A New Empirical Definition of Major Depressive Episode Recovery and Its Positive Impact on Future Course of Illness.

Objective: To provide the first head-to-head test of the predictive validity of 2 resolution levels included in the current consensus definition of major depressive episode (MDE) recovery and provide an empirically based, clinically useful definition of the end of an MDE.

Method: 322 participants entering the National Institute of Mental Health Collaborative Depression Study with MDE (diagnosed by Research Diagnostic Criteria) in 1978-1981, and followed thereafter for up to 31 years, were divided into those with 8 consecutive weeks of asymptomatic MDE recovery or residual subsyndromal depressive symptom (SSD) resolution of their index MDE. These 2 levels of recovery were defined based on weekly symptom status on all depressive conditions, assessed by Longitudinal Interval Follow-Up Evaluation (LIFE) interviews conducted every 6 months.

Narrowing the gaps between what we know and what we do in psychiatry.

There are many important research-practice gaps. Evidence to inform clinical decision-making is remarkably scant. A greater research focus on more clinically informative patient samples, clinically relevant questions, the use of innovative trial designs and analyses, and reporting of results in clinically understandable and potentially actionable ways can help reduce these gaps.

Thyroid Autoimmune Antibodies and Major Depressive Disorder in Women.

Introduction: Anti-thyroid antibodies are associated with extra-thyroid diseases such as Graves' ophthalmopathy and Hashimoto's encephalopathy. Some evidence suggests that anti-thyroid antibodies are also associated with depression. Interleukin (IL)-17 appears to play an important role in autoimmune thyroid disease.

Baseline Depression Severity as Moderator of Depression Outcomes Between Cognitive Behavioral Therapy vs Pharmacotherapy: An Individual Patient Data Meta-analysis.

Importance: Current guidelines recommend treating severe depression with pharmacotherapy. Randomized clinical trials as well as traditional meta-analyses have considerable limitations in testing for moderators of treatment outcomes.

Objectives: To conduct a systematic literature search, collect primary data from trials, and analyze baseline depression severity as a moderator of treatment outcomes between cognitive behavioral therapy (CBT) and antidepressant medication (ADM).

A quantitative radioluminographic imaging method for evaluating lateral diffusion rates in skin.

A method is presented for measuring the lateral diffusion coefficients of exogenously applied compounds on excised skin. The method involves sequential high resolution imaging of the spatial distribution of β-radiation associated with [(14)C]-labeled compounds to monitor the development of the concentration profile on the skin surface. It is exemplified by measurements made on three radiolabeled test compounds--caffeine, testosterone, and zinc pyrithione (ZnPT)--administered as solutions.

Opinions of Young Adults on Re-Consenting for Biobanking.

Objective: To evaluate young adult cancer survivor opinions on whether their biobanked tissue and associated de-identified clinical data obtained during their childhood should require re-consent at the age of majority, when parental consent was originally provided.

Study Design: Thirty young adults (18-34 years old), who were former pediatric oncology patients of The Children's Hospital at Westmead with stored research biospecimens, were recruited. They completed a semistructured interview, which included questions on biobanking re-consent, awareness of biobanked tissue, satisfaction about banked tissue, and independence within the family.

Expression of five acetylcholine receptor subunit genes in Brugia malayi adult worms.

Acetylcholine receptors (AChRs) are required for body movement in parasitic nematodes and are targets of "classical" anthelmintic drugs such as levamisole and pyrantel and of newer drugs such as tribendimidine and derquantel. While neurotransmission explains the effects of these drugs on nematode movement, their effects on parasite reproduction are unexplained. The levamisole AChR type (L-AChRs) in Caenorhabditis elegans is comprised of five subunits: Cel-UNC-29, Cel-UNC-38, Cel-UNC-63, Cel-LEV-1 and Cel-LEV-8.

Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder.

Background: Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs.

Methods: 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER.

Biobank classification in an Australian setting.

In 2011, Watson and Barnes proposed a schema for classifying biobanks into 3 groups (mono-, oligo-, and poly-user), primarily based upon biospecimen access policies. We used results from a recent comprehensive survey of cancer biobanks in New South Wales, Australia to assess the applicability of this biobank classification schema in an Australian setting. Cancer biobanks were identified using publically available data, and by consulting with research managers.

Surgical follow-up costs disproportionately impact low-income patients.

Background: Surgical procedures have significant costs at the national level, but the financial burden on patients is equally important. Patients' out-of-pocket costs for surgery and surgical care include not only direct medical costs but also the indirect cost of lost wages and direct nonmedical costs including transportation and childcare. We hypothesized that the nonmedical costs of routine postoperative clinic visits disproportionately impact low-income patients.

A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder.

Objective: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use.

Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial.

Objective: The study aims were 1) to describe the proportions of individuals who met criteria for melancholic, atypical, and anxious depressive subtypes, as well as subtype combinations, in a large sample of depressed outpatients, and 2) to compare subtype profiles on remission and change in depressive symptoms after acute treatment with one of three antidepressant medications.

Method: Participants 18-65 years of age (N=1,008) who met criteria for major depressive disorder were randomly assigned to 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine. Participants were classified by subtype.

Toward an online cognitive and emotional battery to predict treatment remission in depression.

Purpose: To evaluate the performance of a cognitive and emotional test battery in a representative sample of depressed outpatients to inform likelihood of remission over 8 weeks of treatment with each of three common antidepressant medications.

Patients And Methods: Outpatients 18-65 years old with nonpsychotic major depressive disorder (17 sites) were randomized to escitalopram, sertraline or venlafaxine-XR (extended release). Participants scored ≥12 on the baseline 16-item Quick Inventory of Depressive Symptomatology - Self-Report and completed 8 weeks of treatment.

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.

The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment.

We aimed to characterize a large international cohort of outpatients with MDD within a practical trial design, in order to identify clinically useful predictors of outcomes with three common antidepressant medications in acute-phase treatment of major depressive disorder (MDD). The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). At pre-treatment, we characterized participants by symptoms, clinical history, functional status and comorbidity.

A cognitive-emotional biomarker for predicting remission with antidepressant medications: a report from the iSPOT-D trial.

Depression involves impairments in a range of cognitive and emotional capacities. It is unknown whether these functions can inform medication choice when considered as a composite predictive biomarker. We tested whether behavioral tests, grounded in the neurobiology of cognitive and emotional functions, predict outcome with common antidepressants.

Pre-treatment insomnia as a predictor of single and combination antidepressant outcomes: a CO-MED report.

Background: Most patients with major depressive disorder (MDD) report clinically significant sleep problems. Pre-treatment insomnia has been associated with poorer treatment outcomes in some antidepressant trials, leading to suggestions that combined treatment regimens may be more successful in this subgroup. This study investigated this question using data from the CO-MED trial.

Stimuli-responsive nanomaterials for biomedical applications.

Nature employs a variety of tactics to precisely time and execute the processes and mechanics of life, relying on sequential sense and response cascades to transduce signaling events over multiple length and time scales. Many of these tactics, such as the activation of a zymogen, involve the direct manipulation of a material by a stimulus. Similarly, effective therapeutics and diagnostics require the selective and efficient homing of material to specific tissues and biomolecular targets with appropriate temporal resolution.

Peptides displayed as high density brush polymers resist proteolysis and retain bioactivity.

We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is explored by studying the proteolytic resistance of brush polymers composed of peptides that are substrates for either thrombin or a metalloprotease.

Cognitive Testing to Identify Children With ADHD Who Do and Do Not Respond to Methylphenidate.

Objective: To explore the utility of cognitive measures for predicting response of children and adolescents to methylphenidate (MPH).

Method: Participants from the International Study to Predict Optimized Treatment-in ADHD (iSPOT-A) completed a cognitive test battery prior to receiving 6 weeks of MPH. The responder criterion was a 25% reduction in ADHD-Rating Scale-IV scores.

Poly(oligonucleotide).

Here we report the preparation of poly(oligonucleotide) brush polymers and amphiphilic brush copolymers from nucleic acid monomers via graft-through polymerization. We describe the polymerization of PNA-norbornyl monomers to yield poly-PNA (poly(peptide nucleic acid)) via ring-opening metathesis polymerization (ROMP) with the initiator, (IMesH2)(C5H5N)2(Cl)2RuCHPh.1 In addition, we present the preparation of poly-PNA nanoparticles from amphiphilic block copolymers and describe their hybridization to a complementary single-stranded DNA (ssDNA) oligonucleotide.

High level expression of a glutamate-gated chloride channel gene in reproductive tissues of Brugia malayi may explain the sterilizing effect of ivermectin on filarial worms.

Glutamate-gated chloride channels (GluCl) are targets for avermectin/milbemycin (A/M) anthelmintics such as ivermectin that cause paralysis of somatic and pharyngeal muscles in gastrointestinal nematodes. Ivermectin is useful for onchocerciasis control programs because of its activity against microfilariae that often cause ocular disease and severe dermatitis. However, mechanisms responsible for reduced microfilaria production by adult worms following ivermectin treatment are poorly understood.