Treatment of Bipolar Depression: Evolving Recommendations.

Bipolar depression is the most common and difficult-to-treat phase of bipolar disorder. Antidepressants for unipolar depression are among the most widely used drugs, but recent data and meta-analyses indicate a lack of efficacy. Many of the drugs discussed here are graded provisionally for the strength of the findings in the literature, safety and tolerability, and likely utility of use in patients with bipolar disorder.

Glyphosate residues in rural groundwater, Nottawasaga River Watershed, Ontario, Canada.

Background: The objective of this study was to investigate the occurrence of glyphosate residues (glyphosate and its metabolite AMPA) in shallow groundwater in a catchment dominated by agriculture, and to examine the potential for this groundwater to store and transmit these compounds to surface waters.

Results: Glyphosate residues were found in some of the groundwater samples collected in riparian (surface seeps), upland (mostly <20 m below ground) and wetland settings (<3 m below ground). Overall, glyphosate and AMPA were detected in 10.

Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect.

Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88.

'To preserve unity while almost allowing for chaos': Testing the aesthetic principle of unity-in-variety in product design.

Unity-in-variety is considered to be one of the oldest-known universal principles of beauty. However, little empirical research exists on how unity and variety together influence aesthetic appreciation. In three studies we investigated how unity and variety predict the aesthetic appreciation of a range of product designs, and further assessed whether perceived visual complexity and individual differences in regulatory focus influence this relationship.

More illness in offspring of bipolar patients from the U.S. compared to Europe.

Background: Evidence suggests that patients with bipolar disorder from the United States have an earlier age of onset and a more difficult course of illness than those from Germany and the Netherlands. These characteristics were related to a greater family burden of psychiatric illness and the experience of more psychosocial adversity in childhood. We hypothesized that this greater illness burden would extend to the offspring of the US patients.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

Objectives: Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association.

Multigenerational Positive Family History of Psychiatric Disorders Is Associated With a Poor Prognosis in Bipolar Disorder.

The authors assessed how family history loading affected the course of illness in patients from the United States. A total of 676 outpatients with bipolar disorder from the United States rated their illness and provided a parental and grandparental history of mood disorder, substance abuse, and other clinical conditions. A positive family history for each illness was associated with almost all of the seven poor prognosis factors established in the study (abuse in childhood, early onset, anxiety and substance abuse comorbidity, rapid cycling, multiple episodes, and worsening of severity or frequency of episodes).

Heading off depressive illness evolution and progression to treatment resistance.

Viewing recurrent depression as a potentially progressive illness may help transform treatment toward earlier, more consistent intervention and prevention. Evidence indicates that recurrent stressors, episodes of depression, and bouts of substance abuse can each show sensitization (increased reactivity upon repetition) and cross-sensitization to the others, and drive illness progression and treatment resistance. These long-lasting increases in pathological responsivity appear to be mediated by epigenetic mechanisms involving alterations in chemical marks placed on DNA and histories.

Making Sense of Optogenetics.

This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically-defined neurons with light. Cells are first genetically engineered to express a light-sensitive opsin, which is typically an ion channel, pump, or G protein-coupled receptor. When engineered cells are then illuminated with light of the correct frequency, opsin-bound retinal undergoes a conformational change that leads to channel opening or pump activation, cell depolarization or hyperpolarization, and neural activation or silencing.

Patient Understanding of Body Mass Index (BMI) in Primary Care Practices: A Two-State Practice-based Research (PBR) Collaboration.

Background: The concept of body mass index (BMI) may not be well understood by patients. The purpose of this study was to evaluate patients' knowledge of BMI in the primary care setting.

Methods: Adult patients seen in 18 practices in West Virginia and New Jersey were invited to complete a voluntary survey.

Increases in multiple psychiatric disorders in parents and grandparents of patients with bipolar disorder from the USA compared with The Netherlands and Germany.

Objective: We previously found that compared with Europe more parents of the USA patients were positive for a mood disorder, and that this was associated with early onset bipolar disorder. Here we examine family history of psychiatric illness in more detail across several generations.

Methods: A total of 968 outpatients (average age 41) with bipolar disorder from four sites in the USA and three in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic and family history information on a patient questionnaire.

Accuracy of Hereditary Diffuse Gastric Cancer Testing Criteria and Outcomes in Patients With a Germline Mutation in CDH1.

Background & Aims: Germline mutations in the cadherin 1, type 1, E-cadherin gene (CDH1) cause a predisposition to gastric cancer. We evaluated the ability of the internationally accepted hereditary diffuse gastric cancer (HDGC) criteria to identify individuals with pathogenic mutations in CDH1, and assessed their outcomes. The criteria were as follows: families with 2 or more cases of gastric cancer, with at least 1 patient diagnosed with diffuse gastric cancer (DGC) before age 50; families with 3 or more cases of DGC; families with 1 DGC before the age of 40; and families with a history of DGC and lobular breast cancer, with 1 diagnosis before the age of 50.

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50).

Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer.

Unlabelled: Tumor growth in the context of EGFR inhibitor resistance may remain EGFR-dependent and is mediated by mechanisms including compensatory ligand upregulation and de novo gene alterations. Sym004 is a two-antibody mixture targeting nonoverlapping EGFR epitopes. In preclinical models, Sym004 causes significant EGFR internalization and degradation, which translates into superior growth inhibition in the presence of ligands.

Onchocerciasis transmission in Ghana: persistence under different control strategies and the role of the simuliid vectors.

Background: The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control.

Assessments of the transmission of Onchocerca volvulus by Simulium sanctipauli in the Upper Denkyira District, Ghana, and the intermittent disappearance of the vector.

Following studies on the transmission of Onchocerca volvulus (Leuckart) by Simulium sanctipauli Vajime & Dunbar (Diptera, Simuliidae) in Upper Denkyira District in Ghana in 2001 and 2002 (Kutin et al., Med Vet Ent 18:167-173, 2004), further assessments were carried out in 2006 and 2013/2014 to determine whether transmission parameters had changed since community-directed ivermectin treatment (CDTI) began in 1999. There were no marked changes of the transmission intensities in 2006.

Trauma in sub-Saharan Africa: review of cost, estimation methods, and interventions.

Trauma is a widely acknowledged problem facing individuals and communities in developing countries. In sub-Saharan Africa-a region that is home to some of the world's worst human rights violations, ethnic and civil conflicts, disease epidemics, and conditions of poverty-trauma is an all-too-common experience in citizens' daily lives. In order to address these conditions effectively, the impact of trauma must be understood.

Simultaneous decomposition of multiple hyperspectral data sets: signal recovery of unknown fluorophores in the retinal pigment epithelium.

Upon excitation with different wavelengths of light, biological tissues emit distinct but related autofluorescence signals. We used non-negative matrix factorization (NMF) to simultaneously decompose co-registered hyperspectral emission data from human retinal pigment epithelium/Bruch's membrane specimens illuminated with 436 and 480 nm light. NMF analysis was initialized with Gaussian mixture model fits and constrained to provide identical abundance images for the two excitation wavelengths.

The molecular background of mucinous carcinoma beyond MUC2.

The increasing interest of the oncology community in tumour classification and prediction of outcome to targeted therapies has put emphasis on an improved identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a subtype that is characterized by the presence of abundant extracellular mucin that comprises at least 50% of the tumour volume and is found in 10-15% of colorectal cancer patients. MC development is poorly understood, however, the distinct clinical and pathological presentation of MC suggests a deviant development and molecular background.

Controversies in the psychopharmacology of bipolar disorder.

Few studies have examined the decision-making process for selecting a mood stabilizer or antipsychotic for patients with bipolar disorder. Despite a lack of evidence regarding their efficacy, conventional unimodal antidepressants continue to be used in bipolar treatment regimens. This article examines pharmacologic principles that can facilitate the evidence-based use of mood stabilizers and antipsychotics in patients with bipolar disorder.

Gastric cancer in three relatives of a patient with a biallelic IL12RB1 mutation.

IL-12Rβ1 deficiency, also known as immunodeficiency 30 (IMD30, OMIM 614891), is a rare immunodeficiency syndrome caused by biallelic mutations in IL12RB1. Three second-degree relatives of a patient with this syndrome, all women, developed intestinal-type gastric cancer (GC). In the Netherlands the incidence of non-cardia GC in women is only 7 per 100,000 person years.