Microbiome modulators for atopic eczema: a systematic review of experimental and investigational therapeutics.

INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory cutaneous disease that arises due to dysregulation of the Th2 immune response, impaired skin barrier integrity, and dysbiosis of the skin and gut microbiota. An abundance of Staphylococcus aureus biofilms in AD lesions increases the Th2 immune response, and gut bacteria release breakdown products such as Short Chain Fatty Acids that regulate the systemic immune response. AREAS COVERED: We aim to evaluate therapies that modulate the microbiome in humans and discuss the clinical implications of these treatments. We performed a review of the literature in which 2,673 records were screened, and describe the findings of 108 studies that were included after full-text review. All included studies discussed the effects of therapies on the human microbiome and AD severity. Oral probiotics, topical probiotics, biologics, and investigational therapies were included in our analysis. EXPERT OPINION: Oral probiotics demonstrate mixed efficacy at relieving AD symptoms. Topical probiotics reduce S. aureus abundance in AD lesional skin, yet for moderate-severe disease, these therapies may not reduce AD severity scores to the standard of biologics. Dupilumab and tralokinumab target key inflammatory pathways in AD and modulate the skin microbiome, further improving disease severity.

Impact of High School Quality on Academic Performance Throughout Medical School.

INTRODUCTION: Numerous studies currently evaluate medical school success and performance using college Grade Point Average (GPA) and Medical College Admissions Test (MCAT) scores. These studies demonstrate that students who score low on the MCAT will continually perform worse than their peers on medical school exams and board exams. We investigated where a student attended high school and how that factor can affect medical school performance because most studies evaluated performance based on college attendance. METHODS: Our retrospective study evaluated 184 students at Kirk Kerkorian School of Medicine (KSOM) and showed higher-quality high schools, in comparison to lower-quality high schools, affected medical school performance. We categorized two groups for high school quality based on the U.S. News scorecard for programs within Nevada: those students with a high school reading proficiency (HSRP) >50% and those with an HSRP <50%. These two groups were then standardized based on percentile within the school and averaged using HSRP, MCAT, pre-clinical, step 1, clinical, and step 2 scores. A line chart was graphed to demonstrate the difference between the two groups. DATA/RESULTS: As might be expected, our results showed significantly higher MCAT scores from students who attended high-quality versus low-quality high schools. Our results also showed that although students from low-quality high schools performed worse for the first part of medical school, by step 2, students will score similarly in both groups. CONCLUSION: Students who performed poorly on the MCAT and attended lower-quality high schools will score as competitively as their peers by step 2.

Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.

The development of 1,3,4,4a,5,10a-hexahydropyrano[3,4-b]chromene analogs as BACE1 inhibitors is described. Introduction of the spirocyclic pyranochromene scaffold yielded several advantages over previous generation cores, including increased potency, reduced efflux, and reduced CYP2D6 inhibition. Compound 13 (BACE1 IC50=110 nM) demonstrated a reduction in CSF Aß in wild type rats after a single dose.

Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: expansion of substrate scope and mechanistic studies.

Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.

Regioselective activation of glycosyl acceptors by a diarylborinic acid-derived catalyst.

A derivative of diphenylborinic acid promotes catalytic, regioselective Koenigs-Knorr glycosylations of carbohydrate derivatives bearing multiple secondary hydroxyl groups. Robust levels of selectivity for the equatorial OH group of cis-1,2-diol motifs are demonstrated in reactions of seven acceptors derived from galactose, mannose, fucose, and arabinose using a variety of glycosyl halide donors. Catalyst control presents a new means of generating defined glycosidic linkages from unprotected or minimally protected carbohydrate feedstocks.

Regioselective alkylation of carbohydrate derivatives catalyzed by a diarylborinic acid derivative.

Regioselective, catalyst-controlled monoalkylations of cis-vicinal diol motifs in carbohydrate derivatives, using a diphenylborinic ester precatalyst, are described. Selective installation of benzyl, naphthylmethyl, 4-bromobenzyl and benzyloxymethyl protective groups at a single secondary hydroxy group of ten representative carbohydrate derivatives illustrates the scope of this method. This new mode of catalytic reactivity represents an operationally simple method to access useful monoalkylated building blocks while avoiding the use of stoichiometric quantities of organotin reagents.

Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience.

BACKGROUND: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. METHODS: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n = 2), acute on chronic liver failure (n = 12), posthepatectomy liver failure (n = 4), and posttransplantation allograft failure (n = 4). RESULTS: MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P < 0.001 for all three parameters). Five patients (22.7%) were able to bridge to transplantation and one patient (4.5%) made a spontaneous recovery. The 30-day mortality rate was 72.7%. CONCLUSIONS: Our results indicated that MARS can effectively improve serum biochemistry and is suitable for temporarily supporting patients with liver failure where transplantation is not immediately available. There is, however, no clear evidence showing that MARS can increase survival, improve the chance of transplantation or assist liver regeneration. Future studies in the form of randomized-controlled trials are crucial to characterize the true potential of this treatment.