Magnetoresponsive liposomes applications in nanomedicine: A comprehensive review.

Safe and effective cancer therapy requires a suitable nanocarrier that can target particular sites, such as cancer cells, in a selective manner. With the tremendous growth in nanotechnology, liposomes, among various competing nanocarriers, have shown promising advances in cancer therapy. Magnetic nanoparticles and metal ions are wide-reaching candidates for conferring magnetic properties and for incorporation into liposomes.

Nanoscale synchrotron x-ray analysis of intranuclear iron in melanised neurons of Parkinson's substantia nigra.

Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson's disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Animal models of Parkinson's have evidenced iron loading inside the nucleoli of nigral neurons, however the nature of intranuclear iron deposition in the melanised neurons of the human substantia nigra is not understood.

Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues.

The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer's disease. Altered metabolism of essential biometals is another feature of Alzheimer's, with amyloid plaques representing sites of disturbed metal homeostasis. Despite these observations, metal-targeting disease treatments have not been therapeutically effective to date.

Preparing Future Surgeons: An Evaluation of Academic Surgeons' Views on Laparoscopic Simulation Training for Medical Students.

Introduction With the development of laparoscopic simulation, medical students are motivated to expand their knowledge and proficiency in basic surgical skills. This study aims to demonstrate their capability and readiness for surgical clerkships and, ultimately, surgical residency. This study's primary objective is to ascertain academic surgeons' perspectives regarding laparoscopic simulation in undergraduate medical education and to determine if early exposure may afford medical students additional opportunities during their surgical clerkships.

Increasing Prevalence of Pediatric Community-acquired UTI by Extended Spectrum β-Lactamase-producing E. coli: Cause for Concern.

Background: Antimicrobial resistance and emerging spectrum-β-lactamase (ESBL) infections are a rising concern in public health. Despite the increasing prevalence of community-acquired (CA) ESBL-E. coli UTIs, there is little data on the antibiotic resistance profiles of this bacterial strain in the pediatric population.

Incidence of Emergency Department Presentations of Symptomatic Stone Disease in Pediatric Patients: A Southeastern Study.

Background The incidence of nephrolithiasis during childhood has increased significantly over recent decades. Some studies indicate a rapid rise in adolescents, particularly in African American women. This study serves to identify trends in symptomatic pediatric nephrolithiasis presentations to the emergency department (ED) as a result of increasing incidence and to determine associations between demographic variables at our single-site tertiary pediatric hospital in the Southeast United States.

Risk factors for community acquired pediatric urinary tract infection with extended-spectrum-β-lactamase Escherichia coli - A case-control study.

Introduction: Community-acquired (CA) infections caused by extended-spectrum β-lactamase (ESBL) producing Escherichia coli urinary tract infections (UTI) have become increasingly prevalent, posing a serious threat to public health. Risk factors for ESBL UTI have not been extensively studied in the pediatric population. We report findings from a case control study to identify risk factors for CA ESBL-producing E.

Effective R relaxation rate, derived from dual-contrast fast-spin-echo MRI, enables detection of hemisphere differences in iron level and dopamine function in Parkinson's disease and healthy individuals.

Background: Clinical estimates of brain iron concentration are achievable with quantitative transverse relaxation rate R, via time-consuming multiple spin-echo (SE) sequences. The objective of this study was to investigate whether quantitative iron-sensitive information may be derived from 3.0 T dual-contrast fast-spin-echo (FSE) sequences (typically employed in anatomical non-quantitative evaluations), as a routinely-collected alternative to evaluate iron levels in healthy (HC) and Parkinson's disease (PD) brains.

A Systematic Review and Meta-Analysis of Cerebrospinal Fluid Amyloid and Tau Levels Identifies Mild Cognitive Impairment Patients Progressing to Alzheimer's Disease.

Reported levels of amyloid-beta and tau in human cerebrospinal fluid (CSF) were evaluated to discover if these biochemical markers can predict the transition from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD). A systematic review of the literature in PubMed and Web of Science (April 2021) was performed by a single researcher to identify studies reporting immunologically-based (xMAP or ELISA) measures of CSF analytes Aβ(1-42) and/or P-tau and/or T-tau in clinical studies with at least two timepoints and a statement of diagnostic criteria. Of 1137 screened publications, 22 met the inclusion criteria for CSF Aβ(1-42) measures, 20 studies included T-tau, and 17 included P-tau.

Making large-scale surgical trials possible: collaboration and the role of surgical trainees.

Background: Recruitment to surgical randomised controlled trials (RCTs) can be challenging. The Sunflower study is a large-scale multi-centre RCT that seeks to establish the clinical and cost effectiveness of pre-operative imaging versus expectant management in patients with symptomatic gallstones undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones. Trials such as Sunflower, with a large recruitment target, rely on teamworking.

Randomised controlled trial to establish the clinical and cost-effectiveness of expectant management versus preoperative imaging with magnetic resonance cholangiopancreatography in patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones (The Sunflower Study): a study protocol.

Introduction: Surgery to remove the gallbladder (laparoscopic cholecystectomy (LC)) is the standard treatment for symptomatic gallbladder disease. One potential complication of gallbladder disease is that gallstones can pass into the common bile duct (CBD) where they may remain dormant, pass spontaneously into the bowel or cause problems such as obstructive jaundice or pancreatitis. Patients requiring LC are assessed preoperatively for their risk of CBD stones using liver function tests and imaging.

Biogenic metallic elements in the human brain?

The chemistry of copper and iron plays a critical role in normal brain function. A variety of enzymes and proteins containing positively charged Cu, Cu, Fe, and Fe control key processes, catalyzing oxidative metabolism and neurotransmitter and neuropeptide production. Here, we report the discovery of elemental (zero-oxidation state) metallic Cu accompanying ferromagnetic elemental Fe in the human brain.

The Individualized Addictions Consultation Team Residential Program: A Creative Solution for Integrating Care for Veterans With Substance Use Disorders Too Complex for Other Residential Treatment Programs.

The Veterans Affairs (VA) healthcare system is one of the main providers of substance use treatment within the United States, and many veterans with a substance use disorder (SUD) present with co-occurring diagnoses or other concerns. Though there has been increasing recognition of the need for integration of treatments for SUD and comorbid mental illness, there have been limited studies of such programs, particularly within the VA healthcare system. To address that gap in the literature, this paper examines treatment outcomes in an integrated model of dual diagnosis residential treatment for veterans: the Individualized Addictions Consultation Team (I-ACT) program.

Cu(III)-bis-thiolato complex forms an unusual mono-thiolato Cu(III)-peroxido adduct.

The stable complex [bis(toluene-3,4-dithiolato)copper(iii)][NEt3H] has been synthesised and characterised as a square-planar Cu(iii) complex by X-ray photoelectron spectroscopy, cyclic voltammetry and DFT calculations. Intriguingly, when fragmented in FTICR-MS, an unusual [(toluene-3,4-dithiolate)Cu(iii)(peroxide)]- complex is formed by reaction with oxygen. Natural 1,2-dithiolenes known to bind molybdenum might stabilise Cu(iii) in vivo.

Regional segmentation strategy for DTI analysis of human corpus callosum indicates motor function deficit in mild cognitive impairment.

Background: The corpus callosum is the largest white matter tract in the human brain, involved in inter-hemispheric transfer and integration of lateralised visual, sensory-motor, language, and cognitive information. Microstructural alterations are implicated in ageing as well as various neurological conditions.

New Method: Cross-sectional diffusion-weighted images of 107 healthy adults were used to create a linear regression model of the ageing corpus callosum and its sub-regions to evaluate the impact of analysis by sub-region, and to test for deviations from healthy ageing parameters in 28 subjects with mild cognitive impairment (MCI).

Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42).

Atypical low-oxidation-state iron phases in Alzheimer's disease (AD) pathology are implicated in disease pathogenesis, as they may promote elevated redox activity and convey toxicity. However, the origin of low-oxidation-state iron and the pathways responsible for its formation and evolution remain unresolved. Here we investigate the interaction of the AD peptide β-amyloid (Aβ) with the iron storage protein ferritin, to establish whether interactions between these two species are a potential source of low-oxidation-state iron in AD.

Analysis of neuronal iron deposits in Parkinson's disease brain tissue by synchrotron x-ray spectromicroscopy.

Background: Neuromelanin-pigmented neurons, which are highly susceptible to neurodegeneration in the Parkinson's disease substantia nigra, harbour elevated iron levels in the diseased state. Whilst it is widely believed that neuronal iron is stored in an inert, ferric form, perturbations to normal metal homeostasis could potentially generate more reactive forms of iron capable of stimulating toxicity and cell death. However, non-disruptive analysis of brain metals is inherently challenging, since use of stains or chemical fixatives, for example, can significantly influence metal ion distributions and/or concentrations in tissues.

The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization.

The α-synuclein (αSN) amyloid fibrillization process is known to be a crucial phenomenon associated with neuronal loss in various neurodegenerative diseases, most famously Parkinson's disease. The process involves different aggregated species and ultimately leads to formation of β-sheet rich fibrillar structures. Despite the essential role of αSN aggregation in the pathoetiology of various neurological disorders, the characteristics of various assemblies are not fully understood.

Label-Free Nanoimaging of Neuromelanin in the Brain by Soft X-ray Spectromicroscopy.

A hallmark of Parkinson's disease is the death of neuromelanin-pigmented neurons, but the role of neuromelanin is unclear. The in situ characterization of neuromelanin remains dependent on detectable pigmentation, rather than direct quantification of neuromelanin. We show that direct, label-free nanoscale visualization of neuromelanin and associated metal ions in human brain tissue can be achieved using synchrotron scanning transmission x-ray microscopy (STXM), through a characteristic feature in the neuromelanin x-ray absorption spectrum at 287.

Metallic iron in cornflakes.

Iron is an essential element, and cornflake-style cereals are typically fortified with iron to a level up to 14 mg iron per 100 g. Even single cornflakes exhibit magnetic behaviour. We extracted iron microparticles from samples of two own-brand supermarket cornflakes using a strong permanent magnet.

Emerging Approaches to Investigate the Influence of Transition Metals in the Proteinopathies.

Transition metals have essential roles in brain structure and function, and are associated with pathological processes in neurodegenerative disorders classed as proteinopathies. Synchrotron X-ray techniques, coupled with ultrahigh-resolution mass spectrometry, have been applied to study iron and copper interactions with amyloid β (1-42) or α-synuclein. Ex vivo tissue and in vitro systems were investigated, showing the capability to identify metal oxidation states, probe local chemical environments, and localize metal-peptide binding sites.

Impact of Autophagy and Aging on Iron Load and Ferritin in Brain.

Biometals such as iron, copper, potassium, and zinc are essential regulatory elements of several biological processes. The homeostasis of biometals is often affected in age-related pathologies. Notably, impaired iron metabolism has been linked to several neurodegenerative disorders.

Metal Ion Binding to the Amyloid β Monomer Studied by Native Top-Down FTICR Mass Spectrometry.

Native top-down mass spectrometry is a fast, robust biophysical technique that can provide molecular-scale information on the interaction between proteins or peptides and ligands, including metal cations. Here we have analyzed complexes of the full-length amyloid β (1-42) monomer with a range of (patho)physiologically relevant metal cations using native Fourier transform ion cyclotron resonance mass spectrometry and three different fragmentation methods-collision-induced dissociation, electron capture dissociation, and infrared multiphoton dissociation-all yielding consistent results. Amyloid β is of particular interest as its oligomerization and aggregation are major events in the etiology of Alzheimer's disease, and it is known that interactions between the peptide and bioavailable metal cations have the potential to significantly damage neurons.