination. METHODS: To create unifying guidelines, we created a crowdsourced process that capitalized on the strengths of social media and generated a case example of successful use of the medium for academic collaboration. The primary author created a draft of the guidelines and then sought input from users on Twitter via a publicly accessible Google Document. There was no limitation on who could provide input and the work was done in a democratic, collaborative fashion. Contributors edited the draft over a period of 1 week (September 12-18, 2020). The primary and secondary authors then revised the draft to make it more concise. The guidelines and manuscript were then distributed to the contributors for edits and adopted by the group. All contributors were given the opportunity to serve as coauthors on the publication and were told upfront that authorship would depend on whether they were able to document the ways in which they met the 4 International Committee of Medical Journal Editors authorship criteria. RESULTS: We developed 2 sets of guidelines: Guidelines for Listing All Social Media Scholarship Under Public Scholarship (in Research/Scholarship Section of CV) and Guidelines for Listing Social Media Scholarship Under Research, Teaching, and Service Sections of CV. Institutions can choose which set fits their existing CV format. CONCLUSIONS: With more uniformity, scholars can better represent the full scope and impact of their work. These guidelines are not intended to dictate how individual institutions should weigh social media contributions within promotion and tenure cases. Instead, by providing an initial set of guidelines, we hope to provide scholars and their institutions with a common format and language to document social media scholarship.
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Bolsas de Estudo/normas , Ocupações em Saúde/educação , Mídias Sociais/normas , HumanosRESUMO
[This corrects the article DOI: 10.2196/25070.].
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Nursing has been described as an art and a science. The scientific aspect of nursing can be learned in nursing school and in years of practice. However, the art of nursing is enriched by each nurse's connection with life experiences. The purpose of this article is to highlight my particular life experience with dance and to show how studying dance has helped me become the strong nursing leader I am today.
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BACKGROUND: Although shared decision-making (SDM) can better align patient preferences with treatment, barriers remain incompletely understood and the impact on patient satisfaction is unknown. METHODS: This is a qualitative study with semistructured interviews. A purposive sample of prevalent dialysis patients ≥65 years of age at two facilities in Greater Boston were selected for diversity in time from initiation, race, modality and vintage. A codebook was developed and interrater reliability was 89%. Codes were discussed and organized into themes. RESULTS: A total of 31 interviews with 23 in-center hemodialysis patients, 1 home hemodialysis patient and 7 peritoneal dialysis patients were completed. The mean age was 76 ± 9 years. Two dominant themes (with related subthemes) emerged: decision-making experiences and satisfaction, and barriers to SDM. Subthemes included negative versus positive decision-making experiences, struggling for autonomy, being a 'good patient' and lack of choice. In spite of believing that dialysis initiation should be the patient's choice, no patients perceived that they had made a choice. Patients explained that this is due to the perception of imminent death or that the decision to start dialysis belonged to physicians. Clinicians and family frequently overrode patient preferences, with patient autonomy honored mostly to select dialysis modality. Poor decision-making experiences were associated with low treatment satisfaction. CONCLUSIONS: Despite recommendations for SDM, many older patients were unaware that dialysis initiation was voluntary, held mistaken beliefs about their prognosis and were not engaged in decision-making, resulting in poor satisfaction. Patients desired greater information, specifically focusing on the acuity of their choice, prognosis and goals of care.
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Comportamento de Escolha , Tomada de Decisões , Satisfação do Paciente , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Percepção , Médicos , Pesquisa QualitativaRESUMO
OBJECTIVE: Neonatal ICUs and PICUs increasingly admit patients with chronic critical illness: children whose medical complexity leads to recurrent and prolonged ICU hospitalizations. We interviewed participants who routinely care for children with chronic critical illness to describe their experiences with ICU care for pediatric chronic critical illness. DESIGN: Semi-structured interviews. Interviews were transcribed and analyzed for themes. SETTING: Stakeholders came from five regions (Seattle, WA; Houston, TX; Jackson, MS; Baltimore, MD; and Philadelphia, PA). SUBJECTS: Fifty-one stakeholders including: 1) interdisciplinary providers (inpatient, outpatient, home care, foster care) with extensive chronic critical illness experience; or 2) parents of children with chronic critical illness. INTERVENTIONS: Telephone or in-person interviews. MEASUREMENTS AND MAIN RESULTS: Stakeholders identified several key issues and several themes emerged after qualitative analysis. Issues around chronic critical illness patient factors noted that patients are often relocated to the ICU because of their medical needs. During extended ICU stays, these children require longitudinal relationships and developmental stimulation that outstrip ICU capabilities. Family factors can affect care as prolonged ICU experience leads some to disengage from decision-making. Clinician factors noted that parents of children with chronic critical illness are often experts about their child's disease, shifting the typical ICU clinician-parent relationship. Comprehensive care for children with chronic critical illness can become secondary to needs of acutely ill patients. Lastly, with regard to system factors, stakeholders agreed that achieving consistent ICU care goals is difficult for chronic critical illness patients. CONCLUSIONS: ICU care is poorly adapted to pediatric chronic critical illness. Patient, family, clinician, and system factors highlight opportunities for targeted interventions toward improvement in care.
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Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Doença Crônica/terapia , Cuidados Críticos , Estado Terminal/terapia , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação , Criança , Continuidade da Assistência ao Paciente , Humanos , Entrevistas como Assunto , Pais/psicologia , Relações Profissional-Família , Relações Profissional-Paciente , Pesquisa Qualitativa , Estados UnidosRESUMO
Nursing has been described as an art and a science. The scientific aspect of nursing can be learned in nursing school and in years of practice. However, the art of nursing is enriched by each nurse's connection with life experiences. The purpose of this article is to highlight my particular life experience with dance and to show how studying dance has helped me become the strong nursing leader I am today.
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Atitude do Pessoal de Saúde , Dança , Empatia , Recursos Humanos de Enfermagem/psicologia , Competência Clínica , Humanos , Relações Enfermeiro-Paciente , Estados UnidosRESUMO
We examined the molecular basis of triazole resistance in Blumeria graminis f. sp. tritici (wheat mildew, Bgt), a model organism among powdery mildews. Four genetic models for responses to triazole fungicides were identified among US and UK isolates, involving multiple genetic mechanisms. Firstly, only two amino acid substitutions in CYP51B lanosterol demethylase, the target of triazoles, were associated with resistance, Y136F and S509T (homologous to Y137F and S524T in the reference fungus Zymoseptoria tritici). As sequence variation did not explain the wide range of resistance, we also investigated Cyp51B copy number and expression, the latter using both reverse transcription-quantitative PCR and RNA-seq. The second model for resistance involved higher copy number and expression in isolates with a resistance allele; thirdly, however, moderate resistance was associated with higher copy number of wild-type Cyp51B in some US isolates. A fourth mechanism was heteroallelism with multiple alleles of Cyp51B. UK isolates, with significantly higher mean resistance than their US counterparts, had higher mean copy number, a high frequency of the S509T substitution, which was absent from the United States, and in the most resistant isolates, heteroallelism involving both sensitivity residues Y136+S509 and resistance residues F136+T509. Some US isolates were heteroallelic for Y136+S509 and F136+S509, but this was not associated with higher resistance. The obligate biotrophy of Bgt may constrain the tertiary structure and thus the sequence of CYP51B, so other variation that increases resistance may have a selective advantage. We describe a process by which heteroallelism may be adaptive when Bgt is intermittently exposed to triazoles.
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Ascomicetos , Farmacorresistência Fúngica , Fungicidas Industriais , Dosagem de Genes , Farmacorresistência Fúngica/genética , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Fungicidas Industriais/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Triazóis/farmacologia , Doenças das Plantas/microbiologia , Triticum/microbiologia , Triticum/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Esterol 14-Desmetilase/genética , Esterol 14-Desmetilase/metabolismoRESUMO
Although children born preterm or low birth weight (PT LBW) are more likely to exhibit behavior problems compared to children born at term, developmental and family processes associated with these problems are unclear. We examined trajectories of maternal depressive symptoms in relation to toddler compliance and behavior problems in families with PT LBW infants. A total of 177 infants (93 boys, 84 girls) and their mothers enrolled in the study during the infant's NICU stay. Data were collected at five time points across 2 years. Assessments of maternal depressive symptoms were conducted at all time points, and toddler compliance and opposition to maternal requests and behavior problems were assessed at 2 years. Toddlers born earlier with more health problems to mothers whose depressive symptoms increased over time exhibited the most opposition to maternal requests during a cleanup task at 24 months, consistent with multiple risk models. Mothers with elevated depression symptoms reported more behavior problems in their toddlers. The study has implications for family-based early intervention programs seeking to identify PT LBW infants at highest risk for problem behaviors.
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The differential susceptibility to parenting model was examined in relation to toddler self-regulation in a prospective longitudinal study of infants born preterm or low birth weight. We followed 153 mother-infant dyads across five time points between the infant's Neonatal Intensive Care Unit stay and 24 months postterm. Assessments of infant temperament, quality of early parenting interactions, contextual variables, and toddler effortful control and behavior problems were conducted. Results supported differential susceptibility and dual risk models in addition to documenting main effects of early parenting on children's emerging self-regulation. Our data suggested that preterm or low birth weight infants who were prone to distress or rated by mothers as more difficult were particularly susceptible to the effects of early negative parenting.
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Desenvolvimento Infantil , Recém-Nascido de Baixo Peso/psicologia , Recém-Nascido Prematuro/psicologia , Poder Familiar/psicologia , Adolescente , Adulto , Transtornos do Comportamento Infantil/etiologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães/psicologia , Relações Pais-Filho , Estudos Prospectivos , Psicologia da Criança , Controles Informais da Sociedade , Fatores Socioeconômicos , Temperamento/fisiologia , Adulto JovemRESUMO
It is hypothesized that emotional arousal modulates long-term memory consolidation through the amygdala. Gaseous anesthetic agents are among the most potent drugs that cause temporary amnesia, yet the effects of inhalational anesthesia on human emotional memory processing remain unknown. To study this, two experiments were performed with the commonly used inhalational anesthetic sevoflurane. In experiment 1, volunteers responded to a series of emotional and neutral slides while under various subanesthetic doses of sevoflurane or placebo (no anesthesia). One week later, a mnemonic boost for emotionally arousing stimuli was evident in the placebo, 0.1%, and 0.2% sevoflurane groups, as measured with a recognition test. However, the mnemonic boost was absent in subjects who received 0.25% sevoflurane. Subsequently, in experiment 2, glucose PET assessed brain-state-related activity of subjects exposed to 0.25% sevoflurane. Structural equation modeling of the PET data revealed that 0.25% sevoflurane suppressed amygdala to hippocampal effective connectivity. The behavioral results show that 0.25% sevoflurane blocks emotional memory, and connectivity results demonstrate that this dose of sevoflurane suppresses the effective influence of the amygdala. Collectively, the findings support the hypothesis that the amygdala mediates memory modulation by demonstrating that suppressed amygdala effectiveness equates with a loss of emotional memory.
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Tonsila do Cerebelo/fisiologia , Anestésicos Inalatórios/farmacologia , Mapeamento Encefálico , Emoções/efeitos dos fármacos , Hipocampo/fisiologia , Memória/efeitos dos fármacos , Adolescente , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Éteres Metílicos/farmacologia , Tomografia por Emissão de Pósitrons , SevofluranoRESUMO
BACKGROUND: Community-based participatory approaches to research and intervention with ethnically and racially diverse minority groups demonstrate great promise to address health disparities. Refugees as a group have experienced a disproportionate amount of trauma, experience on-going resettlement and acculturative stressors, and have been shown to be at a heightened risk for psychological distress. OBJECTIVE: This article aims to extend current knowledge by examining best practices for use of community advisory boards (CABs) and youth advisory boards (YABs) to achieve mental health equity among refugee communities. METHODS: In order to improve outcomes in refugee communities, public health and mental health research and interventions should aim to engage refugees as active partners on advisory boards. Employing trauma-informed care principles through cultural humility, authentic engagement and power-sharing, recognition of the stigma of mental illness and mental health care, respect for community norms and preferences, and acknowledgement of acculturative and generational differences within refugee communities epitomize best practices in establishing and maintaining meaningful community advisory boards. CONCLUSIONS: Inclusion of trauma-informed CABs community adult and YABs in refugee mental health research and interventions ensures that the work is relevant and meaningful to those who are intended to benefit from these efforts.
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Refugiados , Aculturação , Adolescente , Adulto , Participação da Comunidade , Pesquisa Participativa Baseada na Comunidade , Humanos , Saúde MentalRESUMO
This prospective longitudinal study examined emerging effortful control skills at 24- and 36-months postterm in 172 children born preterm (<36 weeks gestation). Infant (neonatal health risks), family (sociodemographic risks), and maternal risk factors (depressive symptoms, anger expressions during play interactions) were assessed at six time points across 3 years. In addition, children's emerging effortful control skills, cognitive development, and mother-reported behavior and attention problems were assessed at 24 and 36 months. Analyses documented links between effortful control skills, cognitive skills, and concurrent attention problems in children born preterm. The study also found that preterm children's effortful control skills improved over time. In addition, neonatal health risks, family sociodemographic risks, and angry parenting interactions were associated with less optimal effortful control skills.
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Transtornos do Comportamento Infantil/psicologia , Comportamento Infantil/psicologia , Desenvolvimento Infantil/fisiologia , Recém-Nascido Prematuro/psicologia , Controles Informais da Sociedade , Análise de Variância , Transtornos do Comportamento Infantil/diagnóstico , Pré-Escolar , Emoções , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Relações Pais-Filho , Poder Familiar/psicologia , Fatores de Risco , Meio Social , Fatores SocioeconômicosRESUMO
Numerous methods exist for the pre-processing and analysis of skin-conductance response (SCR) data, but there is incomplete consensus on suitability and implementation, particularly with regard to signal filtering in conventional peak score (PS) analysis. This is particularly relevant when SCRs are measured during fMRI, which introduces additional noise and signal variability. Using SCR-fMRI data (n = 65 women) from a fear conditioning experiment, we compare the impact of three nested data processing methods on analysis using conventional PS as well as psychophysiological modeling. To evaluate the different methods, we quantify effect size to recover a benchmark contrast of interest, namely, discriminating SCR magnitude to a conditioned stimulus (CS+) relative to a CS not followed by reinforcement (CS-). Findings suggest that low-pass filtering reduces PS sensitivity (Δd = -20%), while band-pass filtering improves PS sensitivity (Δd = +27%). We also replicate previous findings that a psychophysiological modeling approach yields superior sensitivity to detect contrasts of interest than even the most sensitive PS method (Δd = +110%). Furthermore, we present preliminary evidence that filtering differences may account for a portion of exclusions made on commonly applied metrics, such as below zero discrimination. Despite some limitations of our sample and experimental design, it appears that SCR processing pipelines that include band-pass filtering, ideally with model-based SCR quantification, may increase the validity of SCR response measures, maximize research productivity, and decrease sampling bias by reducing data exclusion.
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Imageamento por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos , Condicionamento Clássico , Medo , Feminino , Resposta Galvânica da Pele , HumanosRESUMO
This study tested whether L-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg L-DOPA/carbidopa (n = 28), or 200/50 mg L-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of L-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that L-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.
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Transtornos de Estresse Pós-Traumáticos , Adulto , Condicionamento Clássico , Extinção Psicológica , Medo , Feminino , Humanos , Levodopa , Imageamento por Ressonância Magnética , Rememoração Mental , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológicoRESUMO
BACKGROUND: The ADHD Self Report Scale is a self-report measure that assesses attentional problems. We sought to validate the ASRS by establishing neural correlates using functional magnetic imaging in healthy controls and individuals with bipolar disorder (BD), who commonly exhibit attentional problems. METHODS: ASRS questionnaires and functional MRI data in conjunction with the Multi-source Interference Task (MSIT) were collected from 36 healthy control and 36 BD participants. We investigated task specific changes in the dorsal anterior cingulate cortex (dACC, Brodmann area 32) and their correlations with ASRS subscale scores, inattention and hyperactivity, in both cohorts. RESULTS: As hypothesized, the dACC showed significant increases in BOLD activation between the interference and noninterference conditions. For the ASRS scale as well as its Inattention and Hyperactivity subscales, there was a significant negative correlation with the dACC BOLD for the whole group. CONCLUSIONS: The ASRS is sensitive to attentional difficulties in BD, suggesting that it is a valid tool for assessing attentional difficulties in patients with BD.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Bipolar , Autorrelato , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Inquéritos e QuestionáriosRESUMO
Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC structures have shown promise for treating both OCD and related disorders involving over-expression of automatic/habitual behaviors. Physiologically, we propose that this CSTC hyper-connectivity may be reflected in high synchrony of neural firing between loop structures, which could be measured as coherent oscillations in the local field potential (LFP). Here we report the results from the pilot patient in an Early Feasibility study (https://clinicaltrials.gov/ct2/show/NCT03184454) in which we use the Medtronic Activa PC+ S device to simultaneously record and stimulate in the supplementary motor area (SMA) and ventral capsule/ventral striatum (VC/VS). We hypothesized that frequency-mismatched stimulation should disrupt coherence and reduce compulsive symptoms. The patient reported subjective improvement in OCD symptoms and showed evidence of improved cognitive control with the addition of cortical stimulation, but these changes were not reflected in primary rating scales specific to OCD and depression, or during blinded cortical stimulation. This subjective improvement was correlated with increased SMA and VC/VS coherence in the alpha, beta, and gamma bands, signals which persisted after correcting for stimulation artifacts. We discuss the implications of this research, and propose future directions for research in network modulation in OCD and more broadly across psychiatric disorders.
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OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.
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Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Testosterona/uso terapêutico , Adulto , Idoso , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Humanos , Hidrocortisona/sangue , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Creme para a Pele , Testosterona/administração & dosagem , Testosterona/sangue , Adulto JovemRESUMO
BACKGROUND: The Drosophila Shaker mutant fruit-fly, with its malfunctioning voltage-gated potassium channel, exhibits anesthetic requirements that are more than twice normal. Shaker mutants with an abnormal Kv1.2 channel also demonstrate significantly reduced sleep. Given the important role the thalamus plays in both sleep and arousal, the authors investigated whether localized central medial thalamic (CMT) microinfusion of an antibody designed to block the pore of the Kv1.2 channel might awaken anesthetized rats. METHODS: Male Sprague-Dawley rats were implanted with a cannula aimed at the CMT or lateral thalamus. One week later, unconsciousness was induced with either desflurane (3.6 +/- 0.2%; n = 55) or sevoflurane (1.2 +/- 0.1%; n = 51). Arousal effects of a single 0.5-microl infusion of Kv1.2 potassium channel blocking antibody (0.1- 0.2 mg/ml) or a control infusion of Arc-protein antibody (0.2 mg/ml) were then determined. RESULTS: The Kv1.2 antibody, but not the control antibody, temporarily restored consciousness in 17% of all animals and in 75% of those animals where infusions occurred within the CMT (P < 0.01 for each anesthetic). Lateral thalamic infusions showed no effects. Consciousness returned on average (+/- SD) 170 +/- 99 s after infusion and lasted a median time of 398 s (interquartile range: 279-510 s). Temporary seizures, without apparent consciousness, predominated in 33% of all animals. CONCLUSIONS: These findings support the idea that the CMT plays a role in modulating levels of arousal during anesthesia and further suggest that voltage-gated potassium channels in the CMT may contribute to regulating arousal or may even be relevant targets of anesthetic action.
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Anestesia por Inalação , Nível de Alerta/fisiologia , Estado de Consciência , Canal de Potássio Kv1.2/metabolismo , Canais de Potássio/efeitos dos fármacos , Núcleos Talâmicos/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Animais , Anticorpos/metabolismo , Estado de Consciência/efeitos dos fármacos , Estado de Consciência/fisiologia , Proteínas do Citoesqueleto , Desflurano , Drosophila , Isoflurano/administração & dosagem , Isoflurano/análogos & derivados , Masculino , Éteres Metílicos/administração & dosagem , Microinjeções/métodos , Proteínas do Tecido Nervoso , Canais de Potássio/imunologia , Canais de Potássio/fisiologia , Ratos , Ratos Sprague-Dawley , Sevoflurano , Núcleos Talâmicos/anatomia & histologia , Núcleos Talâmicos/metabolismoRESUMO
Purpose: Between 2000 and 2012, the incident dialysis population in the United States increased by nearly 60%, most sharply among adults 75 years and older. End-of-life (EOL) conversations among dialysis patients are associated with better patient-centered outcomes and lower use of aggressive interventions in the last month of life. This study examined how health literacy may affect engagement, comprehension, and satisfaction with EOL conversations among elderly dialysis patients. Design and Methods: Qualitative/descriptive study with semi-structured interviews about health literacy, EOL conversations, and goals of care with 31 elderly dialysis patients at 2 centers in Boston. Themes were interpreted in the context of Nutbeam's health literacy framework. Results: Despite high mortality risk in this population, only 13% of patients had discussed EOL preferences with physicians, half had discussed EOL with their social network, and 25% of participants explicitly stated that they had never considered EOL preferences. Less than 30% of participants could correctly define terminology commonly used in EOL conversations. Analyses yielded 5 themes: (1) Misunderstanding EOL terminology; (2) Nephrologists reluctant to discuss EOL; (3) Patients conforming to socially constructed roles; (4) Discordant expectations and dialysis experiences; and (5) Reconciling EOL values and future care. Patients had limited understanding of EOL terminology, lacked of opportunities for meaningful EOL discussion with providers and family, resulting in uncertainty about future care. Implications: Limited health literacy presents a substantial barrier to communication and could lead to older adults committing to an intensive pattern of care without adequate information. Clinicians should consider health literacy when discussing dialysis initiation.