Integrating continuous flow reaction and work-up: chiral amine resolution, separation and purification using a novel coalescing filter system.

To maximize the benefits of a continuous flow reaction, a continuous work-up is also needed. Herein, we present a process design and novel equipment for a continuous amine resolution reaction, integrated with liquid-liquid (L-L) extraction, back-extraction into a different solvent, and crystallisation purification for product isolation. The reaction, in iso-propyl acetate, flows through a heated fixed-bed reactor with solid supported lipase which catalyses the resolution of ()-1-phenylethylamine to give the ()-amide in 50% conversion and 96% enantiomeric excess (ee).

Limiting pre-menstrual endometrial Hypoxia Inducible Factor 2 Alpha may fine-tune endometrial function at menstruation.

Context: Heavy menstrual bleeding (HMB) is common and debilitating, but the precise endometrial mechanisms causing increased menstrual blood loss (MBL) remain undefined. We have previously identified a role for hypoxia in endometrial repair following progesterone withdrawal.

Objective: As hypoxia inducible factor 2 alpha (HIF2A) is known to alter vascular function in other tissues, we hypothesised that endometrial HIF2A is involved in pre-menstrual optimisation of endometrial function during the secretory phase to limit MBL.

Electroreduction of CO to 2.8 A cm⁻ C Products: Maximizing Efficiency with Minimalist Electrode Design Featuring a Mesopore-Rich Hydrophobic Copper Catalyst Layer.

This work shows how hydrophobicity and porosity can be incorporated into copper catalyst layers (CLs) for the efficient electroreduction of CO (CORR) in a flow cell. Oxide-derived (OD) Cu catalysts are synthesized using K and Cs as templates, termed respectively as OD-Cu-K and OD-Cu-Cs. CLs, assembled from OD-Cu-K and OD-Cu-Cs, exhibit enhanced CORR performance compared to "unmodified" OD-Cu CL.

COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.

The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood.

On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids.

Triarylsilanols have been reported as the first silicon-centered molecular catalysts for direct amidation of carboxylic acids with amines as identified after a screen of silanols, silanediols, disiloxanediols, and incompletely condensed silsesquioxanes as potential homogeneous catalysts. Subsequent synthesis and testing of various electronically differentiated triarylsilanols have identified tris(-haloaryl)silanols as more active than the parent triarylsilanol, where the bromide congener is found to be the most active. Catalyst decomposition can be observed by NMR methods, but RPKA methods reveal that product inhibition is operative, where tertiary amides are more inhibitory than secondary amides.

Identification of ligand linkage vectors for the development of p300/CBP degraders.

To develop new degrader molecules from an existing protein ligand a linkage vector must be identified and then joined with a suitable E3 ligase without disrupting binding to the respective targets. This is typically achieved through empirically evaluating the degradation efficacy of a series of synthetic degraders. Our strategy for determining optimal linkage sites utilises biotinylated protein ligands, linked potential conjugation sites of an inhibitor to confirm whether target protein is maintained after forming a conjugate.

Regioselective Synthesis of C3-Hydroxyarylated Pyrazoles.

Pyrazoles are ubiquitous structures in medicinal chemistry. We report the first regioselective route to C3-hydroxyarylated pyrazoles obtained through reaction of pyrazole -oxides with arynes using mild conditions. Importantly, this method does not require the C4 and C5 positions of the pyrazole to be functionalized to observe regioselectivity.

Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries.

Current methods for the preparation of heterobifunctional pomalidomide-conjugates rely on methods that are often low yielding and produce intractable byproducts. Herein we describe our strategy for the reliable and succinct preparation of pomalidomide-linkers which is essential to the formation of these conjugates. We present the preparation of 18 pomalidomide-linkers in high yield compared to current literature methods.

Tetramethyl Orthosilicate (TMOS) as a Reagent for Direct Amidation of Carboxylic Acids.

Tetramethyl orthosilicate (TMOS) is shown to be an effective reagent for direct amidation of aliphatic and aromatic carboxylic acids with amines and anilines. The amide products are obtained in good to quantitative yields in pure form directly after workup without the need for any further purification. A silyl ester as the putative activated intermediate is observed by NMR methods.

Long-term health effects among testicular cancer survivors.

Purpose: Testicular cancer is diagnosed at a young age and survival rates are high; thus, the long-term effects of cancer treatment need to be assessed. Our objectives are to estimate the incidence rates and determinants of late effects in testicular cancer survivors.

Methods: We conducted a population-based cohort study of testicular cancer survivors, diagnosed 1991-2007, followed up for a median of 10 years.

Ten years of recreational diving fatalities in the United States and Canada: harvesters vs non-harvesters.

Adult male recreational diver fatalities (n = 698) in North America from 2004 to 2013 were examined. Compared with non-harvesters, boat (86 vs 59%), solo (26 vs 13%) and night diving (10 vs 3%) were more common among harvesters. Of the divers who were low-on or out-of air, 20% were harvesters and 11% non-harvesters (OR = 2.

Initial Outcomes of a Lung Cancer Screening Program in an Integrated Community Health System.

Purpose: Lung cancer screening with low-dose CT (LDCT) demonstrated reduced mortality in the National Lung Screening Trial, yet there is debate as to whether the reported efficacy can translate into comparable effectiveness with community-based screening. The authors' purpose is to report the baseline patient characteristics and malignancy rate in the first 18 months after implementing a lung cancer screening program in an integrated community health system.

Methods: Patients were screened at 1 of 10 participating community-based centers within a 22-hospital system from 2013 to 2015.

Use of posttreatment imaging and biomarkers in survivors of early-stage breast cancer: Inappropriate surveillance or necessary care?

Background: Advanced imaging and serum biomarkers are commonly used for surveillance in patients with early-stage breast cancer, despite recommendations against this practice. Incentives to perform such low-value testing may be less prominent in integrated health care delivery systems. The purpose of the current study was to evaluate and compare the use of these services within 2 integrated systems: Kaiser Permanente (KP) and Intermountain Healthcare (IH).

Use of imaging for staging of early-stage breast cancer in two integrated health care systems: adherence with a choosing wisely recommendation.

Purpose: Advanced imaging is commonly used for staging of early-stage breast cancer, despite recommendations against this practice. The objective of this study was to evaluate and compare use of imaging for staging of breast cancer in two integrated health care systems, Kaiser Permanente (KP) and Intermountain Healthcare (IH). We also sought to distinguish whether imaging was routine or used for diagnostic purposes.

Sexually explicit racialised media targeting men who have sex with men online: a content analysis of high-risk behaviour depicted in online advertisements.

Sexually explicit media may perpetuate racial and sexual norms among men who have sex with men. While men may be exposed to sexually explicit media in the online settings where they seek sex with other men, no studies to our knowledge have explored the relationship between the racial and sexual content of advertisements appearing in these spaces. In 2011, using a detailed codebook, 217 sexually explicit advertisements on a male sex-seeking website were coded for themes, actor characteristics and sexual acts depicted.

Perioperative Warming in Surgical Patients: A Comparison of Interventions.

The four arm study investigates how use of a preoperative forced-air warming blanket and adjustment of ambient surgical room temperature may contribute to prevention of perioperative hypothermia. Active warming interventions may prevent the drop in core temperature that occur as a result of surgical anesthesia. Core body temperatures from a convenience sample of 220 adult surgical patients were sequentially monitored in the preoperative, intraoperative, and post-anesthesia care units (PACU) while receiving: (a) routine surgical care, (b) application of preoperative forced-air warming blanket, (c) application of preoperative forced-air warming blanket with adjustment of ambient surgical room temperatures, or (d) adjustment of ambient surgical room temperature only.

Adjuvant radiation in early stage, unfavorable histology endometrial carcinoma is associated with improved local control and survival.

Objective: Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods: We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011.

BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models.

Because of the complexity derived from the existence of various phosphoinositide 3-kinase (PI3K) isoforms and their differential roles in cancers, development of PI3K inhibitors with differential pharmacologic and pharmacokinetic profiles would allow best exploration in different indications, combinations, and dosing regimens. Here, we report BAY 80-6946, a highly selective and potent pan-class I PI3K inhibitor with sub-nanomolar IC50s against PI3Kα and PI3Kδ. BAY 80-6946 exhibited preferential inhibition (about 10-fold) of AKT phosphorylation by PI3Kα compared with PI3Kβ in cells.

Establishing the psychometric properties and preferences for the Northern Pain Scale.

Objectives: A culturally relevant, evidence-based pain assessment scale in Inuktitut is needed. Psychometric properties and preferences for the Northern Pain Scale (NorthPS), a revised version of the Wong-Baker FACES scale, were examined.

Study Design: This repeated-measures, within-subjects study involved 2 face-to-face interviews held 2 weeks apart.

Effects of varying gene targeting parameters on processing of recombination intermediates by ERCC1-XPF.

The ERCC1-XPF structure-specific endonuclease is necessary for correct processing of homologous recombination intermediates requiring the removal of end-blocking nonhomologies. We previously showed that targeting the endogenous CHO APRT locus with plasmids designed to generate such intermediates revealed defective recombination phenotypes in ERCC1 deficient cells, including suppression of targeted insertion and vector correction recombinants and the generation of a novel class of aberrant recombinants through a deletogenic mechanism. In the present study, we examined some of the mechanistic features of ERCC1-XPF in processing recombination intermediates by varying gene targeting parameters.

Coexposure to mercury increases immunotoxicity of trichloroethylene.

We have shown previously that chronic (32 weeks) exposure to occupationally relevant concentrations of the environmental pollutant trichloroethylene (TCE) induced autoimmune hepatitis (AIH) in autoimmune-prone MRL+/+ mice. In real-life, individuals are never exposed to only one chemical such as TCE. However, very little is known about the effects of chemical mixtures on the immune system.

Variable specimen handling affects hormone receptor test results in women with breast cancer: a large multihospital retrospective study.

Context: Intermountain Healthcare hospitals use a single, standardized laboratory and automated testing process for estrogen receptor/progesterone receptor (ER/PR) tests to minimize testing errors.

Objectives: To test the (1) variability in ER/PR negativity among hospitals and (2) association between specimen handling conditions and ER/PR negativity.

Design: Retrospective study of women who had breast cancer surgery at 7 Intermountain hospitals and ER/PR tests ordered between 1997 and 2003.

Detection of baseline and near-fall postural stability.

It is unknown whether there are any measurable warning signs just before a patient falls. This study of postural position just prior to a fall involved a subject standing on a balance beam while wearing a gyroscope-based wireless data acquisition system. Results show a variation in postural position when the subject appeared stable.