BMAL1 controls glucose uptake through paired-homeodomain transcription factor 4 in differentiated Caco-2 cells.

The transcription factor aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) is an essential regulator of the circadian clock, which controls the 24-h cycle of physiological processes such as nutrient absorption. To examine the role of BMAL1 in small intestinal glucose absorption, we used differentiated human colon adenocarcinoma cells (Caco-2 cells). Here, we show that BMAL1 regulates glucose uptake in differentiated Caco-2 cells and that this process is dependent on the glucose transporter sodium-glucose cotransporter 1 (SGLT1). Mechanistic studies show that BMAL1 regulates glucose uptake by controlling the transcription of SGLT1 involving paired-homeodomain transcription factor 4 (PAX4), a transcriptional repressor. This is supported by the observation that clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated endonuclease Cas9 (Cas9) knockdown of PAX4 increases SGLT1 and glucose uptake. Chromatin immunoprecipitation (ChIP) and ChIP-quantitative PCR assays show that the knockdown or overexpression of BMAL1 decreases or increases the binding of PAX4 to the hepatocyte nuclear factor 1-α binding site of the SGLT1 promoter, respectively. These findings identify BMAL1 as a critical mediator of small intestine carbohydrate absorption and SGLT1.

Hypervalent iodine reactions utilized in carbon-carbon bond formations.

Advances in hypervalent iodine chemistry have put the field on the precipice of a second golden age; the first being pioneered in the 1990s. During that period, C-C bond forming reactions would be published but rarely with the intended goal of developing a C-C bond forming methodology. More recently, the development of hypervalent iodine-guided electrophilic substitution, arylations using hypervalent iodine, and photoredox reactions with hypervalent iodine have shown great progress in the area of C-C bond formation.

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups.

The reactivity of benzyl hypervalent iodine intermediates was explored in congruence with the reductive iodonio-Claisen rearrangement (RICR) to show that there may be an underlying mechanism which expands the reasoning behind the previously known C-C bond-forming reaction. By rationalizing the hypervalent iodine's metal-like properties it was concluded that a transmetallation mechanism could be occurring with metalloid groups such as silicon and boron. Hypervalent iodine reagents such as Zefirov's reagent, cyclic iodonium reagents, iodosobenzene/BF3, and PhI(OAc)2/BF3 or triflate-based activators were tested. A desirable facet of the reported reaction is that iodine(I) is incorporated into the product thus providing greater atom economy and a valuable functional group handle for further transformations. The altering of the RICR's ortho-selectivity to form para-selective products with benzyl hypervalent iodine intermediates suggests a mechanism that involves hypervalent iodine-guided electrophilic substitution (HIGES).

Expanding Medical Student Knowledge and Impacting Patient Outcomes Through a Student-Run Clinic: A Case-Based Reflection.

Cryptogenic stroke is a debilitating condition that requires follow-up care and treatment that is appropriate for the underlying etiology. Here, we present the case of a 46-year-old uninsured patient with an undocumented immigration status who presented to our student-run clinic (SRC) for the management of her post-stroke care. She initially presented to an outside hospital with focal neurological deficits, was diagnosed with an acute stroke, and was told to follow up with a primary care provider. The patient established care at the Cooper Medical School of Rowan University's SRC one week following her stroke event. The SRC served as a conduit for access to healthcare services necessary for her recovery and secondary prevention of future strokes which otherwise would have been unattainable due to the patient's socioeconomic constraints. These services and treatments included specialist appointments, anticoagulation medications, physical and speech therapy, labs, placement of an internal heart rhythm monitor, and surgical closure of a patent foramen ovale. All services, medications, and procedures were provided free of charge. One year following her stroke, the patient is living without disability and has had no recurrence of a cerebrovascular ischemic event. This case highlights the dual-purposed value of SRCs in providing both meaningful clinical educational experiences to students and necessary health care to disadvantaged patients.

Measures of Emergency Department Crowding, a Systematic Review. How to Make Sense of a Long List.

Emergency department (ED) crowding, a common and serious phenomenon in many countries, lacks standardized definition and measurement methods. This systematic review critically analyzes the most commonly studied ED crowding measures. We followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We searched PubMed/Medline Database for all studies published in English from January 1st, 1990, until December 1st, 2020. We used the National Institute of Health (NIH) Quality Assessment Tool to grade the included studies. The initial search yielded 2293 titles and abstracts, of whom we thoroughly reviewed 109 studies, then, after adding seven additional, included 90 in the final analysis. We excluded simple surveys, reviews, opinions, case reports, and letters to the editors. We included relevant papers published in English from 1990 to 2020. We did not grade any study as poor and graded 18 as fair and 72 as good. Most studies were conducted in the USA. The most studied crowding measures were the ED occupancy, the ED length of stay, and the ED volume. The most heterogeneous crowding measures were the boarding time and number of boarders. Except for the National ED Overcrowding Scale (NEDOCS) and the Emergency Department Work Index (EDWIN) scores, the studied measures are easy to calculate and communicate. Quality of care was the most studied outcome. The EDWIN and NEDOCS had no studies with the outcome mortality. The ED length of stay had no studies with the outcome perception of care. ED crowding was often associated with worse outcomes: higher mortality in 45% of the studies, worse quality of care in 75%, and a worse perception of care in 100%. The ED occupancy, ED volume, and ED length of stay are easy to measure, calculate and communicate, are homogenous in their definition, and were the most studied measures.