Human organoid model systems lack important cell types that, in the embryo, are incorporated into organ tissues during development. We developed an organoid assembly approach starting with cells from ...the three primary germ layers—enteric neuroglial, mesenchymal, and epithelial precursors—that were derived separately from human pluripotent stem cells (PSCs). From these three cell types, we generated human antral and fundic gastric tissue containing differentiated glands surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered antral tissue. Using this experimental system, we show that human enteric neural crest cells (ENCCs) promote mesenchyme development and glandular morphogenesis of antral stomach organoids. Moreover, ENCCs can act directly on the foregut to promote a posterior fate, resulting in organoids with a Brunner’s gland phenotype. Thus, germ layer components that are derived separately from PSCs can be used for tissue engineering to generate complex human organoids.
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•Human stem cell-derived lineages combine to generate multi-layer gastric organoids•3-germ-layer gastric organoids form glands and functionally innervated smooth muscle•Neural crest cells promote growth, patterning, and morphogenesis of gastric tissues•3-germ-layer tissue engineering also generates complex fundic and esophageal organoids
Eicher et al. have generated complex 3-germ-layer human gastric organoids from pluripotent stem cells. These 3-germ-layer organoids contain glandular epithelium surrounded by multiple organized layers of functionally innervated smooth muscle. Manipulating this system revealed key developmental roles of neural crest cells on gastric epithelium and mesenchyme.
Advance care planning (ACP) discussions often occur in the inpatient setting when patients are too ill to participate in decision making. Although the outpatient setting is the preferred time to ...begin these discussions, few physicians do so in practice. Many internal medicine (IM) residents report inadequate training as a barrier to having outpatient ACP discussions.
To assess whether a novel curriculum entitled Goals of Care Ambulatory Resident Education (GOCARE) improved resident physicians' understanding of and preparedness for conducting ACP discussions in the outpatient setting.
The curriculum was delivered over four weekly three-hour small group sessions to IM residents. Each session included didactics, a demonstration of skills, and a simulated patient communication laboratory that emphasized deliberate practice.
IM residents from an urban, academic ambulatory care practice.
Impact of the intervention was evaluated using a retrospective pre-post design. Residents completed surveys immediately after the course and six months later.
Forty-two residents participated in the curriculum and 95% completed the postcourse survey. Residents' self-rated level of preparedness increased for ACP discussions overall (4.0 pre vs. 5.2 post on 7-point Likert scale) and for communication steps involved in ACP (p < 0.001). Fifty-nine percent of participants completed the six-month follow-up survey. Residents' self-rated preparedness to engage in outpatient ACP discussions remained high (4.5 pre vs. 5.5 post at six months p < 0.001). Residents also reported increased use of ACP communication skills (p < 0.001) six months later.
The GOCARE curriculum provides an alternative model of communication training that can be integrated into residency training and improve residents' skills in outpatient ACP discussions.
The human red hair color (RHC) trait is caused by increased pheomelanin (red-yellow) and reduced eumelanin (black-brown) pigment in skin and hair due to diminished melanocortin 1 receptor (MC1R) ...function. In addition, individuals harboring the RHC trait are predisposed to melanoma development. While MC1R variants have been established as causative of RHC and are a well-defined risk factor for melanoma, it remains unclear mechanistically why decreased MC1R signaling alters pigmentation and increases melanoma susceptibility. Here, we use single-cell RNA sequencing (scRNA-seq) of melanocytes isolated from RHC mouse models to define a MC1R-inhibited Gene Signature (MiGS) comprising a large set of previously unidentified genes which may be implicated in melanogenesis and oncogenic transformation. We show that one of the candidate MiGS genes, TBX3, a well-known anti-senescence transcription factor implicated in melanoma progression, binds both E-box and T-box elements to regulate genes associated with melanogenesis and senescence bypass. Our results provide key insights into further mechanisms by which melanocytes with reduced MC1R signaling may regulate pigmentation and offer new candidates of study toward understanding how individuals with the RHC phenotype are predisposed to melanoma.
In this report, the microstructures of conventional white cast irons (WCI) and new metal matrix composites (MMC) are compared. In contrast to casting, the hot isostatic pressing (HIP) of powder ...mixtures offers more freedom to design specific properties like toughness and wear resistance. Both may be enhanced by a proper MMC composition. Experimental results are so convincing that special industrial applications appear to be feasible as well as cost-effective and some have been initiated. New MMC for high temperature wear, for corrosive environments and for cold forging tools are presented. It is shown how the cost of hard particles in MMC may be reduced by in situ transformation of ferroalloy particles.
A new austenitic steel alloyed with carbon
+
nitrogen is developed based on ab initio calculations of the electronic structure, which were carried out using the local density functional theory, and ...on experimental studies by means of conduction electron spin resonance. It is shown that alloying of CrMn austenite with carbon
+
nitrogen increases the concentration of conduction electrons and assists their more homogeneous spatial distribution, which results in short-range atomic ordering and, consequently, in a higher thermodynamic stability of iron-based face-centered cubic solid solutions. The developed CrMnCN steel is characterized by a yield and ultimate strength of 600 and 1000
MPa, respectively, in combination with an extremely high fracture energy. The notch-impact toughness exceeds 400
J. The resistance to impact wear is comparable with that of Hadfield steel. Corrosive properties are in some corrosive media similar to those of austenitic Cr18Ni10 steel. Possible applications of the developed steel are discussed.
Gastric diseases, including peptic ulcer disease and gastric cancer, are highly prevalent in human beings. Despite this, the cellular biology of the stomach remains poorly understood relative to ...other gastrointestinal organs such as the liver, intestine, and colon. In particular, little is known about the molecular basis of stomach development and the differentiation of gastric lineages. Although animal models are useful for studying gastric development, function, and disease, there are major structural and physiological differences in human stomachs that render these models insufficient. To look at gastric development, function, and disease in a human context, a model system of the human stomach is imperative. This review details how this was achieved through the directed differentiation of human pluripotent stem cells in a 3-dimensional environment into human gastric organoids (HGOs). Similar to previous work that has generated human intestine, colon, and lung tissue in vitro, HGOs were generated in vitro through a step-wise differentiation designed to mimic the temporal-spatial signaling dynamics that control stomach development in vivo. HGOs can be used for a variety of purposes, including genetic modeling, drug screening, and potentially even in future patient transplantation. Moreover, HGOs are well suited to study the development and interactions of nonepithelial cell types, such as endothelial, neuronal, and mesenchymal, which remain almost completely unstudied. This review discusses the basics of stomach morphology, function, and developmental pathways involved in generating HGOs. We also highlight important gaps in our understanding of how epithelial and mesenchymal interactions are essential for the development and overall function of the human stomach.
New Pioneers of Optogenetics in Neuroscience Somuncu, Ö Sezin; Berns, H Matthew; Sanchez, J Guillermo
Advances in experimental medicine and biology,
2020, Letnik:
1288
Journal Article
Recenzirano
Optogenetics have recently increased in popularity as tools to study behavior in response to the brain and how these trends relate back to a neuronal circuit. Additionally, the high demand for human ...cerebral tissue in research has led to the generation of a new model to investigate human brain development and disease. Human Pluripotent Stem Cells (hPSCs) have been previously used to recapitulate the development of several tissues such as intestine, stomach and liver and to model disease in a human context, recently new improvements have been made in the field of hPSC-derived brain organoids to better understand overall brain development but more specifically, to mimic inter-neuronal communication. This review aims to highlight the recent advances in these two separate approaches of brain research and to emphasize the need for overlap. These two novel approaches would combine the study of behavior along with the specific circuits required to produce the signals causing such behavior. This review is focused on the current state of the field, as well as the development of novel optogenetic technologies and their potential for current scientific study and potential therapeutic use.
AbstractContextHigh quality advance care planning (ACP) discussions are important to ensure patient receipt of goal-concordant care, however there is no existing tool for assessing ACP communication ...quality. ObjectivesTo develop and validate a novel instrument that can be used to assess ACP communication skills of clinicians and trainees. MethodsWe developed a 20-item ACP Communication Assessment Tool (ACP-CAT) plus two summative items. Randomized rater pairs assessed residents’ performances in video-recorded standardized patient encounters before and after an ACP training program using the ACP-CAT. We tested the tool for its 1) discriminating ability, 2) interrater reliability 3) concurrent validity, 4) feasibility, and 5) raters’ satisfaction. ResultsFifty-eight pre/post-training video recordings from 29 first-year internal medicine residents at Mount Sinai Hospital were evaluated. ACP-CAT reliably discriminated performance pre- and post-training (median score 6 vs. 11, P < 0.001). For both pre/post-training encounters, interrater reliability was high for ACP-CAT total scores (intraclass correlation coefficient or ICC = 0.83 and 0.82) and the summative items Overall impression of ACP communication skills (ICC = 0.73 and 0.80) and Overall ability to respond to emotion (ICC = 0.83 and 0.82). Concurrent validity was shown by the strong correlation between ACP-CAT total score and both summative items. Raters spent an average of 4.8 minutes to complete the ACP-CAT, found it feasible, and were satisfied with its use. ConclusionsACP-CAT provides a validated measure of ACP communication quality for assessing video-recorded encounters and can be further studied for its applicability with clinicians in different clinical contexts.
A new physical concept for alloying austenitic and martensitic steels with carbon
+
nitrogen is proposed based on studies of the electron structure, atomic distribution and thermodynamic stability. ...It is shown that the C
+
N-enhanced metallic character of interatomic bonds can be used for the development of high-strength corrosion-resistant steels of highest fracture energy. Mechanical and corrosive properties of the steels developed are discussed.
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