Intranasal delivery of imaging agents to the brain.

The potential of intranasal administered imaging agents to altogether bypass the blood-brain barrier offers a promising non-invasive approach for delivery directly to the brain. This review provides a comprehensive analysis of the advancements and challenges of delivering neuroimaging agents to the brain by way of the intranasal route, focusing on the various imaging modalities and their applications in central nervous system diagnostics and therapeutics. The various imaging modalities provide distinct insights into the pharmacokinetics, biodistribution, and specific interactions of imaging agents within the brain, facilitated by the use of tailored tracers and contrast agents.

Preparing for the next respiratory pathogen pandemic: using tabletop simulation exercises to strengthen national planning in Cook Islands, Costa Rica, Lebanon and Mongolia.

The Preparedness and Resilience for Emerging Threats (PRET) initiative takes an innovative mode-of-transmission approach to pandemic planning by advocating for integrated preparedness and response systems and capacities for groups of pathogens with common transmission pathways. The World Health Organization (WHO) launched this initiative in 2023 with the publication of PRET Module 1 addressing respiratory pathogens. Exercise PanPRET-1 is a customizable tabletop simulation exercise (TTX) package developed to complement PRET Module 1.

Technetium Nitrido Complexes of Tetradentate Thiosemicarbazones: Kit-Based Radiolabeling, Characterization, and Evaluation.

Bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators have demonstrated utility in nuclear medicine. In particular, the Cu complexes have been extensively developed for hypoxia imaging and molecular imaging of peptide and protein markers of disease. However, the chemistry and application of bis(thiosemicarbazone) and pyridylhydrazone-thiosemicarbazone chelators in combination with Tc, the most widely used radionuclide in nuclear medicine, is underexplored.

Sustaining a therapeutic environment within mental health in-patient settings during COVID-19. Results of a Delphi study.

Aim: Develop a strengths-based, person-centred, trauma-informed and recovery-oriented framework to mitigate any potential increase in conflict resulting from the implementation of C19 restrictions.

Background: Guidance addressing the unique challenges posed by Covid-19 within mental health in-patient settings, including how to support those whose distress may present as behaviour that challenges including violence and self-harm, remains urgently needed.

Methodology/approach: A Delphi design involving four iterative stages was adopted.

Addressing the challenges of implementing evidence-based prioritisation in global health.

Global health requires evidence-based approaches to improve health and decrease inequalities. In a roundtable discussion between health practitioners, funders, academics and policy-makers, we recognised key areas for improvement to deliver better-informed, sustainable and equitable global health practices. These focus on considering information-sharing mechanisms and developing evidence-based frameworks that take an adaptive function-based approach, grounded in the ability to perform and respond to prioritised needs.

Pre-targeting amyloid-β with antibodies for potential molecular imaging of Alzheimer's disease.

With the aim of developing the concept of pretargeted click chemistry for the diagnosis of Alzheimer's disease two antibodies specific for amyloid-β were modified to incorporate -cyclooctene functional groups. Two bis(thiosemicarbazone) compounds with pendant 1,2,4,5-tetrazine functional groups were prepared and radiolabelled with positron emitting copper-64. The new copper-64 complexes rapidly react with the -cyclooctene functionalized antibodies in a bioorthogonal click reaction and cross the blood-brain barrier in mice.

Modern Developments in Bifunctional Chelator Design for Gallium Radiopharmaceuticals.

The positron-emitting radionuclide gallium-68 has become increasingly utilised in both preclinical and clinical settings with positron emission tomography (PET). The synthesis of radiochemically pure gallium-68 radiopharmaceuticals relies on careful consideration of the coordination chemistry. The short half-life of 68 min necessitates rapid quantitative radiolabelling (≤10 min).

A Biodistribution Study of the Radiolabeled Kv1.3-Blocking Peptide DOTA-HsTX1[R14A] Demonstrates Brain Uptake in a Mouse Model of Neuroinflammation.

The voltage-gated potassium channel Kv1.3 regulates the pro-inflammatory function of microglia and is highly expressed in the post-mortem brains of individuals with Alzheimer's and Parkinson's diseases. HsTX1[R14A] is a selective and potent peptide inhibitor of the Kv1.

Hexadentate technetium-99m bis(thiosemicarbazonato) complexes: synthesis, characterisation and biodistribution.

The syntheses of non-oxido/non-nitrido bis(thiosemicarbazonato)technetium(V) complexes featuring a series of alkyl and ether substituents is presented. The bis(thiosemicarbazones) were radiolabelled with technetium-99m using an optimised one-pot synthesis from [Tc][TcO]. Mass spectrometry and computational chemistry data suggested a distorted trigonal prismatic coordination environment for the bis(thiosemicarbazonato)technetium(V) complexes by way of a bis(thiosemicarbazone)technetium(V)-oxido intermediate complex.

A General Design Strategy Enabling the Synthesis of Hydrolysis-Resistant, Water-Stable Titanium(IV) Complexes.

Despite its prevalence in the environment, the chemistry of the Ti ion has long been relegated to organic solutions or hydrolyzed TiO polymorphs. A knowledge gap in stabilizing molecular Ti species in aqueous environments has prevented the use of this ion for various applications such as radioimaging, design of water-compatible metal-organic frameworks (MOFs), and aqueous-phase catalysis applications. Herein, we show a thorough thermodynamic screening of bidentate chelators with Ti in aqueous solution, as well as computational and structural analyses of key compounds.

Does screening or routine enquiry for adverse childhood experiences (ACEs) meet criteria for a screening programme? A rapid evidence summary.

Background: Adverse childhood experiences (ACEs) are traumatic events in childhood that can have impacts throughout life. It has been suggested that ACEs should be 'screened' for, or routinely enquired about, in childhood or adulthood. The aim of this work is to review evidence for this against the United Kingdom National Screening Committee (UKNSC) programme criteria.

The Synthesis of a Bis(thiosemicarbazone) Macrocyclic Ligand and the Mn(II), Co(II), Zn(II) and Ga(III) Complexes.

A 1,4,7,10-tetraazacyclododecane (cyclen) variant bearing two thiosemicarbazone pendant groups has been prepared. The ligand forms complexes with Mn, Co and Zn. X-ray crystallography of the Mn, Co and Zn complexes showed that the ligand provides a six-coordinate environment for the metal ions.

Understanding Home Hemodialysis Patient Attrition: A Cohort Study.

Background: Home hemodialysis (HHD) offers a flexible, patient-centered modality for patients with kidney failure. Growth in HHD is achieved by increasing the number of patients starting HHD and reducing attrition with strategies to prevent the modifiable reasons for loss.

Objective: Our primary objective was to describe a Canadian HHD population in terms of technique failure and time to exit from HHD in order to understand reasons for exit.

Farewell to Professor David Yaffe - A pillar of the myogenesis field.

It is with great sadness that we have learned about the passing of Professor David Yaffe (1929-2020, Israel). Yehi Zichro Baruch - May his memory be a blessing. David was a man of family, science and nature.

An octadentate bis(semicarbazone) macrocycle: a potential chelator for lead and bismuth radiopharmaceuticals.

A variant of 1,4,7,10-tetraazacyclododecane (cyclen) bearing two semicarbazone pendant groups has been prepared. The octadentate ligand forms complexes with Bi3+ and Pb2+. X-ray crystallography showed that the neutral ligand provides an eight-coordinate environment for both metal ions and intermolecular hydrogen bond interactions have influenced the coordination environments of both complexes in the solid state.

Intermittent Parathyroid Hormone Accelerates Stress Fracture Healing More Effectively Following Cessation of Bisphosphonate Treatment.

Parathyroid hormone (PTH) and bisphosphonates (BPs), including alendronate (ALN), have opposing effects on bone dynamics. The extent to which PTH remains effective in the treatment of stress fracture (SFx) in the presence of an ongoing BP treatment has not been tested. SFx was induced in 150 female Wistar rats, divided into five equal groups ( = 30).

Crisis resolution and home treatment in the UK: A survey of model fidelity using a novel review methodology.

Crisis resolution teams (CRTs) provide treatment at home to people experiencing mental health crises, as an alternative to hospital admission. Previous UK research, based on self-report surveys, suggests that a loosely specified model has resulted in wide variations in CRTs' service delivery, organization and outcomes. A fidelity scale (developed through evidence review and stakeholder consensus) provided a means of objectively measuring adherence to a model of good practice for CRTs, via one-day fidelity reviews of UK crisis teams.

A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior.

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study.

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial.

Background: The high-fat ketogenic diet (KD) has become an increasingly popular diet not only in overweight/obese populations, or those with clinical conditions, but also in healthy non-overweight populations.

Objective: Because there are concerns about the association between high-fat diets and cognitive decline, this study aimed to determine the effects of a KD compared with an isocaloric high-carbohydrate, low-fat (HCLF) diet on cognitive function, sleep, and mood in healthy, normal-weight individuals.

Methods: Eleven healthy, normal-weight participants (mean age: 30 ± 9 y) completed this randomized, controlled, crossover study.

Modification of Biodistribution and Brain Uptake of Copper Bis(thiosemicarbazonato) Complexes by the Incorporation of Amine and Polyamine Functional Groups.

The synthesis of new bis(thiosemicarbazonato)copper(II) complexes featuring polyamine substituents via selective transamination reactions is presented. Polyamines of different lengths, with different ionizable substituent groups, were used to modify and adjust the hydrophilic/lipophilic balance of the copper complexes. The new analogues were radiolabeled with copper-64 and their lipophilicities estimated using distribution coefficients.

Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies.

Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting.

Tuning the properties of tris(hydroxypyridinone) ligands: efficient Ga chelators for PET imaging.

The prototype tris(1,6-dimethyl-3-hydroxypyridin-4-one) chelator for gallium-68, THPMe, has shown great promise for rapid and efficient kit-based 68Ga labelling of PET radiopharmaceuticals. Peptide derivatives of THPMe have been used to image expression of their target receptors in vivo in preclinical and clinical studies. Herein we describe new synthetic routes to the THP platform including replacing the 1,6-dimethyl-3-hydroxypyridin-4-one N1-CH3 group of THPMe with O (tris(6-methyl-3-hydroxypyran-4-one, THPO) and N1-H (tris(6-methyl-3-hydroxypyridin-4-one), THPH) groups.