A randomized, placebo-controlled, double-blinded mechanistic clinical trial using endotoxin to evaluate the relationship between insomnia, inflammation, and affective disturbance on pain in older adults: A protocol for the sleep and Healthy Aging Research for pain (SHARE-P) study.

Chronic pain is prevalent in older adults. Treatment, especially with opioids, is often ineffective and poses considerable negative consequences in this population. To improve treatment, it is important to understand why older adults are at a heightened risk for developing chronic pain. Insomnia is a major modifiable risk factor for chronic pain that is ubiquitous among older adults. Insomnia can also lead to heightened systemic inflammation and affective disturbance, both of which may further exacerbate pain conditions in older adults. Endotoxin exposure can be used as an experimental model of systemic inflammation and affective disturbance. The current study aims to understand how insomnia status and endotoxin-induced changes in inflammation and affect (increased negative affect and decreased positive affect) may interact to impact pain facilitatory and inhibitory processes in older adults. Longitudinal data will also assess how pain processing, affective, and inflammatory responses to endotoxin may predict the development of pain and/or depressive symptoms. The current study is a randomized, double-blinded, placebo-controlled, mechanistic clinical trial in men and women, with and without insomnia, aged 50 years and older. Participants were randomized to either 0.8ng/kg endotoxin injection or saline placebo injection. Daily diaries were used to collect variables related to sleep, mood, and pain at two-week intervals during baseline and 3-, 6-, 9-, and 12-months post-injection. Primary outcomes during the experimental phase include conditioned pain modulation, temporal summation, and affective pain modulation ∼5.5 hours after injection. Primary outcomes for longitudinal assessments are self-reported pain intensity and depressive symptoms. The current study uses endotoxin as an experimental model for pain. In doing so, it aims to extend the current literature by: (1) including older adults, (2) investigating insomnia as a potential risk factor for chronic pain, (3) evaluating the role of endotoxin-induced affective disturbances on pain sensitivity, and (4) assessing sex differences in endotoxin-induced hyperalgesia. Clinicaltrialsgov: NCT03256760. Trial sponsor: NIH R01AG057750-01.

Sleep and Healthy Aging Research on Depression (SHARE-D) randomized controlled trial: Protocol overview of an experimental model of depression with insomnia, inflammation, and affect mechanisms in older adults.

Depression, one of the most common diseases in older adults, carries significant risk for morbidity and mortality. Because of the burgeoning population of older adults, the enormous burden of late-life depression, and the limited efficacy of current antidepressants in older adults, biologically plausible models that translate into selective depression prevention strategies are needed. Insomnia predicts depression recurrence and is a modifiable target to prevent incident and recurrent depression in older adults. Yet, it is not known how insomnia gets converted into biological- and affective risk for depression, which is critical for identification of molecular targets for pharmacologic interventions, and for refinement of insomnia treatments that target affective responding to improve efficacy. Sleep disturbance activates inflammatory signaling and primes immune responses to subsequent inflammatory challenge. In turn, inflammatory challenge induces depressive symptoms, which correlate with activation of brain regions implicated in depression. This study hypothesizes that insomnia serves as a vulnerability factor for inflammation-related depression; older adults with insomnia will show heightened inflammatory- and affective responding to inflammatory challenge as compared to those without insomnia. To test this hypothesis, this protocol paper describes a placebo-controlled, randomized, double-blind study of low dose endotoxin in older adults (n = 160; 60-80 y) with insomnia vs. comparison controls without insomnia. The aims of this study are to examine differences in depressive symptoms, measures of negative affective responding, and measures of positive affective responding as a function of insomnia and inflammatory challenge. If the hypotheses are confirmed, older adults with two "hits", insomnia and inflammatory activation, would represent a high risk group to be prioritized for monitoring and for depression prevention efforts using treatments that target insomnia or inflammation. Moreover, this study will inform the development of mechanism-based treatments that target affect responses in addition to sleep behaviors, and which might also be coupled with efforts to reduce inflammation to optimize efficacy of depression prevention.

Costs associated with treatment of insomnia in Alzheimer's disease caregivers: a comparison of mindfulness meditation and cognitive behavioral therapy for insomnia.

BACKGROUND: Among the over 5 million informal caregivers for patients with Alzheimer's disease (AD) in the United States (US), over 60% experience insomnia. Research on insomnia treatment efficacy in AD caregivers is limited. An ongoing randomized non-inferiority clinical trial, the Caregiver Sleep Research study, is evaluating whether mindfulness meditation is non-inferior to cognitive behavioral therapy for insomnia (CBT-I) in the treatment of insomnia in AD caregivers. The present report examines estimated intervention costs in this ongoing trial. METHODS: Micro-costing was used to itemize and abstract costs of the two interventions: a mindfulness-based intervention known as mindful awareness practices for insomnia (MAP-I); and CBT-I. This approach involves collecting detailed data on resources utilized and the unit costs of those resources, thereby revealing actual resource use and economic costs for each treatment arm. Personnel time, patient time, and supplies were inventoried, and unit costs were applied. Caregiver time costs, including travel, were based on US Labor Bureau home-health aide national mean hourly wages; instructor/staff costs were based on hourly wages. Per-participant and program costs were calculated assuming individual- and group-delivery to reflect real-world implementation. Sensitivity analyses evaluated robustness of estimates. RESULTS: From the societal perspective, per-participant MAP-I costs were $1884 for individual and $1377 for group delivery; for CBT-I, these costs were $3978 and $1981, respectively. Compared with CBT-I, MAP-I provided cost savings of $2094 (53%) and $604 (30%) per treated caregiver for individual and group delivery, respectively. From the US healthcare system perspective, MAP-I vs. CBT-I participant savings were $1872 (65%) for individual and $382 (44%) for group interventions, respectively. For MAP-I and CBT-I, instructor in-class time was the highest cost component. Results were most sensitive to combined instructor time costs. CONCLUSIONS: Treatment of insomnia with MAP-I, compared to CBT-I, yields substantial cost savings for society and the healthcare system. With this potential for cost savings, results of the ongoing non-inferiority trial have critical implications for insomnia treatment dissemination and its benefits to AD caregivers and other community populations with insomnia.

Marcadores de estrés oxidativo en embarazadas diabéticas / Markers of oxidative stress in diabetic pregnants

Introducción: El manejo del estrés oxidativo en la embarazada diabética podría ser beneficioso en la prevención de complicaciones como las malformaciones congénitas. Sin embargo, no existe un consenso en cuanto a la pertinencia de aplicar terapias antioxidantes previamente o durante la gestación. La ambigüedad de algunos resultados en cuanto al daño real sobre las biomoléculas pudiera ser la causa de tal desacuerdo. El estudio tuvo como objetivos evaluar el estado de marcadores de daño oxidativo a biomoléculas y de defensa antioxidante en embarazadas diabéticas, así como analizar la influencia del tipo diabetes en el estado REDOX durante la gestación. Métodos: Se estudiaron 32 embarazadas diabéticas (15 con diabetes pregestacional y 17 gestacional) y 27 sanas, con un tiempo de gestación promedio superior a 20 semanas. Los marcadores se evaluaron por técnicas espectrofotométricas y cromatografía líquida de alta presión. Resultados: se pudo asegurar daño oxidativo al material genético y a proteínas, unido a una disminución también significativa de las defensas antioxidantes mediadas por el glutatión reducido en las embarazadas con diabetes pregestacional. Los niveles de nitratos y nitritos no mostraron diferencias entre los grupos. Conclusiones: los resultados permiten asegurar una vez más que las mujeres con diabetes pregestacional presentan un estado de estrés oxidativo que deteriora las defensas antioxidantes y no logra contrarrestar el daño oxidativo a biomoléculas

Introduction: The management of oxidative stress in diabetic pregnants could be beneficial to prevent complications like the congenital malformations. However, there is not a consensus as regards the relevance of applying antioxidant therapies before or during pregnancy. The ambiguity of some results as regard the real damage on biomolecules could be the cause of such disagreement. The aims of present study were to assess the state of the markers of oxidative damage to biomolecules and the antioxidant defence in diabetic pregnants, as well as to analyze the influence of the type of diabetes on the REDOX state during pregnancy. Methods: Thirty two diabetic pregnants (15 with pregestational diabetes and 17 with gestational diabetes) and 27 healthy pregnants with an average pregnant time higher than 20 weeks. Markers were assessed using spectrophotometry and high-performance liquid chromatography techniques. Results: There was oxidative damage to genetic material and proteins together with a decrease also significant in antioxidant defenses mediated by the reduced glutathione in pregestational diabetic pregnants. The nitrates and nitrites levels were not different among groups. Conclusions: Results allowed us to make sure that women with pregestional diabetes had a oxidative stress state deteriorating the antioxidant defenses and not counteract the oxidative damage to biomolecules

Marcadores de estrés oxidativo en embarazadas diabéticas / Markers of oxidative stress in diabetic pregnants

Introducción: El manejo del estrés oxidativo en la embarazada diabética podría ser beneficioso en la prevención de complicaciones como las malformaciones congénitas. Sin embargo, no existe un consenso en cuanto a la pertinencia de aplicar terapias antioxidantes previamente o durante la gestación. La ambigüedad de algunos resultados en cuanto al daño real sobre las biomoléculas pudiera ser la causa de tal desacuerdo. El estudio tuvo como objetivos evaluar el estado de marcadores de daño oxidativo a biomoléculas y de defensa antioxidante en embarazadas diabéticas, así como analizar la influencia del tipo diabetes en el estado REDOX durante la gestación. Métodos: Se estudiaron 32 embarazadas diabéticas (15 con diabetes pregestacional y 17 gestacional) y 27 sanas, con un tiempo de gestación promedio superior a 20 semanas. Los marcadores se evaluaron por técnicas espectrofotométricas y cromatografía líquida de alta presión. Resultados: se pudo asegurar daño oxidativo al material genético y a proteínas, unido a una disminución también significativa de las defensas antioxidantes mediadas por el glutatión reducido en las embarazadas con diabetes pregestacional. Los niveles de nitratos y nitritos no mostraron diferencias entre los grupos. Conclusiones: los resultados permiten asegurar una vez más que las mujeres con diabetes pregestacional presentan un estado de estrés oxidativo que deteriora las defensas antioxidantes y no logra contrarrestar el daño oxidativo a biomoléculas(AU)

Introduction: The management of oxidative stress in diabetic pregnants could be beneficial to prevent complications like the congenital malformations. However, there is not a consensus as regards the relevance of applying antioxidant therapies before or during pregnancy. The ambiguity of some results as regard the real damage on biomolecules could be the cause of such disagreement. The aims of present study were to assess the state of the markers of oxidative damage to biomolecules and the antioxidant defence in diabetic pregnants, as well as to analyze the influence of the type of diabetes on the REDOX state during pregnancy. Methods: Thirty two diabetic pregnants (15 with pregestational diabetes and 17 with gestational diabetes) and 27 healthy pregnants with an average pregnant time higher than 20 weeks. Markers were assessed using spectrophotometry and high-performance liquid chromatography techniques. Results: There was oxidative damage to genetic material and proteins together with a decrease also significant in antioxidant defenses mediated by the reduced glutathione in pregestational diabetic pregnants. The nitrates and nitrites levels were not different among groups. Conclusions: Results allowed us to make sure that women with pregestional diabetes had a oxidative stress state deteriorating the antioxidant defenses and not counteract the oxidative damage to biomolecules(AU)

The importance of botellas and other plant mixtures in Dominican traditional medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant mixtures are understudied in ethnobotanical research. AIM OF THE STUDY: To investigate the importance of plant mixtures (remedies consisting of at least two plants) in Dominican traditional medicine. MATERIALS AND METHODS: A Spanish language questionnaire was administered to 174 Dominicans living in New York City (NYC) and 145 Dominicans living in the Dominican Republic (DR), including lay persons (who self-medicate with plants) and specialists (traditional healers). Plants were identified through specimens purchased in NYC botánica shops and Latino grocery shops, and from voucher collections. RESULTS: The percentage of mixtures as compared to single plants in plant use reports varied between 32 and 41%, depending on the geographic location (NYC or DR) and participant status (lay person or specialist). Respiratory conditions, reproductive health and genitourinary conditions were the main categories for which Dominicans use plant mixtures. Lay persons reported significantly more mixtures prepared as teas, mainly used in NYC to treat respiratory conditions. Specialists mentioned significantly more botellas (bottled herbal mixtures), used most frequently in the DR to treat reproductive health and genitourinary conditions. Cluster analysis demonstrated that different plant species are used to treat respiratory conditions as compared to reproductive health and genitourinary conditions. Interview participants believed that combining plants in mixtures increases their potency and versatility as medicines. CONCLUSIONS: The present study demonstrates the importance and complexity of plant mixtures in Dominican traditional medicine and the variation in its practices influenced by migration from the DR to NYC, shedding new light on the foundations of a particular ethnomedical system.

Disminución de la capacidad antioxidante en niños y adolescentes diabéticos / Reduction of the antioxidant capacity in diabetic children and adolescents

Se propuso demostrar que la diabetes en niños y adolescentes evoluciona con incremento de especies reactivas, las cuales circulan al nivel sistémico y pueden dañar las biomoléculas. Se evidenció que los niños diabéticos tienen disminuidas las defensas antioxidantes, presumiblemente por causa de su mayor utilización. A pesar de observarse una tendencia a su incremento, no resultó significativa la diferencia en los niveles de daño a proteínas, aunque sí el daño a lípidos entre los pacientes diabéticos y el grupo de niños control. El análisis de los valores obtenidos permitirá la elaboración de una estrategia terapéutica, que comprenda la indicación de antioxidantes específicos en los pacientes que así lo requieran.

The aim of this study was to prove that diabetes in children and adolescents evolves with an increment of reactive species circulating at the systemic level and that may lead to biomolecular damage. It was evidenced that the diabetic children have the antioxidant defenses reduced due maybe to their greater utilization. In spite of the fact that a tendency to their increase was observed, the difference at the levels of protein damage was not significant, although the lipid damage among the diabetic patients and the control group of children was marked. The analysis of the values obtained will allow to lay down a therapeutic strategy including the indication of specific antioxidants in those patients requiring them.

Disminución de la capacidad antioxidante en niños y adolescentes diabético / Reduction of the antioxidant capacity in diabetic children and adolescents

Se propuso demostrar que la diabetes en niños y adolescentes evoluciona con incremento de especies reactivas, las cuales circulan al nivel sistémico y pueden dañar las biomoléculas. Se evidenció que los niños diabéticos tienen disminuidas las defensas antioxidantes, presumiblemente por causa de su mayor utilización. A pesar de observarse una tendencia a su incremento, no resultó significativa la diferencia en los niveles de daño a proteínas, aunque sí el daño a lípidos entre los pacientes diabéticos y el grupo de niños control. El análisis de los valores obtenidos permitirá la elaboración de una estrategia terapéutica, que comprenda la indicación de antioxidantes específicos en los pacientes que así lo requieran(AU)