Mindfulness skills and experiential avoidance as therapeutic mechanisms for treatment-resistant depression through mindfulness-based cognitive therapy and lifestyle modification.

Background/objective: The COVID-19 pandemic and consequent physical distancing has made it difficult to provide care for those with Treatment-Resistant Depression (TRD). As a secondary analysis of a clinical trial, the aim of this study was to explore potential mechanisms through which three online-delivered approaches, added to treatment as usual, improve depressive symptoms in TRD patients. Methods: The three approaches included (a) Minimal Lifestyle Intervention (MLI), (b) Mindfulness-Based Cognitive Therapy (MBCT), and (c) Lifestyle Modification Program (LMP). Sixty-six participants with TRD completed assessments pre-post intervention (mindfulness skills [FFMQ]; self-compassion [SCS]; and experiential avoidance [AAQ-II]) and pre-intervention to follow-up (depressive symptoms [BDI-II]). Data were analyzed using within-subjects regression models to test mediation. Results: Mindfulness skills mediated the effect of MBCT on depressive symptoms (ab = -4.69, 95% CI = -12.93 to-0.32), whereas the lack of experiential avoidance mediated the effect of LMP on depressive symptoms (ab = -3.22, 95% CI = -7.03 to-0.14). Conclusion: Strengthening mindfulness skills and decreasing experiential avoidance may promote recovery in patients with TRD, MBCT, and LMP have demonstrated that they may help increase mindfulness skills and decrease experiential avoidance, respectively. Future work will need to unpick the components of these interventions to help isolate active ingredients and increase optimization.

Efficacy of an adjuvant non-face-to-face multimodal lifestyle modification program for patients with treatment-resistant major depression: A randomized controlled trial.

BACKGROUND: The high prevalence of depression is partly attributable to the poor response of patients to first-line antidepressants. Multimodal programs that promote a healthy lifestyle are successful in treating depression when used as a complementary therapy, but their medium- and long-term benefits have not been demonstrated for patients with treatment-resistant depression (TRD). The main aim of this study was to compare the effectiveness of a lifestyle modification program (LMP) with mindfulness-based cognitive therapy (MBCT) and a placebo-control (written suggestions for lifestyle changes) in Spanish patients with TRD. METHODS: This controlled clinical trial randomized 94 patients with TRD into 3 arms. The primary outcome was the Beck Depression Inventory-II (BDI-II) score at baseline, 2, 6 and 12 months. The secondary outcomes were changes in scores that evaluated quality-of-life, adherence to the Mediterranean diet, physical activity, and social support. RESULTS: Relative to the placebo group, the LMP and MBCT groups had significantly better quality of life (p = 0.017; p = 0.027), and the LMP group had significantly better adherence to the Mediterranean diet (p<0.001) and reduced use of antidepressants (p = 0.036). However, the three groups showed no significant differences in BDI-II score. LIMITATIONS: Only about half of the planned 180 patients were recruited, in part due to the COVID-19 pandemic. CONCLUSIONS: There was no evidence that the LMP treatment significantly reduced symptoms of depression relative to the other groups during the COVID-19 lockdown.

Guía práctica de seguimiento y manejo del paciente con asma grave tratado con biológicos / Practical guide for the follow-up and management of patients with severe asthma treated with biologics

El manejo del asma grave descontrolada con biológicos es un área de extrema dificultad, dada la escasez de información respecto a los criterios de inicio de los mismos, las variables a evaluar para determinar la eficacia y seguridad de su manejo, los puntos de corte para determinar el momento oportuno para cambiar o agregar otro biológico y el proceso para disminuir o retirar los esteroides. Esta revisión incorpora la información más reciente y realiza una propuesta con base en ella.

The management of severe uncontrolled asthma with biologics is an area of extreme difficulty given the scarcity of information regarding their starting criteria, the variables to be evaluated to determine the efficacy and safety of their management, the cut-off points to determine the timing to change or add another biological and the process to decrease or withdraw steroids. This review incorporates the latest information and makes a proposal based on it

Effectiveness of a healthy lifestyle promotion program as adjunctive teletherapy for treatment-resistant major depression during COVID 19 pandemic: A randomized clinical trial protocol.

INTRODUCTION: Treatment-resistant depression (TRD) has a high prevalence and can be exacerbated by poor physical health and economic hardships, which have become common stressors during the current COVID-19 pandemic. The therapeutic approaches used to treat these patients are not always available, may be not be accepted by some patients, and often require face-to-face interactions. OBJECTIVE: The main aim of this study will be to evaluate the effectiveness of an Internet-based adjuvant lifestyle-based intervention for patients with TRD. METHODS: This will be a parallel, randomized, and controlled clinical trial. A total of 180 patients with TRD will be randomly allocated (1:1:1) to 1 of 3 groups: treatment prescribed by the mental health team and written suggestions for lifestyle changes (placebo control group); treatment prescribed by the mental health team, written suggestions for lifestyle changes, and an 8-week mindfulness-based cognitive therapy program (active control group); or treatment prescribed by the mental health team, written suggestions for lifestyle changes, and an 8-week lifestyle change promotion program (intervention group). We will perform this study during the COVID-19 pandemic, and will administer interventions by teletherapy, and contact participants by telephone calls, text messages, and/or teleconferences. We will collect patient data using questionnaires administered at baseline, immediately after the intervention, and after 6 and 12 months. The primary outcome will be score on the Beck Depression Inventory-II. The secondary outcomes will be score on the Clinical Global Impressions Scale (used to quantify and track patient progress and treatment response over time) and health-related quality of life measured using the European Quality of Life-5 Dimensions Questionnaire. DISCUSSION: Patients with TRD are especially vulnerable when face-to-face psychotherapy is unavailable. The main strength of the proposed study is the novelty of the intervention to be used as an adjuvant therapy. Our results may provide guidance for treatment of patients with TRD in future situations that require lockdown measures. CLINICALTRIALS REGISTRATION NUMBER: NCT04428099.

Modified CDKN2B (p15) and CDKN2A (p16) DNA methylation profiles in urban pesticide applicators.

Gene-specific changes in DNA methylation by pesticides in occupationally exposed populations have not been studied extensively. Of particular concern are changes in the methylation profile of tumor-suppressor, such as CDKN2B and CDKN2A, genes involved in oncogenesis. The aim of this study was to evaluate the methylation profiles of CDKN2B and CDKN2A genes in urban pesticide applicators and their relationship with occupational exposure to pesticides. A cross-sectional study was conducted in 186 urban pesticide applicators (categorized as high or moderate exposures) and 102 participants without documented occupational exposures to pesticides. Acute and chronic pesticide exposures were evaluated by direct measurement of urinary dialkylphosphates, organophosphate metabolites, and a structured questionnaire, respectively. Anthropometric characteristics, diet, clinical histories, and other variables were estimated through a validated self-reported survey. DNA methylation was determined by pyrosequencing of bisulfite-treated DNA. Decreased DNA methylation of the CDKN2B gene was observed in pesticide-exposed groups compared to the non-exposed group. In addition, increased methylation of the CDKN2A promoter was observed in the moderate-exposure group compared to the non-exposed group. Bivariate analysis showed an association between CDKN2B methylation and pesticide exposure, general characteristics, smoking status, and micronutrients, while changes in CDKN2A methylation were associated with pesticide exposure, sex, educational level, body mass index, smoking status, supplement intake, clinical parameters, and caffeine consumption. These data suggest that pesticide exposure modifies the methylation pattern of CDKN2B and CDKN2A genes and raise important questions about the role that these changes may play in the regulation of cell cycle activities, senescence, and aging.

S-Allylcysteine, a garlic-derived antioxidant, ameliorates quinolinic acid-induced neurotoxicity and oxidative damage in rats.

Excitotoxicity elicited by overactivation of N-methyl-D-aspartate receptors is a well-known characteristic of quinolinic acid-induced neurotoxicity. However, since many experimental evidences suggest that the actions of quinolinic acid also involve reactive oxygen species formation and oxidative stress as major features of its pattern of toxicity, the use of antioxidants as experimental tools against the deleterious effects evoked by this neurotoxin becomes more relevant. In this work, we investigated the effect of a garlic-derived compound and well-characterized free radical scavenger, S-allylcysteine, on quinolinic acid-induced striatal neurotoxicity and oxidative damage. For this purpose, rats were administered S-allylcysteine (150, 300 or 450 mg/kg, i.p.) 30 min before a single striatal infusion of 1 microl of quinolinic acid (240 nmol). The lower dose (150 mg/kg) of S-allylcysteine resulted effective to prevent only the quinolinate-induced lipid peroxidation (P < 0.05), whereas the systemic administration of 300 mg/kg of this compound to rats decreased effectively the quinolinic acid-induced oxidative injury measured as striatal reactive oxygen species formation (P < 0.01) and lipid peroxidation (P < 0.05). S-Allylcysteine (300 mg/kg) also prevented the striatal decrease of copper/zinc-superoxide dismutase activity (P < 0.05) produced by quinolinate. In addition, S-allylcysteine, at the same dose tested, was able to reduce the quinolinic acid-induced neurotoxicity evaluated as circling behavior (P < 0.01) and striatal morphologic alterations. In summary, S-allylcysteine ameliorates the in vivo quinolinate striatal toxicity by a mechanism related to its ability to: (a) scavenge free radicals; (b) decrease oxidative stress; and (c) preserve the striatal activity of Cu,Zn-superoxide dismutase (Cu,Zn-SOD). This antioxidant effect seems to be responsible for the preservation of the morphological and functional integrity of the striatum.