An efficient regioconvergent synthesis of 3-aza-obeticholic acid.

Bile acids (BAs) are steroidal molecules that play important roles in nutrient absorption, distribution, and excretion. They also act on specific receptors implicated in various metabolic and inflammatory diseases demonstrating their importance as potential drug candidates. Accordingly, there has been a concerted effort to develop new BA derivatives to probe structure-activity relationships with the goal of discovering BA analogues with enhanced pharmacological properties.

Nurses You Should Know: The power of online microlearning to decolonize nursing's history.

Black, Hispanic, Indigenous, Native American, Asian, and Pacific Islander nurses have played a critical role in shaping professional nursing and health care. Despite their contributions, the narrative of nursing's origin has predominantly revolved around the legacy of a single white British nurse, Florence Nightingale. This paper presents the development of the Nurses You Should Know (NYSK) project, which sought to decolonize the narrative surrounding nursing's history and highlight the contributions and experiences of past and present-day nurses of color.

Software BreastAnalyser for the semi-automatic analysis of breast cancer immunohistochemical images.

Breast cancer is the most diagnosed cancer worldwide and represents the fifth cause of cancer mortality globally. It is a highly heterogeneous disease, that comprises various molecular subtypes, often diagnosed by immunohistochemistry. This technique is widely employed in basic, translational and pathological anatomy research, where it can support the oncological diagnosis, therapeutic decisions and biomarker discovery.

"I had become fed up": A qualitative study of Black nurse practitioners' experiences fighting against health inequity, racism, and burnout.

Background: Increasing diversity in the nurse practitioner (NP) workforce is key to improving outcomes among patients who experience health inequities. However, few studies to date have examined the specific mechanisms by which NPs from diverse backgrounds address inequities in care delivery.

Purpose: To explore Black NPs' efforts in addressing inequities, and the facilitators and barriers they face in doing so.

Perspectives and corrective processes: Evaluating social justice in a nursing PhD program.

Efforts to integrate tenets of social justice into PhD nursing programs are long-standing but have intensified in the past few years in response to civil unrest, threats to human rights, and health inequities exacerbated during the COVID-19 pandemic. In this paper, we present an overview of our School of Nursing's efforts and processes to evaluate and ensure that social justice principles were reflected throughout the PhD program. Components of this initiative included (a) forming a Social Justice Taskforce, (b) conducting listening sessions with alumni and currently enrolled PhD students to understand student experiences, (c) surveying PhD students to aid in prioritization of recommendations for improvement, and (d) convening key stakeholders to connect student priority areas to institutional programs and practices.

Inhibition profile of trifludimoxazin towards PPO2 target site mutations.

Background: Target site resistance to herbicides that inhibit protoporphyrinogen IX oxidase (PPO; EC 1.3.3.

HIV and Substance Use in Latin America: A Scoping Review.

This scoping review aims to explore the interplay between substance use (SU) and HIV in Latin America (LA). Database searches yielded 3481 references; 196 were included. HIV prevalence among people who used substances (PWUS) ranged from 2.

A Novel Single-Site Mutation in the Catalytic Domain of Protoporphyrinogen Oxidase IX (PPO) Confers Resistance to PPO-Inhibiting Herbicides.

Protoporphyrinogen oxidase (PPO)-inhibiting herbicides are used to control weeds in a variety of crops. These herbicides inhibit heme and photosynthesis in plants. PPO-inhibiting herbicides are used to control (Palmer amaranth) especially those with resistance to glyphosate and acetolactate synthase (ALS) inhibiting herbicides.

Barriers to Care for Persons With Sickle Cell Disease: The Case Manager's Opportunity to Improve Patient Outcomes.

Purpose And Objectives: The purpose of this discussion is to review the barriers to care for patients with sickle cell disease (SCD). Chronic pain and the perception of addiction, implicit bias, frequent hospitalizations and emergency department visits, clinician and patient knowledge deficits, and SCD stigma all impede the ability to provide evidence-based care for patients with SCD. Case managers can coordinate and advocate for appropriate care that improves patient outcomes.

Potent Inhibitors of Plasmodial Serine Hydroxymethyltransferase (SHMT) Featuring a Spirocyclic Scaffold.

With the discovery that serine hydroxymethyltransferase (SHMT) is a druggable target for antimalarials, the aim of this study was to design novel inhibitors of this key enzyme in the folate biosynthesis cycle. Herein, 19 novel spirocyclic ligands based on either 2-indolinone or dihydroindene scaffolds and featuring a pyrazolopyran core are reported. Strong target affinities for Plasmodium falciparum (Pf) SHMT (14-76 nm) and cellular potencies in the low nanomolar range (165-334 nm) were measured together with interesting selectivity against human cytosolic SHMT1 (hSHMT1).

Multiple mechanisms are involved in new imazamox-resistant varieties of durum and soft wheat.

Weed control in wheat is one of the major goals of farmers in their efforts toward obtaining the highest crop yields for human foods. Several studies (dose-response, enzyme activity, absorption-translocation and metabolism) were conducted to characterize the resistance level of two new wheat cultivars called Rafalín (Triticum aestivum) and Antoñín (T. durum) that were obtained by conventional breeding based on Clearfield® technology; they are resistant (R) to imazamox compared to their sensitive (S) counterparts (Gazul and Simeto, respectively).

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated.

Conformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifs.

Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18-56 nm).

Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures.

Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.

STR allele sequence variation: Current knowledge and future issues.

This article reviews what is currently known about short tandem repeat (STR) allelic sequence variation in and around the twenty-four loci most commonly used throughout the world to perform forensic DNA investigations. These STR loci include D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, SE33, D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E, D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045. All known reported variant alleles are compiled along with genomic information available from GenBank, dbSNP, and the 1000 Genomes Project.

Dealing with death: medical students' experiences with patient loss.

This article explores medical students' experiences and coping strategies when confronting patient loss in their 3rd and 4th years of their programs. Much of the literature on the impact of patient losses focuses on physicians. This article joins a handful of works aimed at how medical students experience and cope with patient loss.

Fine tuning of a biological machine: DnaK gains improved chaperone activity by altered allosteric communication and substrate binding.

DnaK is a member of the Hsp70 family of molecular chaperones. This molecular machine couples the binding and hydrolysis of ATP to binding and release of substrate proteins. The switches that are involved in allosteric communication within this multidomain protein are mostly unknown.

Directed evolution of the DnaK chaperone: mutations in the lid domain result in enhanced chaperone activity.

We improved the DnaK molecular chaperone system for increased folding efficiency towards two target proteins, by using a multi-parameter screening procedure. First, we used a folding-deficient C-terminal truncated chloramphenicol acetyl transferase (CAT_Cd9) to obtain tunable selective pressure for enhanced DnaK chaperon function in vivo. Second, we screened selected clones in vitro for CAT_Cd9 activity after growth under selective pressure.

Migraine with unilateral motor symptoms: a case-control study.

Objective: To characterise the clinical features of non-familial migraine with unilateral motor symptoms (MUMS) and compare these features with those of migraine without weakness.

Methods: 24 patients with MUMS and 48 matched controls were identified from a tertiary care headache centre. Using a structured interview, the migraine symptoms of both groups were characterised.

Biochemical characterization of prephenate dehydrogenase from the hyperthermophilic bacterium Aquifex aeolicus.

A monofunctional prephenate dehydrogenase (PD) from Aquifex aeolicus was expressed as a His-tagged protein in Escherichia coli and was purified by nickel affinity chromatography allowing the first biochemical and biophysical characterization of a thermostable PD. A. aeolicus PD is susceptible to proteolysis.

Endoscopic access to the extremities: the principle of fascial clefts.

Technology for endoscopic surgery has developed rapidly during the last decade. Applications of endoscopic techniques to orthopaedic surgery have been made possible by the use of balloon dissectors. Balloon dissectors create an optical cavity by separating fascial layers of a constant anatomic plane called the fascial cleft.

Expression, purification, and characterization of recombinant purine nucleoside phosphorylase from Escherichia coli.

Recombinant purine nucleoside phosphorylase (PNPase) from Escherichia coli was prepared in high yield in order to facilitate its use in coupled assays to measure the kinetics of phosphate-liberating enzymes. The E. coli enzyme was overexpressed in E.

Joint vibration analysis protocol modification: adding mandibular excursive movements.

This case study discusses the advantage of using both lateral and protrusive mandibular excursive movements to improve the accuracy of the joint vibration analysis rather than relying only on opening and closing movements of the mandible for analysis.

Use of the balloon dissector in minimally invasive aesthetic and reconstructive surgery.

The use of minimally invasive surgery continues to evolve in all fields of surgery with new developments in techniques and instrumentation. One instrument that has evolved and become useful in the field of plastic surgery is the balloon dissector. The purpose of this paper is to examine the role of the balloon dissector in minimally invasive aesthetic and reconstructive plastic surgery.