Vitamin B12 Deficiency in Children and Adolescents: A Case for Revised Diagnostic Parameters.

Background: Vitamin B12 deficiency is commonly diagnosed using thresholds developed for adults, yet emerging evidence indicates these levels may not be appropriate for children and adolescents. This misalignment can lead to underdiagnosis in younger populations, with potential long-term health implications.

Case Summary: Chief Complaint: The 17-year-old female patient experienced severe fatigue, menstrual irregularities, psychological distress, and neurological symptoms over several years.

Improving Practice for Urinary Continence Care on Adult Acute Medical and Rehabilitation Wards: A Multi-Site, Co-Created Implementation Study.

Many adult inpatients experience urinary continence issues; however, we lack evidence on effective interventions for inpatient continence care. We conducted a before and after implementation study. We implemented our guideline-based intervention using strategies targeting identified barriers and evaluated the impact on urinary continence care provided by inpatient clinicians.

AZD0284, a Potent, Selective, and Orally Bioavailable Inverse Agonist of Retinoic Acid Receptor-Related Orphan Receptor C2.

Inverse agonists of the nuclear receptor RORC2 have been widely pursued as a potential treatment for a variety of autoimmune diseases. We have discovered a novel series of isoindoline-based inverse agonists of the nuclear receptor RORC2, derived from our recently disclosed RORC2 inverse agonist . Extensive structure-activity relationship (SAR) studies resulted in AZD0284 (), which combined potent inhibition of IL-17A secretion from primary human T17 cells with excellent metabolic stability and good PK in preclinical species.

Discovery of AZD8154, a Dual PI3Kγδ Inhibitor for the Treatment of Asthma.

Starting from our previously described PI3Kγ inhibitors, we describe the exploration of structure-activity relationships that led to the discovery of highly potent dual PI3Kγδ inhibitors. We explored changes in two positions of the molecules, including macrocyclization, but ultimately identified a simpler series with the desired potency profile that had suitable physicochemical properties for inhalation. We were able to demonstrate efficacy in a rat ovalbumin challenge model of allergic asthma and in cells derived from asthmatic patients.

Improving Assessment, Diagnosis, and Management of Urinary Incontinence and Lower Urinary Tract Symptoms on Acute and Rehabilitation Wards That Admit Adult Patients: Protocol for a Before-and-After Implementation Study.

Background: Urinary incontinence (UI) and lower urinary tract symptoms (LUTS) are commonly experienced by adult patients in hospitals (inpatients). Although peak bodies recommend that health services have systems for optimal UI and LUTS care, they are often not delivered. For example, results from the 2017 Australian National Stroke Audit Acute Services indicated that of the one-third of acute stroke inpatients with UI, only 18% received a management plan.

Addressing Sexuality Among People Living With Chronic Disease and Disability: A Systematic Mixed Methods Review of Knowledge, Attitudes, and Practices of Health Care Professionals.

Objective: To systematically review health care professionals' practices and attitudes toward addressing sexuality with people who are living with chronic disease and disability.

Data Sources: Scopus, PubMed, PsycINFO, Cumulative Index to Nursing and Allied Health, Allied and Complementary Medicine Database, and MEDLINE were searched to August 2020 for English language publications. Reference lists of relevant publications were also searched.

The sigma receptor ligand N-phenylpropyl-N'-(4-methoxyphenethyl)3piperazine (YZ-067) enhances the cocaine conditioned-rewarding properties while inhibiting the development of sensitization of cocaine in mice.

Rationale: The N-phenylpropyl-N'-substituted piperazines SA-4503 (N-phenylpropyl-N'-(3,4-dimethoxyphenethyl)piperazine) and YZ-185 (N-phenylpropyl-N'-(3-methoxyphenethyl)piperazine) bind to sigma (σ) receptors and block the development of cocaine-induced conditioned place preference at concentrations that inhibit cocaine-induced hyperactivity. YZ-067 (N-phenylpropyl-N'-(4-methoxyphenethyl)piperazine) also binds to sigma receptors and attenuates cocaine-induced hyperactivity in mice.

Objectives: The present study determined the effect of YZ-067 on the development and expression of cocaine (66 μmol/kg or 33 μmol/kg) conditioned place preference (CPP) and locomotor sensitization in mice.

An Angle on MK2 Inhibition-Optimization and Evaluation of Prevention of Activation Inhibitors.

The mitogen-activated protein kinase p38α pathway has been an attractive target for the treatment of inflammatory conditions such as rheumatoid arthritis. While a number of p38α inhibitors have been taken to the clinic, they have been limited by their efficacy and toxicological profile. A lead identification program was initiated to selectively target prevention of activation (PoA) of mitogen-activated protein kinase-activated protein kinase 2 (MK2) rather than mitogen- and stress-activated protein kinase 1 (MSK1), both immediate downstream substrates of p38α, to improve the efficacy/safety profile over direct p38α inhibition.

Haemostatic Changes in Five Patients Infected with Ebola Virus.

Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were analysed for clotting time, fibrinogen, and D-dimer levels. Plasma from healthy volunteers was also collected by two methods to determine effect of centrifugation on test results as blood collected in Sierra Leone was not centrifuged.

Developing interventions to address sexuality after stroke: Findings from a four-panel modified Delphi study.

Background: Although stroke has a profound impact on sexuality there are limited evidence-based interventions to support rehabilitation professionals in this area. The aim of the current research was to prioritize content areas and approaches to sexual rehabilitation from the perspective of stroke survivors, their partners, stroke rehabilitation clinicians and researchers.

Methods: A 2-step online Delphi method was used to prioritize the content of, and approaches to, sexual rehabilitation with stroke survivors, their partners, stroke rehabilitation clinicians and researchers.

Insights into the nature of female sexuality from the perspective of female stroke survivors.

The purpose of this study was to provide insights into the nature of female sexuality from the perspective of one group of women following a stroke. Nine female stroke survivors from metropolitan and surrounding districts of Sydney, Australia participated in face to face semi-structured interviews about sexuality after stroke. The age of stroke survivors ranged from 31 to 70 years.

How is sexuality after stroke experienced by stroke survivors and partners of stroke survivors? A systematic review of qualitative studies.

Objective:: To synthesise how post-stroke sexuality is experienced by stroke survivors and partners of stroke survivors.

Methods:: MEDLINE, PubMed, SCOPUS, CINAHL and PsycINFO were searched from inception to May 2018 using a combination of relevant Medical Subject Headings and Free Text Terms. Only papers published in English reporting original qualitative research were included.

Analysis and imaging of boron distribution in maize by quantitative neutron capture radiography.

Quantitative neutron capture radiography (QNCR) of B found in pre-dried maize samples has been conducted. Calibration standards constructed from filter paper mimicked plant tissues to reduce confounding matrix effects. A mathematical track elimination method improves the LOD as well as the visual contrast image at low boron concentration levels.

Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors.

In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable for oral administration. Compound 15 was advanced into in vivo studies showing dose-dependent inhibition of LPS-induced airway neutrophilia in rats when administered orally.

Fertility-sparing Surgery for Presumed Early-stage Invasive Cervical Cancer: A Survey of Practice in the United Kingdom.

Aim: To explore current practice in fertility-sparing surgery for cervical cancer in the UK.

Materials And Methods: A web-based structured questionnaire was designed and circulated to all members of the British Gynaecological Cancer Society.

Results: From 111 recipients, a total of 49 responses were collected.

The impact of stroke on female sexuality.

Purpose: The purpose of this study was to explore the impact of stroke on female sexuality from the perspective of women who have had a stroke.

Method: A descriptive qualitative study. Nine female stroke survivors living in metropolitan and surrounding districts of Sydney, Australia took part in semi-structured conversational interviews.

Comparing Brain Morphometry Across Multiple Childhood Psychiatric Disorders.

Objective: In both children and adults, psychiatric illness is associated with structural brain alterations, particularly in the prefrontal cortex (PFC). However, most studies compare gray matter volume (GMV) in healthy volunteers (HVs) to one psychiatric group. We compared GMV among youth with anxiety disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), and HVs.

N-phenylpropyl-N'-substituted piperazines occupy sigma receptors and alter methamphetamine-induced hyperactivity in mice.

This study examined the effect of the N-phenylpropyl-N'-substituted piperazine ligands SA4503 (3.4-dimethoxyphenethyl), YZ-067 (4-methoxyphenethyl), YZ-185 (3-methoxyphenethyl) and Nahas-3h (4-methoxybenzyl) on methamphetamine-induced hyperactivity in mice. In a previous study in rats, SA4503 increased methamphetamine-induced hyperactivity at a lower ligand dose and enhanced it at a higher dose.

Tactics for preclinical validation of receptor-binding radiotracers.

Introduction: Aspects of radiopharmaceutical development are illustrated through preclinical studies of [I]-(E)-1-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-4-(iodoallyl)piperazine ([I]-E-IA-BF-PE-PIPZE), a radioligand for sigma-1 (σ) receptors, coupled with examples from the recent literature. Findings are compared to those previously observed for [I]-(E)-1-(2-(2,3-dimethoxy-5-yl)ethyl)-4-(iodoallyl)piperazine ([I]-E-IA-DM-PE-PIPZE).

Methods: Syntheses of E-IA-BF-PE-PIPZE and [I]-E-IA-BF-PE-PIPZE were accomplished by standard methods.

Spirometer guided chest imaging in children: It is worth the effort!

Purpose: Computed tomography (CT) and magnetic resonance imaging (MRI) scans are used to assess and monitor several pediatric lung diseases. It is well recognized that lung volume at the moment of acquisition has a major impact on the appearance of lung parenchyma and airways. Importantly, the sensitivity of chest CT and MRI to detect bronchiectasis and gas trapping is highly dependent on adequate volume control during the image acquisition.

Aberrant intrinsic functional connectivity within and between corticostriatal and temporal-parietal networks in adults and youth with bipolar disorder.

Background: Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas.

Method: We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10-50 years) with BD (n = 39) and healthy volunteers (HV; n = 78).

Cocaine occupancy of sigma1 receptors and dopamine transporters in mice.

Activation of sigma1 (σ1) receptors contributes to the behavioral and toxic effects of (-)-cocaine. We studied a key step, the ability of (-)-cocaine to occupy σ1 receptors in vivo, using CD-1(®) mice and the novel radioligand [(125) I]E-N-1-(3'-iodoallyl)-N'-4-(3",4"-dimethoxyphenethyl)-piperazine ([(125) I]E-IA-DM-PE-PIPZE). (-)-Cocaine displayed an ED50 of 68 μmol/kg for inhibition of specific radioligand binding in whole brain, with values between 73 and 80 μmol/kg for heart, lung, and spleen.