Loss of Twist1 and balanced retinoic acid signaling from the meninges causes cortical folding in mice.

Secondary lissencephaly evolved in mice due to effects on neurogenesis and the tangential distribution of neurons. Signaling pathways that help maintain lissencephaly are still poorly understood. We show that inactivating Twist1 in the primitive meninges causes cortical folding in mice. Cell proliferation in the meninges is reduced, causing loss of arachnoid fibroblasts that express Raldh2, an enzyme required for retinoic acid synthesis. Regionalized loss of Raldh2 in the dorsolateral meninges is first detected when folding begins. The ventricular zone expands and the forebrain lengthens at this time due to expansion of apical radial glia. As the cortex expands, regionalized differences in the levels of neurogenesis are coupled with changes to the tangential distribution of neurons. Consequentially, cortical growth at and adjacent to the midline accelerates with respect to more dorsolateral regions, resulting in cortical buckling and folding. Maternal retinoic acid supplementation suppresses cortical folding by normalizing forebrain length, neurogenesis and the tangential distribution of neurons. These results suggest that Twist1 and balanced retinoic acid signaling from the meninges are required to maintain normal levels of neurogenesis and lissencephaly in mice.

Recurrent Implication of Striatal Cholinergic Interneurons in a Range of Neurodevelopmental, Neurodegenerative, and Neuropsychiatric Disorders.

Cholinergic interneurons are "gatekeepers" for striatal circuitry and play pivotal roles in attention, goal-directed actions, habit formation, and behavioral flexibility. Accordingly, perturbations to striatal cholinergic interneurons have been associated with many neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The role of acetylcholine in many of these disorders is well known, but the use of drugs targeting cholinergic systems fell out of favor due to adverse side effects and the introduction of other broadly acting compounds. However, in response to recent findings, re-examining the mechanisms of cholinergic interneuron dysfunction may reveal key insights into underlying pathogeneses. Here, we provide an update on striatal cholinergic interneuron function, connectivity, and their putative involvement in several disorders. In doing so, we aim to spotlight recurring physiological themes, circuits, and mechanisms that can be investigated in future studies using new tools and approaches.

Experiences of breast feeding at work for physicians, residents and medical students: a scoping review.

OBJECTIVE: To review and summarise the available literature regarding breastfeeding experiences of medical students, residents and physicians. ELIGIBILITY CRITERIA: Articles of any design, including non-peer reviewed data that examine the experiences of breast feeding of medical students, residents and staff physicians. INFORMATION SOURCES: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid EMBASE, Scopus and Web of Science. RISK OF BIAS: All peer-reviewed studies underwent risk-of-bias assessment using relevant tools, depending on the study design. INCLUDED STUDIES: We included 71 citations; 51 surveys, 3 narrative descriptions, 9 editorials or letters to the editor, and 3 reviews. SYNTHESIS OF RESULTS: Included articles were heterogeneous with respect to their study design, target population and outcomes reported. Most articles had a high risk of bias. Only five articles reported the impact of an intervention. DESCRIPTION OF EFFECT: Despite heterogeneity, the majority of articles described important barriers to breast feeding for physicians, residents and medical students. These barriers were similar across studies, and included inadequate and inaccessible space, time constraints and inflexible scheduling, and lack of colleague support. The consequences of these barriers included low milk supply and early discontinuation of breast feeding. STRENGTHS AND LIMITATIONS OF EVIDENCE: Due to the observed heterogeneity of articles identified in this review, we are unable to assess trends in barriers or duration of breastfeeding over time. INTERPRETATION: Interventions to overcome systemic and cultural barriers to breast feeding are needed to meet legal obligations of workplaces for physicians and trainees. These interventions should be formally evaluated using implementation science or quality improvement methods.