As a result of their unique compositions and properties, nanomaterials have recently seen a tremendous increase in use for novel cancer therapies. By taking advantage of the optical absorption of ...near-infrared light, researchers have utilized nanostructures such as carbon nanotubes, gold nanorods, and graphene oxide sheets to enhance photothermal therapies and target the effect on the tumor tissue. However, new uses for nanomaterials in targeted cancer therapy are coming to light, and the efficacy of photothermal therapy has increased dramatically. In this work, we review some of the current applications of nanomaterials to enhance photothermal therapy, specifically as photothermal absorbers, drug delivery vehicles, photoimmunological agents, and theranostic tools.
Aggregated tau protein is associated with over 20 neurological disorders, which include Alzheimer's disease. Previous work has shown that tau's sequence segments VQIINK and VQIVYK drive its ...aggregation, but inhibitors based on the structure of the VQIVYK segment only partially inhibit full-length tau aggregation and are ineffective at inhibiting seeding by full-length fibrils. Here we show that the VQIINK segment is the more powerful driver of tau aggregation. Two structures of this segment determined by the cryo-electron microscopy method micro-electron diffraction explain its dominant influence on tau aggregation. Of practical significance, the structures lead to the design of inhibitors that not only inhibit tau aggregation but also inhibit the ability of exogenous full-length tau fibrils to seed intracellular tau in HEK293 biosensor cells into amyloid. We also raise the possibility that the two VQIINK structures represent amyloid polymorphs of tau that may account for a subset of prion-like strains of tau.
Genetic factors are recognized to contribute to peptic ulcer disease (PUD) and other gastrointestinal diseases, such as gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS) and ...inflammatory bowel disease (IBD). Here, genome-wide association study (GWAS) analyses based on 456,327 UK Biobank (UKB) individuals identify 8 independent and significant loci for PUD at, or near, genes MUC1, MUC6, FUT2, PSCA, ABO, CDX2, GAST and CCKBR. There are previously established roles in susceptibility to Helicobacter pylori infection, response to counteract infection-related damage, gastric acid secretion or gastrointestinal motility for these genes. Only two associations have been previously reported for duodenal ulcer, here replicated trans-ancestrally. The results highlight the role of host genetic susceptibility to infection. Post-GWAS analyses for PUD, GORD, IBS and IBD add insights into relationships between these gastrointestinal diseases and their relationships with depression, a commonly comorbid disorder.
Antibiotic-resistant bacteria (ARB) present a global public health problem. With numbers of community-acquired resistant infections increasing, understanding the mechanisms by which people are ...exposed to and colonised by ARB can help inform effective strategies to prevent their spread. The role natural environments play in this is poorly understood. This is the first study to combine surveillance of ARB in bathing waters, human exposure estimates and association between exposure and colonisation by ARB in water users.
97 bathing water samples from England and Wales were analysed for the proportion of E. coli harbouring blaCTX-M. These data were used to estimate the likelihood of water users ingesting blaCTX-M-bearing E. coli. Having identified surfers as being at risk of exposure to ARB, a cross-sectional study was conducted. Regular surfers and non-surfers were recruited to assess whether there is an association between surfing and gut colonisation by blaCTX-M-bearing E. coli.
11 of 97 bathing waters sampled were found to contain blaCTX-M-bearing E. coli. While the percentage of blaCTX-M-bearing E. coli in bathing waters was low (0.07%), water users are at risk of ingesting these ARB. It is estimated that over 2.5 million water sports sessions occurred in 2015 resulting in the ingestion of at least one blaCTX-M-bearing E. coli. In the epidemiological survey, 9/143 (6.3%) surfers were colonised by blaCTX-M-bearing E. coli, as compared to 2/130 (1.5%) of non-surfers (risk ratio=4.09, 95% CI 1.02 to 16.4, p=0.046).
Surfers are at risk of exposure to and colonisation by clinically important antibiotic-resistant E. coli in coastal waters. Further research must be done on the role natural environments play in the transmission of ARB.
•E. coli in coastal waters harbour various blaCTX-M genes, which confer resistance to multiple beta-lactam antibiotics.•Surfers are at higher risk of ingesting CTX-M-producing E. coli while surfing than other water users.•Surfers are at a higher risk of being colonised by CTX-M-producing E. coli compared to non-surfers.
A major trade-off of land-use change is the potential for increased risk of infectious diseases, a.o. through impacting disease vector life-cycles. Evaluating the public health implications of ...land-use conversions requires spatially detailed modelling linking land-use to vector ecology. Here, we estimate the impact of deforestation for oil palm cultivation on the number of life-cycle completions of Aedes albopictus via its impact on local microclimates. We apply a recently developed mechanistic phenology model to a fine-scaled (50-m resolution) microclimate dataset that includes daily temperature, rainfall and evaporation. Results of this combined model indicate that the conversion from lowland rainforest to plantations increases suitability for A. albopictus development by 10.8%, moderated to 4.7% with oil palm growth to maturity. Deforestation followed by typical plantation planting-maturation-clearance-replanting cycles is predicted to create pulses of high development suitability. Our results highlight the need to explore sustainable land-use scenarios that resolve conflicts between agricultural and human health objectives.
In insect-pollinated plants, the foraging behavior of pollinators affects their pattern of movement. If distinct bee species vary in their foraging behaviors, different models may best describe their ...movement. In this study, we quantified and compared the fine scale movement of three bee species foraging on patches of Medicago sativa. Bee movement was described using distances and directions traveled between consecutive racemes. Bumble bees and honey bees traveled shorter distances after visiting many flowers on a raceme, while the distance traveled by leafcutting bees was independent of flower number. Transition matrices and vectors were calculated for bumble bees and honey bees to reflect their directionality of movement within foraging bouts; leafcutting bees were as likely to move in any direction. Bee species varied in their foraging behaviors, and for each bee species, we tested four movement models that differed in how distances and directions were selected, and identified the model that best explained the movement data. The fine-scale, within-patch movement of bees could not always be explained by a random movement model, and a general model of movement could not be applied to all bee species.
Learning in a constant environment, and adapting flexibly to a changing one, through changes in reinforcement contingencies or valence-free cues, depends on overlapping circuitry that interconnects ...the prefrontal cortex (PFC) with the striatum and is subject to several forms of neurochemical modulation. We present evidence from recent studies in animals employing electrophysiological, pharmacological and lesion techniques, and neuroimaging, neuropsychological and pharmacological investigations of healthy humans and clinical patients. Dopamine (DA) neurotransmission in the medial striatum and PFC is critical for basic reinforcement learning and the integration of negative feedback during reversal learning, whilst orbitofrontal 5-hydroxytryptamine (5-HT) likely mediates this type of low level flexibility, perhaps by reducing interference from salient stimuli. The role of prefrontal noradrenaline (NA) in higher order flexibility indexed through attentional set-shifting has recently received significant empirical support, and similar avenues appear promising in the field of task switching.
The COVID-19 pandemic has led to dramatic social and economic changes in daily life. First studies report an impact on mental health of the general population showing increased levels of anxiety, ...stress and depression. In this study, we compared the impact of the pandemic on two culturally and economically similar European countries: the UK and Germany.
Participants (UK = 241, German = 541) completed an online-survey assessing COVID-19 exposure, impact on financial situation and work, substance and media consumption, mental health using the Symptom-Check-List-27 (SCL-27) and the Schizotypal Personality Questionnaire.
We found distinct differences between the two countries. UK responders reported a stronger direct impact on health, financial situation and families. UK responders had higher clinical scores on the SCL-27, and higher prevalence. Interestingly, German responders were less hopeful for an end of the pandemic and more concerned about their life-stability.
As 25% of both German and UK responders reported a subjective worsening of the general psychological symptoms and 20-50% of German and UK responders reached the clinical cut-off for depressive and dysthymic symptoms as well as anxieties, it specifically shows the need for tailored intervention systems to support large proportions of the general public.
Biofilm formation is a major virulence factor contributing to the chronicity of infections. To date few studies have evaluated biofilm formation in infecting isolates of patients including both ...Gram-positive and Gram-negative multidrug-resistant (MDR) species in the context of numerous types of infectious syndromes. Herein, we investigated the biofilm forming capacity in a large collection of single patient infecting isolates and compared the relationship between biofilm formation to various strain characteristics.
The biofilm-forming capacity of 205 randomly sampled clinical isolates from patients, collected from various anatomical sites, admitted for treatment at Brooke Army Medical Center (BAMC) from 2004-2011, including methicillin-resistant/methicillin susceptible Staphylococcus aureus (MRSA/MSSA) (n=23), Acinetobacter baumannii (n=53), Pseudomonas aeruginosa (n=36), Klebsiella pneumoniae (n=54), and Escherichia coli (n=39), were evaluated for biofilm formation using the high-throughput microtiter plate assay and scanning electron microscopy (SEM). Relationships between biofilm formation to clonal type, site of isolate collection, and MDR phenotype were evaluated. Furthermore, in patients with relapsing infections, serial strains were assessed for their ability to form biofilms in vitro.
Of the 205 clinical isolates tested, 126 strains (61.4%) were observed to form biofilms in vitro at levels greater than or equal to the Staphylococcus epidermidis, positive biofilm producing strain, with P. aeruginosa and S. aureus having the greatest number of biofilm producing strains. Biofilm formation was significantly associated with specific clonal types, the site of isolate collection, and strains positive for biofilm formation were more frequently observed to be MDR. In patients with relapsing infections, the majority of serial isolates recovered from these individuals were observed to be strong biofilm producers in vitro.
This study is the first to evaluate biofilm formation in a large collection of infecting clinical isolates representing diverse types of infections. Our results demonstrate: (1) biofilm formation is a heterogeneous property amongst clinical strains which is associated with certain clonal types, (2) biofilm forming strains are more frequently isolated from non-fluid tissues, in particular bone and soft tissues, (3) MDR pathogens are more often biofilm formers, and (4) strains from patients with persistent infections are positive for biofilm formation.
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