A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders.

Suicide is the second leading cause of death in the United States among individuals aged 10-24, and severe youth depression is often refractory to the current standards of care. Many studies have demonstrated the efficacy of ketamine in reducing depressive symptoms in adults with treatment-resistant mood disorders, though few studies utilizing ketamine in youth populations exist. This systematic review examines the current state of evidence for ketamine use in children with treatment-resistant mood disorders. We conducted a search utilizing two electronic databases for English-language studies investigating the therapeutic effects and side effect profile of ketamine in youth ≤ 19 years of age with a diagnosis of a treatment-resistant mood disorder. Analysis included subjects with treatment-resistant depression with and without psychotic features and with bipolar disorder. Primary outcome measures included the following scales: Montgomery-Asberg Depression Rating Scale, Children's Depression Rating Scale, Children's Depression Rating Scale Revised, Child Bipolar Questionnaire, Overt Aggression Scale, Yale-Brown Obsessive-Compulsive Scale, and Scale for Suicidal Ideation. Four published studies were identified that investigated therapeutic ketamine use in youth for the primary purpose of treating a treatment-resistant psychiatric disorder. Three additional studies that did not meet eligibility criteria were identified and discussed. Ketamine was shown in youth to generally improve depressive symptoms, decrease acute suicidality, and reduce mood lability, though a number of subjects remained resistant to its treatment. These findings substantiate the need for further longitudinal studies investigating ketamine's long-term safety, its efficacy, and abuse potential in the youth.

IL-17 producing mast cells promote the expansion of myeloid-derived suppressor cells in a mouse allergy model of colorectal cancer.

Food allergy can influence the development of colorectal cancer, although the underlying mechanisms are unclear. While mast cells (MC) store and secrete histamine, immature myeloid cells (IMC) are the major site of histidine decarboxylase (HDC) expression, the enzyme responsible for histamine production. From our earlier work, we hypothesized that histamine is central to the association between allergy and colorectal carcinogenesis through its influence on the MC-MDSC axis. Here, we show that in wild type (WT) mice, ovalbumin (OVA) immunization elicits a typical TH2 response. In contrast, in HDC-/- mice, the response to OVA allergy is skewed towards infiltration by IL-17 expressing MCs. This response is inhibited by histamine treatment. The HDC-/- allergic IL-17-expressing MCs promote MDSC proliferation and upregulation of Cox-2 and Arg-1. OVA allergy in HDC-/- mice increases the growth of colon tumor cells in both the MC38 tumor cell implantation model and the AOM/DSS carcinogenesis model. Taken together, our results show that histamine represses IL-17-expressing MCs and their subsequent activation of MDSCs, attenuating the risk of colorectal cancer in the setting of food allergy. Targeting the MC-MDSC axis may be useful for cancer prevention and treatment in patients, particularly in those with food allergy.

Lessons learned from undergraduate students in designing a science-based course in bioethics.

Columbia University offers two innovative undergraduate science-based bioethics courses for student majoring in biosciences and pre-health studies. The goals of these courses are to introduce future scientists and healthcare professionals to the ethical questions they will confront in their professional lives, thus enabling them to strategically address these bioethical dilemmas. These courses incorporate innovative pedagogical methods, case studies, and class discussions to stimulate the students to think creatively about bioethical issues emerging from new biotechnologies. At the end of each course, each student is required to submit a one-page strategy detailing how he or she would resolve a bioethical dilemma. Based on our experience in teaching these courses and on a qualitative analysis of the students' reflections, we offer recommendations for creating an undergraduate science-based course in bioethics. General recommendations include: 1) integrating the science of emerging biotechnologies, their ethical ramifications, and contemporary bioethical theories into interactive class sessions; 2) structuring discussion-based classes to stimulate students to consider the impact of their moral intuitions when grappling with bioethical issues; and 3) using specific actual and futuristic case studies to highlight bioethical issues and to help develop creative problem-solving skills. Such a course sparks students' interests in both science and ethics and helps them analyze bioethical challenges arising from emerging biotechnologies.