Comparative Effectiveness of Psychotherapy vs Antidepressants for Depression in Heart Failure: A Randomized Clinical Trial.

Importance: Heart failure (HF) affects more than 6 million adults in the US and more than 64 million adults worldwide, with 50% prevalence of depression. Patients and clinicians lack information on which interventions are more effective for depression in HF. Objective: To compare the effectiveness of behavioral activation psychotherapy (BA) vs antidepressant medication management (MEDS) on patient-centered outcomes inpatients with HF and depression. Design, Setting, and Participants: This pragmatic randomized comparative effectiveness trial was conducted from 2018 to 2022, including 1-year follow-up, at a not-for-profit academic health system serving more than 2 million people from diverse demographic, socioeconomic, cultural, and geographic backgrounds. Participant included inpatients and outpatients diagnosed with HF and depression, and data were analyzed as intention-to-treat. Data were analyzed from 2022 to 2023. Interventions: BA is an evidence-based manualized treatment for depression, promoting engagement in personalized pleasurable activities selected by patients. MEDS involves the use of an evidence-based collaborative care model with care managers providing coordination with patients, psychiatrists, and primary care physicians to only administer medications. Main Outcomes and Measures: The primary outcome was depressive symptom severity at 6 months, measured using the Patient Health Questionnaire 9-Item (PHQ-9). Secondary outcomes included physical and mental health-related quality of life (HRQOL), measured using the Short-Form 12-Item version 2 (SF-12); heart failure-specific HRQOL, measured using the Kansas City Cardiomyopathy Questionnaire; caregiver burden, measured with the Caregiver Burden Questionnaire for Heart Failure; emergency department visits; readmissions; days hospitalized; and mortality at 3, 6, and 12 months. Results: A total of 416 patients (mean [SD] age, 60.71 [15.61] years; 243 [58.41%] male) were enrolled, with 208 patients randomized to BA and 208 patients randomized to MEDS. At baseline, mean (SD) PHQ-9 scores were 14.54 (3.45) in the BA group and 14.31 (3.60) in the MEDS group; both BA and MEDS recipients experienced nearly 50% reduction in depressive symptoms at 3, 6, and 12 months (eg, mean [SD] score at 12 months: BA, 7.62 (5.73); P < .001; MEDS, 7.98 (6.06); P < .001; between-group P = .55). There was no statistically significant difference between BA and MEDS in the primary outcome of PHQ-9 at 6 months (mean [SD] score, 7.53 [5.74] vs 8.09 [6.06]; P = .88). BA recipients, compared with MEDS recipients, experienced small improvement in physical HRQOL at 6 months (mean [SD] SF-12 physical score: 38.82 [11.09] vs 37.12 [10.99]; P = .04), had fewer ED visits (3 months: 38% [95% CI, 14%-55%] reduction; P = .005; 6 months: 30% [95% CI, 14%-40%] reduction; P = .008; 12 months: 27% [95% CI, 15%-38%] reduction; P = .001), and spent fewer days hospitalized (3 months: 17% [95% CI, 8%-25%] reduction; P = .002; 6 months: 19% [95% CI, 13%-25%] reduction; P = .005; 12 months: 36% [95% CI, 32%-40%] reduction; P = .001). Conclusions and Relevance: In this comparative effectiveness trial of BA and MEDS in patients with HF experiencing depression, both treatments significantly reduced depressive symptoms by nearly 50% with no statistically significant differences between treatments. BA recipients experienced better physical HRQOL, fewer ED visits, and fewer days hospitalized. The study findings suggested that patients with HF could be given the choice between BA or MEDS to ameliorate depression. Trial Registration: ClinicalTrials.gov Identifier: NCT03688100.

The Impact of Psilocybin on Patients Experiencing Psychiatric Symptoms: A Systematic Review of Randomized Clinical Trials.

Objective: This systematic review aims to evaluate the impact of psilocybin on patients experiencing psychiatric symptoms, with a focus on health-related quality of life (HRQoL) and safety. Method of Research: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed database and identified studies published from January 2011 to December 2021 pertaining to the impact of psilocybin on psychiatric symptoms. Two authors independently conducted a focused analysis and reached a final consensus on five studies meeting the specific selection criteria. Study bias was addressed using the Cochrane risk of bias tool. Results: The impact of psilocybin on psychiatric symptoms was examined in five randomized controlled trials (RCTs). Four studies administered 1 to 2 doses of psilocybin, with doses ranging from 14mg/70kg to 30mg/70kg, and one study administered a fixed dose of 25mg to all participants. Administration of psilocybin resulted in significant and sustained reduction in symptoms of anxiety and depression, enhanced sense of wellbeing, life satisfaction, and positive mood immediately after psilocybin administration and up to six months after conclusion of treatment. All studies included some form of psychotherapy, and none reported serious adverse effects. Conclusion: RCTs show the efficacy of psilocybin in the treatment of anxiety and depression symptoms, as well as improvement in HRQoL, and no serious side effects. However, additional research is necessary to characterize predictors of treatment response, patient screening requirements, effectiveness in broader clinical populations, and guidelines for psilocybin-assisted psychotherapy.

Surgical Interventions for Lumbosacral Plexus Injuries: A Systematic Review.

Background: Nerve reconstruction techniques for lumbosacral plexus (LSP) injuries vary. There are no clear treatment guidelines available, and summative evaluations of the literature discussing these surgeries are lacking. For these reasons, this investigation aimed to systematically review and consolidate all available literature discussing surgical interventions for LSP injuries and cohesively present patient-reported and objective postoperative outcomes. Methods: The authors conducted a systematic review using PubMed, Embase, Web of Science, ProQuest Dissertations and Theses Global (via Proquest.com), and ClinicalTrials.gov databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After title and abstract screening, identified articles were read in full and selected for inclusion based on prespecified criteria. Results: Our literature search identified 8683 potential citations, and after duplicate removal, abstract screening, and full-text review, 62 studies remained meeting inclusion and exclusion criteria. Outcomes were extracted according to the location of injury and type of surgical repair. Injuries were classified into isolated femoral nerve injuries, isolated obturator nerve injuries, isolated sciatic nerve injuries, and multilevel LSP injuries. Surgical treatment was further classified into exploration with neurolysis, direct repair, nerve grafting, and nerve transfer surgery. Conclusions: Although results vary based on the location of the injury and the surgical technique used, nerve grafts and transfers demonstrated reasonable success in improving functional and pain outcomes. Overall, isolated femoral and obturator nerve injuries had the best outcomes reported with surgical treatment. Furthermore, incomplete sciatic nerve and multilevel LSP injuries had more reported surgical options and better outcomes than complete sciatic nerve injuries.

Personalized treatments for depressive symptoms in patients with advanced heart failure: A pragmatic randomized controlled trial.

OBJECTIVES: Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months. METHODS: Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed. CONCLUSIONS: The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings. REGISTRATION: ClinicalTrials.Gov Identifier: NCT03688100.

The role of spatial frequency analysis in correlating atomic force microscopy and optical profilometry with self-etch adhesive enamel bond fatigue durability.

The purpose of this study was to: (a) evaluate the role of enamel surface roughness on bond fatigue durability and (b) evaluate statistical differences in roughness values based on measurement technique, including the use of spatial filtering for optical profilometry (OP). OptiBond XTR (Kerr Corp), Prime & Bond elect (DENTSPLY Caulk), Scotchbond Universal (3 M Oral Care), and XTR pre-etched with Ultra-Etch phosphoric acid (35%) (Ultradent) self-etch adhesives were used to treat enamel. A flat ground enamel surface was included as a control. Atomic force microscopy (AFM) and OP were used to measure the surface topography of each enamel surface following the application of adhesives. AFM, OP, and filtered OP (FOP) roughness values, where FOP was designed to only include the lateral spatial resolution consistent with AFM roughness values, were collected. Spatial resolution filtering with OriginPro was used to compare line scans from the two imaging techniques and generate the FOP group. These micro- versus nanoscale lateral roughness values were correlated with shear bond and shear fatigue strengths of the adhesives bonded to enamel. Roughness values showed differences based on measurement technique and strong correlations with bond and fatigue strength. The filtered OP group demonstrated the importance of careful usage and reporting of atomic force microscopy and OP metrics in adhesive dentistry. Best practices for surface roughness analysis were also discussed.

Five-year outcomes of intravitreal drug therapy for neovascular age-related macular degeneration in eyes with baseline vision 20/60 or better.

OBJECTIVE: To assess outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) and good baseline visual acuity (VA) treated using a treat-and-extend (T&E) regimen with intravitreal aflibercept, ranibizumab, or bevacizumab. DESIGN: Single center, retrospective, observational case series. PARTICIPANTS: Ninety-one patients (93 eyes) with nAMD and baseline VA ≥20/60 followed for ≥1 year after the first intravitreal injection. Minimum of 6 (first year) and 3 (subsequent years) and maximum of 12 injections per 12 calendar months. INTERVENTION: Intravitreal aflibercept 2.0 mg, ranibizumab 0.5 mg, or bevacizumab 1.25 mg. Three monthly injections. Treatment interval extended in 2-week increments after resolution of macular edema and reduced in 2-week increments if edema recurred; maximum interval of 12 weeks. Medication changed if edema recurred during and persisted after three monthly injections of original agent. MAIN OUTCOME MEASURES: VA maintenance over time. Total number of injections received by year of treatment. RESULTS: Ninety-three eyes were analyzed. Pretreatment VA was 20/20-20/25 (N=16), 20/30-20/40 (N=47), and 20/50-20/60 (N=30). Mean follow-up was 3.2 years. Follow-up by year was 93, 73, 65, 44, and 26 eyes for years 1-5, respectively. Mean number of injections during years 1-5 was 7.9, 5.9, 5.6, 5.9, and 6.0, respectively; mode number of injections was 7, 5, 3, 6, and 4, respectively. For years 1-5, percent of all eyes at or above baseline was 70%, 66%, 65%, 59%, and 58%, respectively; percent ≥20/60 was 86%, 88%, 86%, 84%, and 77% for years 1-5. For eyes with baseline VA ≥20/40, percent of eyes at or above baseline was 83%, 82%, 81%, 68% and 76% for years 1-5, respectively. CONCLUSION: Using a T&E intravitreal injection protocol, more than 75% of treatment-naive eyes with nAMD and baseline VA ≥20/60 can maintain VA ≥20/60 over 5 years.

The Assessment and Measurement of Wellness in the Clinical Medical Setting: A Systematic Review.

We conducted a systematic review of the published literature relating to the assessment and measurement of wellness in order to answer the following questions: 1) What is the working definition of wellness? 2) What wellness assessment instruments have been evaluated or applied in medical settings? 3) How valid, reliable, and accessible are these wellness assessment tools? The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review. Studies published from1990 to 2016 on wellness assessment were identified through Medline and PsycINFO using the following keywords: "assessment" OR "evaluation" OR "measurement" AND "wellness" OR "wellbeing." Two authors independently conducted a focused analysis then reached a consensus on 23 studies that met the specific selection criteria. This review revealed that there is a lack of uniform definition of wellness. The studies utilizing wellness assessment tools demonstrate strongest reliability values for the following instruments: Wellness Evaluation of Lifestyle, Five-factor Wellness Evaluation of Lifestyle, Perceived Wellness Survey, the Optimal Living Profile, and the Body-Mind-Spirit Wellness Behavior and Characteristic Inventory. However, there is insufficient evidence to support the clinical utility of a single particular wellness instrument. Properly defining wellness might help drive the development and validation of more precise assessment and measurement methods. This could reinforce interventions that promote wellness.

Pain and Depression: A Systematic Review.

BACKGROUND: Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address both pain and depressive symptoms when evaluating treatment options. AIM: To review studies addressing pain comorbid with depression, and to report the impact of current treatments. METHOD: A systematic search of the literature databases was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 28 articles to be included in this review. RESULTS: Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants. Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression. CONCLUSION: The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.

MUTE Directly Orchestrates Cell-State Switch and the Single Symmetric Division to Create Stomata.

Precise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing this event remains unclear. Here we report comprehensive inventories of gene expression by the Arabidopsis bHLH protein MUTE, a potent inducer of stomatal differentiation. MUTE switches the gene expression program initiated by SPEECHLESS. MUTE directly induces a suite of cell-cycle genes, including CYCD5;1, in which introduced expression triggers the symmetric divisions of arrested precursor cells in mute, and their transcriptional repressors, FAMA and FOUR LIPS. The regulatory network initiated by MUTE represents an incoherent type 1 feed-forward loop. Our mathematical modeling and experimental perturbations support a notion that MUTE orchestrates a transcriptional cascade leading to a tightly restricted pulse of cell-cycle gene expression, thereby ensuring the single cell division to create functional stomata.

Major Depression Comorbid with Medical Conditions: Analysis of Quality of Life, Functioning, and Depressive Symptom Severity.

Background: The presence of Major Depressive Disorder (MDD) is often comorbid in patients with a variety of general medical conditions (GMCs) which could lead to less favorable outcomes. Objective: The goal of this analysis is to examine functional outcomes of QOL and functioning before and after antidepressant treatment among patients with MDD with and without GMCs. Methods: We performed a secondary analysis based on the STAR*D database. The analysis included two patient groups from the STAR*D trial: 1,198 patients comorbid with MDD and GMCs (MDD + GMC) and 1,082 patients with MDD and no GMCs (MDDnoGMC), as defined by the Cumulative Illness Rating Scale. We analyzed depressive symptom severity, functioning and quality of life (QOL) before and after level 1 treatment with citalopram. Results: At baseline, the MDD + GMC group had significantly lower QOL (p < 0.001) and functioning (p = 0.001) than the MDDnoGMC group, although depressive symptom severity was not significantly different. Following antidepressant treatment, QOL, functioning and depressive symptom severity significantly improved for both MDD + GMC and MDDnoGMC groups. However, patients with MDD + GMC were more likely to experience severe impairments in QOL in (56.8% vs. 43.5% for MDDnoGMC, p < 0.001) and functioning (42.5% vs. 29.3% for MDDnoGMC, p < 0.001) following treatment. The remission rate was significantly lower for MDD + GMC (30.6% vs. 41.1% for MDDnoGMC, p < 0.001). Conclusions: Our findings suggest that antidepressant treatment had a positive impact on patients with and without GMCs. However, those with GMCs experienced not only a lower remission rate, but also continued to experience more significantly severe impairments in QOL and functioning.

The role of selective serotonin reuptake inhibitors in preventing relapse of major depressive disorder.

The objective of this review was to evaluate the efficacy of selective serotonin reuptake inhibitors (SSRIs) and SSRIs compared with other treatment modalities in preventing relapse after an episode of major depressive disorder (MDD). An Ovid MEDLINE and PsycINFO search (from 1987 to August 2017) was conducted using the following terms: selective serotonin reuptake inhibitors, antidepressants, depression, prevention, prophylaxis, relapse and MDD. Using predefined criteria, two authors independently selected and reached consensus on the included studies. Sixteen articles met the criteria: 10 compared the relapse rate of selective SSRIs with placebo or other SSRIs; one discussed the effectiveness of SSRIs plus psychotherapy, two compared SSRI versus tricyclic antidepressants (TCAs), two were mainly composed of TCAs plus psychotherapy, and one compared SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs). According to the included studies, the relapse risk in adults was lower when SSRIs were combined with psychotherapy. Results comparing SSRIs and SNRIs were inconclusive. TCAs may be equally as effective as SSRIs. Atypical antidepressants (mirtazapine and St John's Wort) had no significant difference in efficacy and remission rates compared with SSRIs. Escitalopram appeared to fare better in efficacy than other SSRIs, owing to a higher prophylactic efficacy and lower side effects; however, according to the current data, this difference was not significant. To conclude, this review provides evidence that continuing SSRIs for 1 year reduces risk of MDD and relapse. Furthermore, the combination of SSRIs and cognitive behavioural therapy may effectively reduce relapse. Escitalopram appeared to yield better results and fewer side effects than did other SSRIs or SNRIs. The effectiveness in reducing relapse of SSRIs was similar to that of TCAs and atypical antidepressants.

Quality of life and functioning of Hispanic patients with Major Depressive Disorder before and after treatment.

BACKGROUND: Similar rates of remission from Major Depressive Disorder (MDD) have been documented between ethnic groups in response to antidepressant treatment. However, ethnic differences in functional outcomes, including patient-reported quality of life (QOL) and functioning, have not been well-characterized. We compared symptomatic and functional outcomes of antidepressant treatment in Hispanic and non-Hispanic patients with MDD. METHODS: We analyzed 2280 nonpsychotic treatment-seeking adults with MDD who received citalopram monotherapy in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression study. All subjects (239 Hispanic, 2041 non-Hispanic) completed QOL, functioning, and depressive symptom severity measures at entry and exit. RESULTS: Hispanic participants had significantly worse QOL scores at entry and exit (p < 0.01). However, after controlling for baseline QOL, there was no difference between Hispanic and non-Hispanic patients' QOL at exit (p = 0.21). There were no significant between-group differences at entry or at exit for depressive symptom severity or functioning. Both groups had significant improvements in depressive symptom severity, QOL, and functioning from entry to exit (all p values < 0.01). Patients with private insurance had lower depressive symptom severity, greater QOL, and better functioning at exit compared to patients without private insurance. LIMITATIONS: This study was a retrospective data analysis, and the Hispanic group was relatively small compared to the non-Hispanic group. CONCLUSIONS: Hispanic and non-Hispanic participants with MDD had similar responses to antidepressant treatment as measured by depressive symptom severity scores, quality of life, and functioning. Nevertheless, Hispanic patients reported significantly worse quality of life at entry.

Quality of Life, Functioning, and Depressive Symptom Severity in Older Adults With Major Depressive Disorder Treated With Citalopram in the STAR*D Study.

OBJECTIVE: Major depressive disorder (MDD) can substantially worsen patient-reported quality of life (QOL) and functioning. Prior studies have examined the role of age in MDD by comparing depressive symptom severity or remission rates between younger and older adults. This study examines these outcomes before and after SSRI treatment. On the basis of prior research, we hypothesized that older adults would have worse treatment outcomes in QOL, functioning, and depressive symptom severity and that nonremitters would have worse outcomes. METHODS: A retrospective secondary data analysis was conducted from the National Institute of Mental Health-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (July 2001-September 2006). We analyzed data for 2,280 nonpsychotic adults with DSM-IV-TR-defined MDD who received citalopram monotherapy. Older adults were classified as adults aged 65 years and above. All subjects completed patient-reported QOL, functioning, and depressive symptom severity measures at entry and exit. Subjects included 106 older adults and 2,174 adults < 65. MDD remission status posttreatment was also determined. RESULTS: Both older adults and adults < 65 experienced significant improvements and medium to large treatment responses across QOL, functioning, and depressive symptom severity (P < .001). Older adults had smaller treatment effect sizes for all outcomes, particularly functioning. Conversely, mean change scores from entry to exit were equivalent across all outcomes. Remitters at exit had significantly better responses to treatment than nonremitters for the majority of outcomes. CONCLUSION: Findings suggest that older adults and younger adults have comparable treatment responses to citalopram monotherapy, with significant improvements in patient-reported depressive symptom severity, functioning, and QOL. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00021528.

Autocrine regulation of stomatal differentiation potential by EPF1 and ERECTA-LIKE1 ligand-receptor signaling.

Development of stomata, valves on the plant epidermis for optimal gas exchange and water control, is fine-tuned by multiple signaling peptides with unique, overlapping, or antagonistic activities. EPIDERMAL PATTERNING FACTOR1 (EPF1) is a founding member of the secreted peptide ligands enforcing stomatal patterning. Yet, its exact role remains unclear. Here, we report that EPF1 and its primary receptor ERECTA-LIKE1 (ERL1) target MUTE, a transcription factor specifying the proliferation-to-differentiation switch within the stomatal cell lineages. In turn, MUTE directly induces ERL1. The absolute co-expression of ERL1 and MUTE, with the co-presence of EPF1, triggers autocrine inhibition of stomatal fate. During normal stomatal development, this autocrine inhibition prevents extra symmetric divisions of stomatal precursors likely owing to excessive MUTE activity. Our study reveals the unexpected role of self-inhibition as a mechanism for ensuring proper stomatal development and suggests an intricate signal buffering mechanism underlying plant tissue patterning.

Analysis of Patient-reported Outcomes of Quality of Life and Functioning Before and After Treatment of Major Depressive Disorder Comorbid With Alcohol Use Disorders.

OBJECTIVE: Alcohol use disorders (AUDs) are common among persons with major depressive disorder (MDD) and have an adverse impact on course of illness and patient outcomes. The aim of this study was to examine whether AUD adversely impacted patient-centered outcomes in a sample of research subjects evaluated as part of a large clinical trial for depression. The outcomes of interest to this post hoc analysis are quality of life (QOL), functioning, and depressive symptom severity. METHODS: We analyzed 2280 adult MDD outpatient research subjects using data from the Sequenced Treatment Alternatives to Relieve Depression trial. We compared entry and post-selective serotonin reuptake inhibitors (SSRI) treatment QOL, functioning, and depressive symptom severity scores between 121comorbid MDD with AUD (MDD + AUD) subjects and 2159 MDD-no-AUD subjects, and also differences between subjects categorized as remitters versus nonremitters within each group at exit. RESULTS: At entry, MDD + AUD subjects reported similar QOL, functioning, and depressive symptom severity compared with the MDD-no-AUD subjects. After treatment with citalopram, both groups showed significant improvements throughout treatment; however, 36% to 55% of subjects still suffered from severely impaired QOL and functioning at exit. CONCLUSIONS: The overall study population demonstrated a significant response to treatment with large effect sizes in depressive symptom reduction, but to a lesser extent in QOL and functioning. Findings suggest that subjects with MDD + AUD benefited equally as MDD-no-AUD from treatment with selective serotonin reuptake inhibitors (SSRI) medication, yet both groups continue to experience reduced QOL and functioning after treatment. Monitoring QOL and functioning is critical to determine whether interventions that improve clinical outcomes also impact patient-centered outcomes, and our analysis suggests that there is a pressing need for innovative interventions that effectively improve these outcomes.

Trazodone for Insomnia: A Systematic Review.

OBJECTIVE: While trazodone is approved for the treatment of depression, the off-label use of this medication for insomnia has surpassed its usage as an antidepressant. In this systematic review, we examined the evidence for the efficacy and safety of trazodone for insomnia. METHODS: A literature search was conducted using MEDLINE/PubMed databases from the past 33 years (1983-2016) and the keywords insomnia, trazodone, sedative, treatment, and hypnotics. The results were restricted to English language and human subjects. All randomized clinical trials, meta-analyses, observational studies, and placebo-controlled trials regarding trazodone for the treatment of primary or secondary insomnia were reported, per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The study selection process yielded a total of 45 studies. RESULTS: Evidence for the efficacy of trazodone has been repeatedly demonstrated for primary insomnia, as well as secondary insomnia, including for symptoms that are a result of depression, dementia, and being a healthy man. Earlier studies (1980-2000) focused on utilizing trazodone at high doses (≥100mg/d) for the treatment of insomnia among the depressed population; however, since the 2000s, the utility of trazodone has been expanded to treat secondary insomnia among the non-depressed population as well. The side effects are dose-dependent, and the most common is drowsiness. CONCLUSION: A review of the literature suggests that there are adequate data supporting the efficacy and general safety of the low-dose use of trazodone for the treatment of insomnia.

A Negative Feedback Loop between PHYTOCHROME INTERACTING FACTORs and HECATE Proteins Fine-Tunes Photomorphogenesis in Arabidopsis.

The phytochrome interacting factors (PIFs), a small group of basic helix-loop-helix transcription factors, repress photomorphogenesis both in the dark and light. Light signals perceived by the phytochrome family of photoreceptors induce rapid degradation of PIFs to promote photomorphogenesis. Here, we show that HECATE (HEC) proteins, another small group of HLH proteins, antagonistically regulate PIFs to promote photomorphogenesis. HEC1 and HEC2 heterodimerize with PIF family members. PIF1, HEC1, and HEC2 genes are spatially and temporally coexpressed, and HEC2 is localized in the nucleus. hec1, hec2, and hec3 single mutants and the hec1 hec2 double mutant showed hyposensitivity to light-induced seed germination and accumulation of chlorophyll and carotenoids, hallmark processes oppositely regulated by PIF1. HEC2 inhibits PIF1 target gene expression by directly heterodimerizing with PIF1 and preventing DNA binding and transcriptional activation activity of PIF1. Conversely, PIFs directly activate the expression of HEC1 and HEC2 in the dark, and light reduces the expression of these HECs possibly by degrading PIFs. HEC2 is partially degraded in the dark through the ubiquitin/26S-proteasome pathway and is stabilized by light. HEC2 overexpression also reduces the light-induced degradation of PIF1. Taken together, these data suggest that PIFs and HECs constitute a negative feedback loop to fine-tune photomorphogenesis in Arabidopsis thaliana.

Self-Actuation of Liquid Metal via Redox Reaction.

Presented here is a method for actuating a gallium-based liquid-metal alloy without the need for an external power supply. Liquid metal is used as an anode to drive a complementary oxygen reduction reaction, resulting in the spontaneous growth of hydrophilic gallium oxide on the liquid-metal surface, which induces flow of the liquid metal into a channel. The extent and duration of the actuation are controllable throughout the process, and the induced flow is both reversible and repeatable. This self-actuation technique can also be used to trigger other electrokinetic or fluidic mechanisms.

Effect of lanthanide complex structure on cell viability and association.

A systematic study of the effect of hydrophobicity and charge on the cell viability and cell association of lanthanide metal complexes is presented. The terbium luminescent probes feature a macrocyclic polyaminocarboxylate ligand (DOTA) in which the hydrophobicity of the antenna and that of the carboxyamide pendant arms are independently varied. Three sensitizing antennas were investigated in terms of their function in vitro: 2-methoxyisophthalamide (IAM(OMe)), 2-hydroxyisophthalamide (IAM), and 6-methylphenanthridine (Phen). Of these complexes, Tb-DOTA-IAM exhibited the highest quantum yield, although the higher cell viability and more facile synthesis of the structurally related Tb-DOTA-IAM(OMe) platform renders it more attractive. Further modification of this latter core structure with carboxyamide arms featuring hydrophobic benzyl, hexyl, and trifluoro groups as well as hydrophilic amino acid based moieties generated a family of complexes that exhibit high cell viability (ED50 > 300 µM) regardless of the lipophilicity or the overall complex charge. Only the hexyl-substituted complex reduced cell viability to 60% in the presence of 100 µM complex. Additionally, cellular association was investigated by ICP-MS and fluorescence microscopy. Surprisingly, the hydrophobic moieties did not increase cell association in comparison to the hydrophilic amino acid derivatives. It is thus postulated that the hydrophilic nature of the 2-methoxyisophthalamide antenna (IAM(OMe)) disfavors the cellular association of these complexes. As such, responsive luminescent probes based on this scaffold would be appropriate for the detection of extracellular species.