Dysphoric Milk Ejection Reflex in Human Lactation: An Integrative Literature Review.

BACKGROUND: Dysphoric Milk Ejection Reflex is an understudied condition of lactation involving emotional dysregulation during letdown or milk ejection. Affected individuals may experience transient feelings of helplessness, melancholy, and general unhappiness. RESEARCH AIM: To evaluate the scope of published literature on Dysphoric Milk Ejection Reflex. METHOD: Whittemore and Knafl's methodology guided this integrative review. Five databases were searched for primary research, summaries, and editorials on Dysphoric Milk Ejection Reflex in lactating individuals. Literature searched also included websites, pamphlets, and conference proceedings via Google and Google Scholar. A total of 11 articles, from five different countries, met inclusion criteria for review. RESULTS: Studies on Dysphoric Milk Ejection Reflex and negative emotional sensations during lactation were synthesized under five conceptual umbrellas: (1) Experiences, Sensations, and Symptom Management; (2) Biological Underpinnings; (3) Influence on Maternal Role and Breastfeeding Self-Efficacy; (4) Support, Understanding, and Awareness; and (5) Reduction and Cessation of Breastfeeding. CONCLUSION: Dysphoric Milk Ejection Reflex is a neurobiological condition characterized by low mood and negative feelings during milk ejection throughout lactation. Dysphoric Milk Ejection Reflex is linked to maternal psychological distress and breastfeeding discontinuation. Priority areas for future research include biological origins and interventions aimed at prevention, symptom control, and greater awareness of the condition on a more international scope.

Ligand-independent oligomerization of TACI is controlled by the transmembrane domain and regulates proliferation of activated B cells.

In mature B cells, TACI controls class-switch recombination and differentiation into plasma cells during T cell-independent antibody responses. TACI binds the ligands BAFF and APRIL. Approximately 10% of patients with common variable immunodeficiency (CVID) carry TACI mutations, of which A181E and C172Y are in the transmembrane domain. Residues A181 and C172 are located on distinct sides of the transmembrane helix, which is predicted by molecular modeling to spontaneously assemble into trimers and dimers. In human B cells, these mutations impair ligand-dependent (C172Y) and -independent (A181E) TACI multimerization and signaling, as well as TACI-enhanced proliferation and/or IgA production. Genetic inactivation of TACI in primary human B cells impaired survival of CpG-activated cells in the absence of ligand. These results identify the transmembrane region of TACI as an active interface for TACI multimerization in signal transduction, in particular for ligand-independent signals. These functions are perturbed by CVID-associated mutations.

Study protocol for a randomised controlled trial evaluating an evidence-based, stepped and coordinated care service model for mental disorders (RECOVER).

INTRODUCTION: Healthcare systems around the world are looking for solutions to the growing problem of mental disorders. RECOVER is the synonym for an evidence-based, stepped and cross-sectoral coordinated care service model for mental disorders. RECOVER implements a cross-sectoral network with managed care, comprehensive psychological, somatic and social diagnostics, crisis resolution and a general structure of four severity levels, each with assigned evidence-based therapy models (eg, assertive community treatment) and therapies (eg, psychotherapy). The study rationale is the investigation of the effectiveness and efficiency of stepped and integrated care in comparison to standard care. METHODS AND ANALYSIS: The trial is conducted in accordance to the Standard Protocol Items: Recommendations for Interventional Trials Statement. The study aims to compare the RECOVER model with treatment as usual (TAU). The following questions are examined: Does RECOVER reduce healthcare costs compared with TAU? Does RECOVER improve patient-relevant outcomes? Is RECOVER cost-effective compared with TAU? A total sample of 890 patients with mental disorders will be assessed at baseline and individually randomised into RECOVER or TAU. Follow-up assessments are conducted after 6 and 12 months. As primary outcomes, cost reduction, improvement in symptoms, daily functioning and quality of life as well as cost-effectiveness ratios will be measured. In addition, several secondary outcomes will be assessed. Primary and secondary outcomes are evaluated according to the intention-to-treat principle. Mixed linear or logistic regression models are used with the direct maximum likelihood estimation procedure which results in unbiassed estimators under the missing-at-random assumption. Costs due to healthcare utilisation and productivity losses are evaluated using difference-in-difference regressions. ETHICS AND DISSEMINATION: Ethical approval from the ethics committee of the Hamburg Medical Association has been obtained (PV5672). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications. TRIAL REGISTRATION NUMBER AND REGISTRY NAME: ClinicalTrials.gov (NCT03459664), RECOVER PROTOCOL VERSION: 19 March 2020 (V.3.0).