Improving oral absorption of a rapidly crystallizing parent drug using prodrug strategy: Comparison of phosphate versus glycine based prodrugs.

With an increasing number of Biopharmaceutical Classification System (BCS) II/IV pipeline compounds, solubilizing and supersaturating formulation strategies are becoming prevalent. Beyond formulation and solid form strategies, prodrugs are also employed to overcome solubility-limited absorption of poorly water-soluble compounds. Prodrugs can potentially yield supersaturated systems upon conversion to the parent drug intraluminally and thus enhance absorption.

Discovery of Potent Azetidine-Benzoxazole MerTK Inhibitors with Target Engagement.

Inhibition of the receptor tyrosine kinase MerTK by small molecules has the potential to augment the immune response to tumors. Potent, selective inhibitors with high levels of target engagement are needed to fully evaluate the potential use of MerTK inhibitors as cancer therapeutics. We report the discovery and optimization of a series of pyrazinamide-based type 1.

Psychosocial interventions for post-treatment haematological cancer survivors: An integrative review.

Purpose: To synthesize literature regarding the implementation and evaluation of psychosocial interventions designed to reduce distress in post-treatment haematological cancer survivors.

Methods: An integrative review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases searched were Medline, Cinahl, PsychInfo, WoS, and EMBASE, during November 2022.

Squeezing the quantum noise of a gravitational-wave detector below the standard quantum limit.

The Heisenberg uncertainty principle dictates that the position and momentum of an object cannot be simultaneously measured with arbitrary precision, giving rise to an apparent limitation known as the standard quantum limit (SQL). Gravitational-wave detectors use photons to continuously measure the positions of freely falling mirrors and so are affected by the SQL. We investigated the performance of the Laser Interferometer Gravitational-Wave Observatory (LIGO) after the experimental realization of frequency-dependent squeezing designed to surpass the SQL.

Discovery of A-910, a Highly Potent and Orally Bioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor.

TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of , a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign.

An Exploratory Mixed-Methods Analysis of Factors Contributing to Students' Perceptions of Inclusion in Introductory STEM Courses.

In this exploratory mixed-methods analysis of students' perceptions of inclusion in introductory STEM courses for STEM majors, we asked students to rate inclusion in their class and to provide an open-text explanation of their rating. Analyzing 1930 qualitative responses resulted in a codebook containing academic, identity, and nonspecific categories. The majority of responses (>80%) cited academic factors such as interactions between students and instructors or course elements and policies.

Rural unpaid caregivers' experiences in northern Aotearoa, New Zealand during the Covid-19 pandemic: A qualitative study.

Objective: Rural unpaid caregivers experience different opportunities and challenges than their urban counterparts. Our aim was to understand rural unpaid caregivers' experiences of challenges and opportunities during the Covid-19 pandemic in New Zealand.

Setting: Rural northern New Zealand during the Covid-19 pandemic.

Convergence of Age Differences in Risk Preference, Impulsivity, and Self-Control: A Multiverse Analysis.

Objectives: Numerous theories exist regarding age differences in risk preference and related constructs, yet many of them offer conflicting predictions and fail to consider convergence between measurement modalities or constructs. To pave the way for conceptual clarification and theoretical refinement, in this preregistered study we aimed to comprehensively examine age effects on risk preference, impulsivity, and self-control using different measurement modalities, and to assess their convergence.

Methods: We collected a large battery of self-report, informant report, behavioral, hormone, and neuroimaging measures from a cross-sectional sample of 148 (55% female) healthy human participants between 16 and 81 years (mean age = 46 years, standard deviation [SD] = 19).

Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy.

Modern electroconvulsive therapy (ECT) and the approval of nasal esketamine for clinical use have significantly improved the approach to treatment-resistant depression (TRD), which is defined as non-response to at least two different courses of antidepressants with verified adherence to treatment, adequate dosage, and duration of treatment. The goal of this literature review is to present the newest evidence regarding efficacy and safety. Furthermore, we aim to provide an overview of future perspectives in this field of research, for example, regarding structural and molecular effects.

Effects of Pregnancy Prevention on Brucella abortus Shedding in American bison (Bison bison).

Products of parturition are the predominant source of Brucella abortus for transmission in bison (Bison bison). Our objective was to assess whether preventing pregnancy in Brucella-seropositive bison reduced B. abortus shedding.

Effects of the Immunocontraceptive Gonacon on Pregnancy in Brucella-Seropositive American bison (Bison bison).

The purpose of this study was to determine if the number of pregnancies in naturally infected Brucella abortus-positive bison (Bison bison) cows would be reduced over a period of 5 yr after one treatment with 3000 µg gonadotropin-releasing hormone immunocontraceptive (GonaCon) compared to a similar group of naturally infected B. abortus-positive bison cows not treated with GonaCon. In each of the 5 yr, GonaCon-treated cows produced fewer offspring in relation to number of cows than the nontreated cows.

A Study Planning Exercise Associated with Decreased Distraction Levels among Introductory Biology Students.

Students struggle to regulate their learning during independent study sessions. In this study, we ask whether an online behavioral intervention helped introductory students decrease distraction while studying. The intervention consisted of exam 1 reflection, exam 2 planning, and exam 2 reflection exercises.

Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.

Background: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), in patients with treatment-resistant depression are unknown.

Methods: In an open-label, single-blind (with raters unaware of group assignments), multicenter, phase 3b, randomized, active-controlled trial, we assigned patients, in a 1:1 ratio, to receive flexible doses (according to the summary of product characteristics) of esketamine nasal spray (esketamine group) or extended-release quetiapine (quetiapine group), both in combination with an SSRI or SNRI.

Exploring the impact of e-learning modules and webinars on health professionals' understanding of the End of Life Choice Act 2019: a secondary analysis of Manatū Hauora - Ministry of Health workforce survey.

Aim: To explore the importance of health workforce training, particularly in newly regulated healthcare practices such as assisted dying (AD). This study aims to analyse the socio-demographic factors associated with health professionals' completion of the e-learning module and attendance at the two webinars provided by the New Zealand Ministry of Health - Manatū Hauora (MH) and whether completion of the e-learning module and webinars supported health professionals' understanding of the End of Life Choices Act 2019.

Method: Secondary analysis of the MH workforce surveys conducted in July 2021.

Exploring the Chemical Properties and Medicinal Applications of Tetramethylthiocycloheptyne Sulfoximine Used in Strain-Promoted Azide-Alkyne Cycloaddition Reactions.

The recently developed compound, tetramethylthiocycloheptyne sulfoximine (TMTHSI), has shown to be a promising strained alkyne for strain-promoted azide-alkyne cycloaddition (SPAAC), metal-free click chemistry. This research explores the properties of TMTHSI-based compounds via three aspects: (1) large-scale production, (2) unique stability in acidic conditions and its subsequent use in peptide synthesis, and (3) the functionalization of antibodies. Here, it is shown that (1) scale-up is achieved on a scale of up to 100 g.

Case report: Hyperactive delirium after a single dose of zolpidem administered additionally to psychopharmacotherapy including clozapine.

The non-benzodiazepine hypnotic zolpidem is frequently administered as a short term psychopharmacotherapy for insomnia. Although it is well-established in a broad clinical routine and often well-tolerated, severe delirium and complex sleep behavior were reported in rare cases. Hereby, it remains unclear whether zolpidem's potential for delirium might be enhanced when combined with further psychopharmacotherapeutics.

Psychosocial well-being in Long-Term Care in the Wake of COVID-19: Findings from a Qualitative Study in New Zealand.

Drawing on Mason Durie's (1985) New Zealand Whare Tapa Whā model of health (spiritual, emotional, physical, and family domains), the goal was to link a model of well-being with the lived reality for long-term care residents and bereaved family members during COVID-19. Interviews were conducted with five residents and six family members of previous residents of one long-term care in one urban centre between July and September 2020. The increased demands imposed by the pandemic highlighted the gaps in well-being for residents and families.

Case report: Interstitial pneumonitis after initiation of lamotrigine.

The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis.

AI aided workflow for hip dysplasia screening using ultrasound in primary care clinics.

Developmental dysplasia of the hip (DDH) is a common cause of premature osteoarthritis. This osteoarthritis can be prevented if DDH is detected by ultrasound and treated in infancy, but universal DDH screening is generally not cost-effective due to the need for experts to perform the scans. The purpose of our study was to evaluate the feasibility of having non-expert primary care clinic staff perform DDH ultrasound using handheld ultrasound with artificial intelligence (AI) decision support.

Health professionals' understanding and attitude towards the End of Life Choice Act 2019: a secondary analysis of Manatū Hauora - Ministry of Health workforce surveys.

Aim: To determine socio-demographic factors associated with health professionals' understanding of the End of Life Choice Act (the Act), support for assisted dying (AD), and willingness to provide AD in New Zealand.

Method: Secondary analysis of two Manatū Hauora - Ministry of Health workforce surveys conducted in February and July 2021.

Results: Our analysis showed (1) older health professionals (age>55) had a better overall understanding of the Act than their young colleagues (age⁢35), (2) female health professionals were less likely to support and be willing to provide AD, (3) Asian health professionals were less likely to support AD compared to their Pākehā/European counterparts, (4) nurses were more likely to support AD and be willing to provide AD when compared to medical practitioners, and (5) pharmacists were more willing to provide AD when compared to medical practitioners.

The challenges for health professionals delivering palliative care in the community during the COVID-19 pandemic: An integrative review.

Objectives: The growing demand for palliative care has been accelerated due to the COVID-19 pandemic. However, providing community-based palliative care was also more difficult to do safely and faced several challenges. The goal of this integrative review was to identify, describe, and synthesize previous studies on the challenges for health professionals delivering palliative care in the community during the COVID-19 pandemic.

Comparison of etomidate and methohexital as anesthetic agents for continuation and maintenance electroconvulsive therapy: A retrospective analysis of seizure quality and safety.

Background: The ideal hypnotic agent for electroconvulsive therapy (ECT) is still under debate and previous studies comparing etomidate and methohexital have produced conflicting results. This retrospective study compares etomidate and methohexital as anesthetic agents in continuation and maintenance (m)ECT with regard to seizure quality and anesthetic outcomes.

Methods: All subjects undergoing mECT at our department between October 1st, 2014 and February 28th, 2022 were included in this retrospective analysis.