Copper-Catalyzed Diastereo-, Enantio-, and ()-Selective Aminoallylation of Ketones through Reductive Couplings of Azatrienes for the Synthesis of Allylic 1,2-Amino Tertiary Alcohols.

We introduce a method for the ()-selective aminoallylation of a range of ketones to prepare allylic 1,2-amino tertiary alcohols with excellent diastereo- and enantioselectivity. Copper-catalyzed reductive couplings of 2-azatrienes with aryl/alkyl and dialkyl ketones proceed with Ph-BPE as the supporting ligand, generating -amino alcohols with >98% ()-selectivity under mild conditions. The utility of the products is highlighted through several transformations, including those that leverage the ()-allylic amine moiety for diastereoselective reactions of the alkene.

Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli.

Introduction: Chronic itch is a central symptom of atopic dermatitis. Cutaneous afferent neurons express receptors interleukins (IL)-4, IL-13, and IL-33, which are type 2 cytokines that are elevated in atopic dermatitis. These neuronal cytokine receptors were found to be required in several murine models of itch.

Changing protein-DNA interactions promote ORC binding-site exchange during replication origin licensing.

During origin licensing, the eukaryotic replicative helicase Mcm2-7 forms head-to-head double hexamers to prime origins for bidirectional replication. Recent single-molecule and structural studies revealed that one molecule of the helicase loader ORC (origin recognition complex) can sequentially load two Mcm2-7 hexamers to ensure proper head-to-head helicase alignment. To perform this task, ORC must release from its initial high-affinity DNA-binding site and "flip" to bind a weaker, inverted DNA site.

Changing protein-DNA interactions promote ORC binding site exchange during replication origin licensing.

Unlabelled: During origin licensing, the eukaryotic replicative helicase Mcm2-7 forms head-to-head double hexamers to prime origins for bidirectional replication. Recent single-molecule and structural studies revealed that one molecule of the helicase loader ORC can sequentially load two Mcm2-7 hexamers to ensure proper head-to-head helicase alignment. To perform this task, ORC must release from its initial high-affinity DNA binding site and "flip" to bind a weaker, inverted DNA site.

Dupilumab Provides Clinically Meaningful Responses in Children Aged 6-11 Years with Severe Atopic Dermatitis: Post Hoc Analysis Results from a Phase III Trial.

Background: Children with severe atopic dermatitis (AD) have a multidimensional disease burden.

Objective: Here we assess the clinically meaningful improvements in AD signs, symptoms, and quality of life (QoL) in children aged 6-11 years with severe AD treated with dupilumab compared with placebo.

Methods: R668-AD-1652 LIBERTY AD PEDS was a randomized, double-blinded, placebo-controlled, parallel-group, phase III clinical trial of dupilumab with concomitant topical corticosteroids (TCS) in children aged 6-11 years with severe AD.

Survival in elderly patients with breast cancer with and without autoimmune disease.

Background: Patients with certain autoimmune conditions are at a reduced risk of developing breast cancer compared to the general population. Despite this, little is known about outcomes in patients with breast cancer who have a concurrent autoimmune diagnosis.

Methods: This study compared differences in outcomes between women with breast cancer who had or did not have an autoimmune diagnosis.

NSCLC in the Era of Targeted and Immunotherapy: What Every Pulmonologist Must Know.

The treatment of non-small cell lung cancer has dramatically changed over the last decade through the use of targeted therapies and immunotherapies. Implementation of these treatment regimens relies on detailed knowledge regarding each tumor's specific genomic profile, underscoring the necessity of obtaining superior diagnostic tissue specimens. While these treatment approaches are commonly utilized in the metastatic setting, approval among earlier-stage disease will continue to rise, highlighting the importance of early and comprehensive biomarker testing at the time of diagnosis for all patients.

Comparing Survival in Patients With Lung Cancer With and Without a History of Common Autoimmune Disease.

Introduction: Autoimmune disease has both a predisposing and a protective effect toward malignancy. Though studies have investigated the risk of malignancy in patients with autoimmune disease, there is limited research on how autoimmunity affects survival.

Methods: This study compared survival in patients with lung cancer with and without autoimmune disease.

Differential Susceptibility of Retinal Neurons to the Loss of Mitochondrial Biogenesis Factor Nrf1.

The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates.

Dupilumab significantly improves skin barrier function in patients with moderate-to-severe atopic dermatitis.

Background: Atopic dermatitis (AD) is characterized by abnormal skin lipids that are largely driven by hyperactivated type 2 immune responses. The antibody to the α-subunit of interleukin (IL)-4 receptor, dupilumab, was recently approved to treat AD and demonstrated strong efficacy. However, the role of dupilumab therapy in the regulation of skin barrier structure and function has not been fully explored.

Effect of Inpatient Integrative Medicine Consultation on 30-Day Readmission Rates: A Retrospective Observational Study at a Major U.S. Academic Hospital.

The prevalence of inpatient integrative medicine (IM) consult services is increasing among academic health care institutions. The diversity of services between institutions, as well as the novel nature of such interventions, makes it challenging for health care administrators to determine the cost/benefit of adding such a program to their institution. The main purpose of this study was to examine the performance of the new University of California, Los Angeles (UCLA) East-West (EW) consult service as measured by 30-day readmission rates and lengths of stay.

Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis-A pooled analysis of trial data.

Background/objective: Patients with moderate-to-severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non-herpetic skin infections in adults with moderate-to-severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate-to-severe and severe AD participating in clinical trials.

Providing support in a pandemic: A medical student telehealth service for ambulatory patients with COVID-19.

During the early months of the COVID-19 pandemic, when health systems were overwhelmed with surging hospitalizations and a novel virus, many ambulatory patients diagnosed with COVID-19 lacked guidance and support as they convalesced at home. This case report offers insight into the implementation of a telehealth service utilizing third- and fourth-year medical students to provide follow-up to ambulatory patients diagnosed with COVID-19. The service was evaluated using medical student surveys and retrospective chart review to assess the clinical and social needs of patients during the spring of 2020.

Dupilumab Treatment Reduces Hospitalizations in Adults With Moderate-to-Severe Atopic Dermatitis.

Background: Refractory disease, flares, or infections in atopic dermatitis (AD) can lead to hospitalizations.

Objective: To compare hospitalization rates among adults with moderate-to-severe AD treated with dupilumab versus control.

Methods: Data from 7 randomized, placebo-controlled trials of dupilumab (300 mg every 2 weeks [q2w] and/or weekly [qw]; with or without topical corticosteroids) were analyzed.

Dupilumab with Topical Corticosteroids Provides Rapid and Sustained Improvement in Adults with Moderate-to-Severe Atopic Dermatitis Across Anatomic Regions Over 52 Weeks.

Introduction: In a 52-week, phase 3 clinical trial (LIBERTY AD CHRONOS) in adult patients with moderate-to-severe atopic dermatitis (AD), dupilumab in combination with topical corticosteroids (TCS) resulted in a significant improvement in overall Eczema Area and Severity Index (EASI) compared with placebo plus TCS. In a post hoc analysis, dupilumab significantly improved the overall extent and severity of AD across four anatomic regions (head and neck, trunk, upper extremities, lower extremities) over 16 weeks. However, as AD severity and presentation may vary by body region, this analysis sought to determine whether there are regional variations in dupilumab efficacy.

Learning at a social distance: A medical student telehealth service for COVID-19 patients.

This article was migrated. The article was marked as recommended. COVID-19 has disrupted traditional forms of clinical practice in both inpatient and outpatient settings.

Effects of Intensive Outpatient Integrative Medicine on Health Care Utilization on High Utilizer Patients at a Major Academic Health System.

To determine if integrative medicine (IM) involvement can reduce acute care utilization for patients with complex medical conditions and high health care utilization. Prospective single-center cohort study. Twenty-nine complex high utilizer patients were treated by the University of California, Los Angeles (UCLA) East-West Extensivist IM specialty clinic with acupuncture, trigger point injections, and Traditional Chinese Medicine dietary modifications.

Identifying airborne transmission as the dominant route for the spread of COVID-19.

Various mitigation measures have been implemented to fight the coronavirus disease 2019 (COVID-19) pandemic, including widely adopted social distancing and mandated face covering. However, assessing the effectiveness of those intervention practices hinges on the understanding of virus transmission, which remains uncertain. Here we show that airborne transmission is highly virulent and represents the dominant route to spread the disease.

Carbenium ion-mediated oligomerization of methylglyoxal for secondary organic aerosol formation.

Secondary organic aerosol (SOA) represents a major constituent of tropospheric fine particulate matter, with profound implications for human health and climate. However, the chemical mechanisms leading to SOA formation remain uncertain, and atmospheric models consistently underpredict the global SOA budget. Small α-dicarbonyls, such as methylglyoxal, are ubiquitous in the atmosphere because of their significant production from photooxidation of aromatic hydrocarbons from traffic and industrial sources as well as from biogenic isoprene.