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A thorough understanding of Multiple Sclerosis (MS) is necessary to offer individuals informed options for treatment and planning. To assist in this quest, the following historical analysis examined how MS has been conceived from the 14th century through the early 20th century. Primary sources were consulted whenever possible, and many of the original archival materials were accessed by the first author (MB) during an on-site visit to the Rare Book Room of the New York Academy of Medicine. There is a striking similarity between how MS symptoms have presented throughout history compared with the 21st century. Sensorimotor and cognitive sequelae have been observed in patients since the 1800s. Cognitive symptoms were acknowledged in the 1800s, but disregarded in the early 1900s and were not given recognition again until the latter part of the 20th century. If conceptualizations of MS are inaccurate, patients will not be served well. In contrast to the shared symptomatology across time, early conceptualizations of etiology and treatment choices differed dramatically from today, a genuine reflection of the times in which they were created.

Quality improvement training during residency is a crucial component of post-graduate medical education and is one of the Association of American Medical Colleges Cross-Continuum Competencies and the six Accreditation Council for Graduate Medical Education domains of clinical competency. No national standard curriculum exists when it comes to training emergency medicine residents. A novel residency-focused QI curriculum was implemented to help emergency medicine residents develop foundational skills in QI and to translate these skills into practical projects that span multiple disciplines. The curriculum was effective, is readily adaptable to the resident physician and medical student levels, and supports the national trend toward implementing education in QI earlier in physician training.

The melanocortin system plays a central role in regulating hunger and satiety, making it an attractive target for treating metabolic disease. However, the limited clinical success of selective melanocortin-4 receptor (MC4R) agonists prompted the investigation of whether concurrent melanocortin-3 receptor (MC3R) and MC4R activation is key to unlocking the melanocortin system for the treatment of general obesity. To test this hypothesis, we designed and synthesized novel peptides to probe the distinct and combined roles of MC3R and MC4R in nonhuman primates (NHPs). We show that selectively agonizing MC3R modulates food intake in a state-dependent manner. Moreover, co-agonism of MC3R and MC4R results in more substantial metabolic effects than selective MC4R agonism, highlighting both a non-redundant and a cooperative role of MC3R. To leverage these discoveries, we developed 710GO, an orally-available MC3R/MC4R dual agonist peptide that induces significant weight loss in diet-induced obese (DIO) NHPs. Oral 710GO treatment demonstrates limited weight rebound, has additive effects in combination with GLP-1s, and exhibits a clean safety profile. These results reestablish the melanocortin system, specifically concerted MC3R/MC4R agonism, as a viable mechanism for next-generation obesity therapeutics.Competing Interest StatementDLM is a consultant, chief medical officer, stockholder, and has received grant funding from Endevica Bio Inc. DLM has served as a consultant for Alkermes Inc. and Pfizer Inc. RP is the chief executive officer, stockholder, and chair of the board for Endevica Bio Inc. JLS, ACI, EZ, KJK, TLB, BS, CRP, BHR, BAB, and JYD are employees and stockholders in Endevica Bio Inc.Footnotes* Selective compounds in the main text were mislabeled on page 4 and have been corrected. Figure 4B updated to show non-normalized weight rebound. This change was made to allow for ease of comparison with other weight loss compounds.

An analysis outlines the attractiveness of corporate bonds as an asset class. Returns and default data are reviewed, and the results show that investors have been well rewarded for accepting corporate credit risk in the fixed-income market. Fixed-income investors should allow for a significant commitment to corporate bonds within certain constraints. Given the role that bonds traditionally play in investment portfolios, high overall credit quality and a high degree of diversification should be maintained. Yet investors should retain flexibility to include individual securities that are not themselves highly rated if they want to capitalize on the unique opportunities in the corporate sector. Balanced portfolios should allocate to the high-yield market. The hybrid debt-equity nature of high-yield corporate bonds makes their management a natural extension of balanced-account management. High-yield investment should be funded from a combination of fixed-income and equity monies in order to maintain the desired overall risk profile.

Developed from the original series The Brain, these flexible resources offer extensive footage and research into the inner workings of this amazing human organ, including findings on Alzheimer’s disease, schizophrenia, autism, Parkinson’s disease, and many other topics. The modules are appropriate for use in general and advanced courses in psychology, abnormal and physiological psychology, neuropsychology, and occupational therapy.

Developed from the original series The Brain, these flexible resources offer extensive footage and research into the inner workings of this amazing human organ, including findings on Alzheimer’s disease, schizophrenia, autism, Parkinson’s disease, and many other topics. The modules are appropriate for use in general and advanced courses in psychology, abnormal and physiological psychology, neuropsychology, and occupational therapy.

Developed from the original series The Brain, these flexible resources offer extensive footage and research into the inner workings of this amazing human organ, including findings on Alzheimer’s disease, schizophrenia, autism, Parkinson’s disease, and many other topics. The modules are appropriate for use in general and advanced courses in psychology, abnormal and physiological psychology, neuropsychology, and occupational therapy.

Developed from the original series The Brain, these flexible resources offer extensive footage and research into the inner workings of this amazing human organ, including findings on Alzheimer’s disease, schizophrenia, autism, Parkinson’s disease, and many other topics. The modules are appropriate for use in general and advanced courses in psychology, abnormal and physiological psychology, neuropsychology, and occupational therapy.

Developed from the original series The Brain, these flexible resources offer extensive footage and research into the inner workings of this amazing human organ, including findings on Alzheimer’s disease, schizophrenia, autism, Parkinson’s disease, and many other topics. The modules are appropriate for use in general and advanced courses in psychology, abnormal and physiological psychology, neuropsychology, and occupational therapy.

Developed from the original series The Brain, these flexible resources offer extensive footage and research into the inner workings of this amazing human organ, including findings on Alzheimer’s disease, schizophrenia, autism, Parkinson’s disease, and many other topics. The modules are appropriate for use in general and advanced courses in psychology, abnormal and physiological psychology, neuropsychology, and occupational therapy.