A grabby substrate: A 3D nanostructured substrate, namely, a silicon-nanopillar (SiNP) array coated with epithelial-cell adhesion-molecule antibody (anti-EpCAM), shows enhanced local topographic interactions between nanoscale cell-surface components and the substrates surface, resulting in enhanced cell-capture efficiency when employed to isolate viable cancer cells from whole-blood samples (see schematic and SEM image of a captured cancer cell).
To investigate ten year trends in folate status in Taiwanese aged >=19 yrs by three Nutrition and Health Survey in Taiwan (NAHSIT) in 1993-1996, 1999-2000 and 2005-2008. Women had higher blood folate levels than men in all three surveys. The prevalence of folate deficiency (5.2% <3 ng/mL) and insufficiency (34.1% <=6 ng/mL) in men was highest in 2005-2008. Adults aged 19-30 yrs had the lowest blood levels and the highest prevalence of deficiency (8.1% in men; 3.5% in women) and insufficiency (48.6% in men; 25% in women) as compared to other age groups in 2005-2008. Folate insufficiency rate in those aged 31-44 yrs was twice as high in men and three times as high in women in 2005-2008 compared to 1993-1996. In the elderly, folate insufficiency rate (28%) in 2005-2008 was not higher than that of 1993-1996, although it was higher than that found in 1999-2000 (18.4%). Men aged >=80 yrs had the poorest folate status in 2005-2008, and men were twice as likely to have inadequate status as women. Plasma homocysteine (Hcy) levels were higher in older men than older women in both surveys. The elderly had significantly higher plasma tHcy in 2005-2008 compared to the 1999-2000 survey. Dark green vegetables and fruit intake frequency in young adults (19-30 yrs) was the lowest among all age groups. This study suggests that folate status in Taiwan has not improved during the past fifteen years, and has worsened in the young population.
Brensocatib is a novel, oral, selective, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), which activates several neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG) in the bone marrow during the early stage of neutrophil maturation. These NSPs are associated with pathogen destruction and inflammatory mediation; their dysregulated activation can result in excess secretion of active NSPs causing damaging inflammation and contributing to neutrophil-mediated inflammatory and autoimmune diseases. Pharmacological inhibition of DPP1 in the bone marrow could therefore represent an attractive strategy for these neutrophil-driven diseases. A completed Phase 2 trial in non-cystic fibrosis bronchiectasis patients (ClinicalTrials.gov number NCT03218917; EudraCT number: 2017-002533-32) indeed demonstrated that administration of brensocatib attenuated the damaging effects of chronic inflammation by inhibiting the downstream activation of NSPs. To support a range of preclinical programs and further understand how rodent species and strains may affect brensocatib’s pharmacokinetic (PK) profile and its pharmacodynamic (PD) effects on NE, PR3, and CatG, an extensive naïve dosing study with brensocatib at different dosing levels, frequencies, and durations was undertaken. Dose-dependent PK exposure responses (AUC and Cmax) were observed regardless of the rodent species and strain. Overall, mice showed greater reduction in NSP activities compared to rats. Both mice and rats dosed once daily (QD) had equivalent NSP activity reduction compared to BID (twice a day) dosing when the QD dose was 1.5-times the BID daily dose. For both mouse strains, CatG activity was reduced the most, followed by NE, then PR3; whereas, for both rat strains, PR3 activity was reduced the most, followed by CatG, and then NE. Maximum reduction in NSP activities was observed after ∼7 days and recoveries were nearly symmetrical. These results may facilitate future in vivo brensocatib study dosing considerations, such as the timing of prophylactic or therapeutic administration, choice of species, dosage and dosing frequency.
Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA both in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure.
Laser-triggered nanobomb: Size-controlled gold supramolecular nanoparticles (Au-SNPs) were synthesized from 2 nm gold colloids by a supramolecular self-assembly approach. These Au-SNPs exhibited significantly enhanced photothermal effects and could be used in conjunction with laser irradiation for the selective destruction of cancer cells (see picture) after the incorporation of a target-specific ligand. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
To evaluate the outcome of twin–twin transfusion syndrome (TTTS) treated by fetoscopic laser therapy (FLT) stratified by Quintero staging. A total of 100 TTTS cases treated by FLT, from October 2005 to August 2014, were included in this study. Cases were divided into first and second half periods to evaluate the learning effect-related outcomes, and logistic regression was applied to determine the independent factors in predicting the perinatal outcomes. The total fetal survival rate was 68.5%, two fetal survival rate was 55%, and at least one fetal survival rate was 82%. High Quintero stage (Stages III and IV) and small gestational age at delivery were two independent factors predicting lower two fetal survivals. Gestational age at delivery was the only independent factor predicting at least one survival. The odds ratios of high Quintero stage predicting lower two fetal survivals were 11.3 (p < 0.001) and 4.8 (p = 0.043) in the first and second periods, respectively. High Quintero stage and small gestational age at delivery were associated with low two survival rate in TTTS treated by FLT; after gaining experience with FLT, the effect of high Quintero stage on lower two survival rate would decrease.
Abstract Mitochondrial function declines with age, and many pathological processes in neurodegenerative diseases stem from this dysfunction when mitochondria fail to produce the necessary energy required. Photobiomodulation (PBM), long‐wavelength light therapy, has been shown to rescue mitochondrial function in animal models and improve human health, but clinical uptake is limited due to uncertainty around efficacy and the mechanisms responsible. Using 31 P magnetisation transfer magnetic resonance spectroscopy (MT‐MRS) we quantify, for the first time, the effects of 670 nm PBM treatment on healthy ageing human brains. We find a significant increase in the rate of ATP synthase flux in the brain after PBM in a cohort of older adults. Our study provides initial evidence of PBM therapeutic efficacy for improving mitochondrial function and restoring ATP flux with age, but recognises that wider studies are now required to confirm any resultant cognitive benefits.
A supramolecular approach has been developed for the preparation of supramolecular nanoparticles (SNPs) with variable sizes (30-450 nm) from three different molecular building blocks using a cyclodextrin/adamantane recognition system. Positron emission tomography (PET) was employed to study the biodistribution and lymph node drainage of the SNPs in mice. The sizes of the SNPs affect their in vivo characteristics (see picture).
Although nutrient deficiencies are thought to play roles in the development of depression, observational studies have yielded inconsistent results. This study aimed to investigate whether multiple marginal nutrient deficiencies are associated with symptoms of depression in community-dwelling older Taiwanese. Data from 1371 elderly adults recruited from the Elderly Nutrition and Health Survey in Taiwan was used in this study. Depressive symptom scores on depressed mood and emotions affecting daily life were derived from the Medical Outcomes Study Short Form-36 (SF-36). Hemoglobin, serum ferritin, plasma vitamins B 6 , B 12 , and folate concentration, and erythrocyte transketolase and glutathione reductase activation coefficients were measured. After adjusting for age, gender, cognitive function, physical activity, disease history, and medication in the multivariate analysis, anemia, and marginal B 6 deficiency were significantly associated with the presence of depression symptoms, respectively. In addition, co-occurrence of vitamin B 6 with low folate level and co-occurrence of anemia either with low vitamin B 6 or with folate level were all associated with the depressive mood and with depressive emotions defined by SF-36 (odds ratios [OR] in the range of 2.32−7.13, all P values ≤.05). The magnitude of the ORs is larger when the number of deficiencies increased. Elderly people with coexisting marginal deficiencies of nutrients involved in the S-adenosylmethionine and hemoglobin production were more likely to experience depressed mood and emotion that affect daily activity. Examining status of these nutrients is worthy of consideration for older adults with depressed symptoms.
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